ELEVATED ALT AND AST IN AN ASYMPTOMATIC PERSON

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KEW ST

2009-01-01

Full Text Available -Abnormal liver function test with raised alanine aminotransferase (ALT and raised aspartate aminotransferase (AST are commonly seen in primary care setting. -Chronic alcohol consumption, drugs, non-alcoholic steatohepatitis (NASH and chronic viral hepatitis are common causes associated with raised ALT and AST. -In chronic viral hepatitis, the elevation of liver enzyme may not correlate well with the degree of liver damage. -Non-hepatic causes of raised ALT and AST include polymyositis, acute muscles injury, acute myocardial infarction and hypothyroidism. -In the primary care setting, the doctor should obtain a complete history regarding the risk factors for viral hepatitis, substance abuse and request investigations accordingly. -Suspected chronic viral hepatitis and liver cirrhosis are best referred to hepatologist for further management.

Factors affecting the purpose suppressive antiviral therapy for patients with recurrent genital herpes

Directory of Open Access Journals (Sweden)

I. S. Коlova

2017-01-01

Full Text Available Objective: To study the factors that influence the destination of suppressive antiviral therapy in patients with recurrent genital herpes doctors of different specialties.Material and Methods: The study was conducted based on an anonymous survey of professionals providing medical care to patients with genital herpes. The survey involved 67 experts – 44 dermatologist, 13 obstetricians and 10 urologists working in Skin and Venereal Diseases, Women’s consuitation post and Saint Petersburg clinics.Results: Most respondents indicated that among patients with genital herpes, seeking an appointment, dominated by patients with relapsing nature of the disease. Suppressive antiviral therapy is recommended 68,7% of specialists, including dermatologists 61,3%, 84,6% of obstetricians and gynecologists, and 80% of urologists. The main indications for its experts consider high frequency of relapses, the patient’s tendency to promiscuity, the desire of the patient with fewer relapses, and the emotional response of the patient for the presence of the disease. Do not prescribe suppressive therapy for recurrent genital herpes 31,4% of the doctors surveyed. Among the reasons for which are not appointed by the type of treatment, the patient is dominated by the rejection of this type of treatment, the lack of experience of the destination suppressive therapy, as well as the uncertainty of specialists in its effectiveness.Conclusion: Suppressive antiviral therapy is recommended 68,7% of specialists. Do not prescribe this type of treatment for recurrent genital herpes 31,4% of the doctors surveyed. The proportion of professionals who refuse the appointment of suppressive antiviral therapy, the highest among dermatologists (38,7% compared with 15,4% among obstetricians and 20% of urologists. The most frequent grounds for refusal from this type of treatment is the lack of confidence in its effectiveness. 

Malaria in immuno-suppressed individuals on antiretroviral therapy ...

African Journals Online (AJOL)

Malaria in immuno-suppressed individuals on antiretroviral therapy (ART) in north-central Nigeria. C.R. Pam, B.T. Abubakar, G.O. Inwang, G.A. Amuga. Abstract. The immune deficiency caused by HIV infection reduces the immune response to malaria parasitaemia and therefore leads to an increased frequency of clinical ...

Pattern of AST and ALT changes in Relation to Hemolysis in sickle cell Disease

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K. Nsiah

2011-01-01

Full Text Available Background Elevated aminotransferase levels are commonly associated with compromised hepatic integrity from various insults. In sickle cell disease, aspartate transaminase (AST is also released via intravascular hemolysis. This study was done to determine the pattern of changes in AST and alanine transaminase (ALT, in particular the AST:ALT ratio, and to relate these to the hemolytic state, which we consider to be more important than hepatic and cardiac dysfunction in some individuals with sickle cell disease. Methods Serum aminotransferase levels were measured in 330 subjects with sickle cell disease, as well as hemoglobin, reticulocytes, and lactate dehydrogenase. The AST:ALT ratio was designated as a hemolytic marker, and simple and multivariate regression analyses were carried out between this ratio and other hemolytic markers. Results Mean AST and ALT levels were 48.24 % 27.78 and 26.48 % 22.73 U/L, respectively. However, for 49 subjects without sickle cell disease, mean AST and ALT levels were the same, ie, 23.0 U/L. In the subjects with sickle cell disease, the increases in AST levels were far higher than for ALT, supporting its release via intravascular hemolysis. In 95.8% of the subjects with sickle cell disease, the AST:ALT ratio was > 1, but our results did not suggest overt malfunctioning of the liver and heart in the majority of subjects. Conclusion Regression analyses support the use of the AST:ALT ratio as a hemolytic marker, because it has an inverse association with the hemoglobin level. Whether in steady state or in crisis, provided hepatic and cardiac integrity has not been compromised, subjects with sickle cell disease would have higher AST levels due to the hemolytic nature of the condition. This is the first report highlighting the AST:ALT ratio in sickle cell disease.

A new method for synthesis of As-Te chalcogenide films

Science.gov (United States)

Mochalov, Leonid; Nezhdanov, Aleksey; Usanov, Dmitry; Markelov, Aleksey; Trushin, Vladimir; Chidichimo, Giuseppe; De Filpo, Giovanni; Gogova, Daniela; Mashin, Aleksandr

2017-11-01

A novel Plasma Enhanced Chemical Vapor Deposition method for synthesis of amorphous AsxTe100-x (31 ≤ x ≤ 49) films is demonstrated. The innovative process has been developed in a non-equilibrium low-temperature argon plasma under reduced pressure, employing for the first time volatile As and Te as precursors. Utilization of inorganic precursors, in contrast to the typically used in CVD metal-organic precursors, has given us the chance to achieve ≿halcogenide As-Te films of very high quality and purity. Phase and structural evolution of the As-Te system, based on equilibrium coexistence of two phases (AsTe and As2Te3) has been studied. The dependence of structure and optical bandgap of the chalcogenide materials on their composition was established. The newly developed process is cost-effective and enables deposition of As-Te films with a thickness ranging from 10 nm to 10 μm, the latter is highly desireable for one-mode planar waveguides applications and in other components of integral optics.

Basic design decisions for advanced AST-type NHRs

International Nuclear Information System (INIS)

Gureyeva, L.V.; Egorov, V.V.; Malamud, V.A.

1997-01-01

On the basis of the AST-500 reference design decisions and of the experience gained in the RF during the pilot NDHPs development and construction, the advanced NHR AST-500M has been developed recently by OKB Mechanical Engineering, as well as a whole series of heating and co-generation reactor plants of various unit power. All the designs represent enhanced safety reactor plants meeting the contemporary national requirements and international recommendations for nuclear plants of the new generation. The main objectives for the advanced NHR development are considered. New design decisions and engineering improvements are described briefly. (author). 3 refs, 4 figs

Basic design decisions for advanced AST-type NHRs

Energy Technology Data Exchange (ETDEWEB)

Gureyeva, L V; Egorov, V V; Malamud, V A [OKBM, Nizhny Novgorod (Russian Federation)

1997-09-01

On the basis of the AST-500 reference design decisions and of the experience gained in the RF during the pilot NDHPs development and construction, the advanced NHR AST-500M has been developed recently by OKB Mechanical Engineering, as well as a whole series of heating and co-generation reactor plants of various unit power. All the designs represent enhanced safety reactor plants meeting the contemporary national requirements and international recommendations for nuclear plants of the new generation. The main objectives for the advanced NHR development are considered. New design decisions and engineering improvements are described briefly. (author). 3 refs, 4 figs.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients

DEFF Research Database (Denmark)

Lødrup, A; Pottegård, A; Hallas, J

2015-01-01

BACKGROUND: Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. AIM: To determine the use of proton pump...... inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. METHODS: A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients......, the Danish National Prescription Register, and the Danish Person Register. RESULTS: The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery...

Dosimetric impact of a CT metal artefact suppression algorithm for proton, electron and photon therapies

International Nuclear Information System (INIS)

Wei Jikun; Sandison, George A; Hsi, W-C; Ringor, Michael; Lu Xiaoyi

2006-01-01

Accurate dose calculation is essential to precision radiation treatment planning and this accuracy depends upon anatomic and tissue electron density information. Modern treatment planning inhomogeneity corrections use x-ray CT images and calibrated scales of tissue CT number to electron density to provide this information. The presence of metal in the volume scanned by an x-ray CT scanner causes metal induced image artefacts that influence CT numbers and thereby introduce errors in the radiation dose distribution calculated. This paper investigates the dosimetric improvement achieved by a previously proposed x-ray CT metal artefact suppression technique when the suppressed images of a patient with bilateral hip prostheses are used in commercial treatment planning systems for proton, electron or photon therapies. For all these beam types, this clinical image and treatment planning study reveals that the target may be severely underdosed if a metal artefact-contaminated image is used for dose calculations instead of the artefact suppressed one. Of the three beam types studied, the metal artefact suppression is most important for proton therapy dose calculations, intermediate for electron therapy and least important for x-ray therapy but still significant. The study of a water phantom having a metal rod simulating a hip prosthesis indicates that CT numbers generated after image processing for metal artefact suppression are accurate and thus dose calculations based on the metal artefact suppressed images will be of high fidelity

Kirjavahetus Kaarel Robert Pustaga / Karl Ast Rumor

Index Scriptorium Estoniae

Rumor, Karl, pseud., 1886-1971

2009-01-01

Kirjavahetus Rio de Janeiros elava Karl Ast Rumori ja New Yorgis elava Kaarel Robert Pusta vahel Eesti kongressi kokkukutsumise vajalikkuse, väliseesti ühingute ja nõukogude, ajakirjanduse ning üldise poliitilise olukorra teemadel

Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo

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Yun-Ho Hwang

2018-03-01

Full Text Available Osteoporosis is characterized by a reduction of the bone mineral density (BMD and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP activity. The bone mineral density (BMD and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT c1, dendritic cell-specific transmembrane protein (DC-STAMP, TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs. Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis.

AGS Spallation Target Experiment (ASTE) Collaboration

International Nuclear Information System (INIS)

Oyama, Yukio

1999-01-01

An experiment on mercury spallation target with high energy proton beam, called as the AGS Spallation Target Experiment (ASTE) Collaboration, has been performed at Alternating Gradient Synchrotron (AGS) of Brookhaven National Laboratory (BNL) in USA, in cooperation among the laboratories in Japan, Europe and USA. The experimental setup, scope and preliminary results are presented in the paper. (author)

Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

Science.gov (United States)

Elkind-Hirsch, K E; Anania, C; Malinak, R

1996-09-01

To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

Biodegradation of Chlorpyrifos by Pseudomonas Resinovarans Strain AST2.2 Isolated from Enriched Cultures.

OpenAIRE

Anish Sharma*,; Jyotsana Pandit; Ruchika Sharma and; Poonam Shirkot

2016-01-01

A bacterial strain AST2.2 with chlorpyrifos degrading ability was isolated by enrichment technique from apple orchard soil with previous history of chlorpyrifos use. Based on the morphological, biochemical tests and 16S rRNA sequence analysis, AST2.2 strain was identified as Pseudomonas resinovarans. The strain AST2.2 utilized chlorpyrifos as the sole source of carbon and energy. This strain exhibited growth upto 400mg/l concentration of chlorpyrifos and exhibited high extracellular organopho...

Precision holography for N={2}^{\\ast } on S 4 from type IIB supergravity

Science.gov (United States)

Bobev, Nikolay; Gautason, Friðrik Freyr; van Muiden, Jesse

2018-04-01

We find a new supersymmetric solution of type IIB supergravity which is holographically dual to the planar limit of the four-dimensional N={2}^{\\ast } supersymmetric Yang-Mills theory on S 4. We study a probe fundamental string in this background which is dual to a supersymmetric Wilson loop in the N={2}^{\\ast } theory. Using holography we calculate the expectation value of this line operator to leading order in the 't Hooft coupling. The result is a non-trivial function of the mass parameter of the N={2}^{\\ast } theory that precisely matches the result from supersymmetric localization.

Mindfulness-based cognitive therapy for depressed individuals improves suppression of irrelevant mental-sets.

Science.gov (United States)

Greenberg, Jonathan; Shapero, Benjamin G; Mischoulon, David; Lazar, Sara W

2017-04-01

An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis.

Science.gov (United States)

Laurent, Irakoze; Tang, Siying; Astère, Manirakiza; Wang, Kan Ran; Deng, Shuhua; Xiao, Ling; Li, Qi Fu

2018-03-23

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis. Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59, -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = -3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06). Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

Safety Assessment for transient event occurred during the ASTS test of Hanbit Unit 2

International Nuclear Information System (INIS)

Yang, Changkeun; Kim, Yohan; Ha, Sangjun

2014-01-01

Safety Injection has been actuated during the ASTS (Automatic Seismic Trip System) test of Hanbit Unit 2 on Feb. 28, 2014. It could be bad effect on system integrity. KHNP has been performed safety assessment of system for effect of Safety Injection (SI) actuation occurred during the ASTS test of hanbit Unit 2. Stable state of nuclear power plant system has been confirmed according to Safety Injection and reactor trip event occurred during the ASTS test of hanbit Unit 2. In the result of system safety assessment, major variables of nuclear power plant are located in optimal range and not exceed safety limit. It remains nuclear fuel and the integrity of the power plant is in a safe condition were conformed. After ASTS action, thermal elimination has been processed throughout the turbine until turbine signal occurrence because ASTS is connected to M-G set in the present hanbit Unit 2. Therefore, Safety Injection signal has been actuated by rapid reduction of Steam Generator pressure. In this paper, it is concluded that consideration of equipment and setpoint is needed for that Safety Injection has been not occurred under the unnecessary situation. Stable state of nuclear power plant system has been confirmed for Safety Injection and reactor trip event occurred during the ASTS test of hanbit Unit 2. In the result of system safety assessment, major variables of nuclear power plant are located in optimal range and not exceed safety limit. It remains nuclear fuel and the integrity of the plant is in a safe condition were conformed. It is concluded that consideration of equipment and setpoint is needed for that Safety Injection has been not occurred under the unnecessary situation

Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study

Science.gov (United States)

Ahn, Song Vogue; Baik, Soon Koo; Cho, Youn zoo; Koh, Sang Baek; Huh, Ji Hye; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang Young

2016-01-01

Aims The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. Material and Methods The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40–70 years, who participated from 2005–2008 (baseline) without metabolic syndrome and were followed up from 2008–2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. Results During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422–0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124–0.337, Pmetabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

The majority of Danish nontoxic goitre patients are ineligible for Levothyroxine suppressive therapy

DEFF Research Database (Denmark)

Fast, Søren; Bonnema, Steen Joop; Hegedüs, Laszlo

2008-01-01

evaluated clinically including fine needle aspiration biopsy, thyroid scintigraphy and ultrasound. Seven-hundred and forty-five patients (627 women and 118 men; median age 47 years, range 11-90) were potential candidates for LT4-therapy. Based on guidelines we defined conditions where LT4-therapy......OBJECTIVE: Levothyroxine suppressive therapy (LT4-therapy), aimed at shrinking thyroid nodules is controversial. Despite evidence of limited effect and long-term side-effects, questionnaire surveys indicate widespread use. Our aim was to determine, in consecutive nontoxic goitre patients...... serum TSH, post-menopausal status, a large goitre or clinical suspicion of malignancy. CONCLUSION: The vast majority of consecutive Danish nontoxic goitre patients (84%) were ineligible for LT4-therapy. Due to low efficacy and potential long-term adverse effects on the skeleton and cardiovascular system...

Correlation between Aminotransferase Ratio (AST/ALT and Other Biochemical Parameters in Chronic Liver Disease of Viral Origin

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Shah Md Fazlul Karim

2015-03-01

Full Text Available Background: In recent years the ratio of aspartate aminotransferase (AST to alanine aminotransferase (ALT in patients of chronic liver disease (CLD of various origins has gained much attention. This variable is readily available, easy to interpret, and inexpensive and the clinical utility of the AST/ALT ratio in the diagnostic workup of patients with CLD is quite promising. Objective: The present study was designed to find out the link between aminotransferase (AST/ALT ratio with commonly measured biochemical parameters of liver function tests in CLD of viral origin. Materials and method: This cross sectional study was carried out in the department of Biochemistry, Sir Salimullah Medical College, Dhaka, Bangladesh. Forty four biopsy proven diagnosed subjects of chronic viral hepatitis without cirrhosis of both sex were selected purposively. With aseptic precaution 5 mL venous blood was collected from each subject and common liver function tests (serum AST, ALT, AST/ALT ratio, alkaline phosphatase, total bilirubin, serum total protein, serum albumin, serum globulin, serum albumin/globulin ratio, prothrombin time and viral serology (HBsAg, Anti HDV antibody, Anti HCV antibody were performed. Data were analyzed by SPSS version 19 for Windows. Pearson’s correlation test was done to determine association between AST/ALT with other biochemical parameters. Results: Mean(±SD age of the study subjects was 32.55±10.55 years (range 20-50 years with 48 (77.7% male and 14 (22.6% female subjects. Pearson’s correlation test was done between AST to ALT ratio with other biochemical parameters and prothrombin time showed significant positive correlation (p <0.01. Conclusion: In our study we found significant positive correlation between AST/ALT with prothrombin time in CLD subjects without cirrhosis.

Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study

DEFF Research Database (Denmark)

Castillo-Mancilla, Jose R; Phillips, Andrew N; Neaton, James D

2018-01-01

Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMAR...

An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy.

Science.gov (United States)

Dahl, Viktor; Gisslen, Magnus; Hagberg, Lars; Peterson, Julia; Shao, Wei; Spudich, Serena; Price, Richard W; Palmer, Sarah

2014-05-15

We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a nationwide register-based study in Denmark.

Science.gov (United States)

Lødrup, A; Pottegård, A; Hallas, J; Bytzer, P

2015-07-01

Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. To determine the use of proton pump inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients, the Danish National Prescription Register, and the Danish Person Register. The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery to 64.9% 1 year before. The probability for inadequate dosing 1 year before surgery (reflux surgery, as a high proportion of patients receive inadequate dosing of acid-suppressive therapy prior to the operation. © 2015 John Wiley & Sons Ltd.

The thyroid axis 'setpoints' are significantly altered after long-term suppressive LT4 therapy

NARCIS (Netherlands)

Verburg, F.A.; Mader, U.; Grelle, I.; Visser, T.J.; Peeters, R.P.; Smit, J.W.A.; Reiners, C.

2014-01-01

The aim of the study was to investigate the changes in the thyroid axis setpoint after long-term suppressive levothyroxine therapy for differentiated thyroid carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine differentiated thyroid cancer patients were reviewed. All

Translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese.

Science.gov (United States)

Baggio, Gustavo Inheta; Hage, Simone Rocha de Vasconcellos

2017-12-07

To perform the translation and cultural adaptation of the Aguado Syntax Test (AST) into Brazilian Portuguese considering the linguistic and cultural reality of the language. The AST assesses the early morphosyntactic development in children aged 3 to 7 in terms of understanding and expression of various types of structures such as sentences, pronouns, verbal voices, comparisons, prepositions and verbal desinence as to number, mode and tense. The process of translation and cultural adaptation followed four steps: 1) preparation of two translations; 2) synthesis of consensual translations; 3) backtranslation; and 4) verification of equivalence between the initial translations and backtranslations that resulted in the final translated version. The whole process of translation and cultural adaptation revealed the presence of equivalence and reconciliation of the translated items and an almost complete semantic equivalence between the two translations and the absence of consistent translation difficulties. The AST was translated and culturally adapted into Brazilian Portuguese, constituting the first step towards validation and standardization of the test.

Influence of Preoperative Serum Aspartate Aminotransferase (AST Level on the Prognosis of Patients with Non-Small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Shu-Lin Chen

2016-09-01

Full Text Available The purpose of this work is to analyze preoperative serum aspartate aminotransferase (AST levels and their effect on the prognosis of patients with non-small cell lung cancer (NSCLC after surgical operation. These analyses were performed retrospectively in patients with NSCLC followed by surgery; participants were recruited between January 2004 and January 2008. All clinical information and laboratory results were collected from medical records. We explored the association between preoperative serum AST and recurrence-free survival (RFS, and the overall survival (OS of NSCLC patients. Kaplan–Meier analysis and Cox multivariate analysis, stratified by the AST median value, were used to evaluate the prognostic effect. A chi-squared test was performed to compare clinical characteristics in different subgroups. A p-value of ≤0.05 was considered to be statistically significant. A total of 231 patients were enrolled. The median RFS and OS were 22 and 59 months, respectively. The AST levels were divided into two groups, using a cut-off value of 19 U/L: High AST (>19 U/L, n = 113 vs. low AST (≤19 U/L, n = 118. Multivariate analysis indicated that preoperative serum AST > 19 U/L (hazard ratio (HR = 0.685, 95% confidence interval (CI: 0.493–0.994, p = 0.046 for RFS, HR = 0.646, 95% CI: 0.438–0.954, p = 0.028 for OS was an independent prognostic factor for both RFS and OS. High preoperative serum AST levels may serve as a valuable marker to predict the prognosis of NSCLC after operation.

Binocular Therapy for Childhood Amblyopia Improves Vision Without Breaking Interocular Suppression.

Science.gov (United States)

Bossi, Manuela; Tailor, Vijay K; Anderson, Elaine J; Bex, Peter J; Greenwood, John A; Dahlmann-Noor, Annegret; Dakin, Steven C

2017-06-01

Amblyopia is a common developmental visual impairment characterized by a substantial difference in acuity between the two eyes. Current monocular treatments, which promote use of the affected eye by occluding or blurring the fellow eye, improve acuity, but are hindered by poor compliance. Recently developed binocular treatments can produce rapid gains in visual function, thought to be as a result of reduced interocular suppression. We set out to develop an effective home-based binocular treatment system for amblyopia that would engage high levels of compliance but that would also allow us to assess the role of suppression in children's response to binocular treatment. Balanced binocular viewing therapy (BBV) involves daily viewing of dichoptic movies (with "visibility" matched across the two eyes) and gameplay (to monitor compliance and suppression). Twenty-two children (3-11 years) with anisometropic (n = 7; group 1) and strabismic or combined mechanism amblyopia (group 2; n = 6 and 9, respectively) completed the study. Groups 1 and 2 were treated for a maximum of 8 or 24 weeks, respectively. The treatment elicited high levels of compliance (on average, 89.4% ± 24.2% of daily dose in 68.23% ± 12.2% of days on treatment) and led to a mean improvement in acuity of 0.27 logMAR (SD 0.22) for the amblyopic eye. Importantly, acuity gains were not correlated with a reduction in suppression. BBV is a binocular treatment for amblyopia that can be self-administered at home (with remote monitoring), producing rapid and substantial benefits that cannot be solely mediated by a reduction in interocular suppression.

Gastric ulcer treatment: cure of Helicobacter pylori infection without subsequent acid-suppressive therapy: is it effective?

Science.gov (United States)

van Zanten, Sander Veldhuyzen; van der Knoop, Bloeme

2008-06-01

Whether it is a requirement to continue with anti-secretory therapy following anti-Helicobacter therapy in H. pylori positive gastric ulcers is an important question. As gastric ulcers tend to heal more slowly than duodenal ulcers, may be asymptomatic or only causing mild symptoms and success at curing H. pylori with current fist line therapies is 80% at best, clinicians will likely err on the side of caution and continue acid suppressive therapy to ensure healing of gastric ulcers. This is certainly recommended when dealing with bleeding ulcers.

X-ray electron spectra of chalcogenide glasses and polycrystalline alloys of Ge-Te and As-Te systems

International Nuclear Information System (INIS)

Panus, V.R.

1990-01-01

Comparative investigation into structures of crystals and glasses in Ge-Te and As-Te two-component systems was conducted. Analysis of x-ray electron spectra of Ge-Te and As-Te systems indicates, that processes of dissociation-association resulting in formation of new structure units occur in telluride melts at synthesis temperatures. Structural chemical composition of binary glass-like alloys of Ge-Te and As-Te systems differs essentially from the one that corresponds to fusibility equilibrium curve. Oxygen doping into tellurium-base glasses results mainly in occurence of structures forecasted due to thermochemical calculation

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

Science.gov (United States)

Kilduff, Claire E; Counter, Melanie J; Thomas, Gareth A; Harrison, Nicholas K; Hope-Gill, Benjamin D

2014-01-01

Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use

The effects of thyrotropin-suppressive therapy on bone metabolism in patients with well-differentiated thyroid carcinoma

NARCIS (Netherlands)

Heemstra, K. A.; Hamdy, N. A. T.; Romijn, J. A.; Smit, J. W. A.

2006-01-01

Patients with differentiated thyroid carcinoma (DTC) are commonly treated long-term with thyrotropin (TSH)- suppressive thyroxine replacement therapy resolving in a state of subclinical hyperthyroidism. The relationship between subclinical hyperthyroidism and osteoporosis is not clear. In this

Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam

Science.gov (United States)

Jordan, Michael R; La, Hanh; Nguyen, Hien Duc; Sheehan, Heidi; Lien, Trinh Thi Minh; Van Dang, Duong; Hellinger, James; Wanke, Christine; Tang, Alice M

2009-01-01

Summary Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programs. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy (ART) for at least 6 months in Hanoi, Vietnam. Mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA 95% adherence (p<0.01) and current use of trimethoprim/sulfamethoxazole (p<0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (p=0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlights the need for adherence promotion, risk reduction programs, and population based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. PMID:19451329

Non-amidated and amidated members of the C-type allatostatin (AST-C) family are differentially distributed in the stomatogastric nervous system of the American lobster, Homarus americanus.

Science.gov (United States)

Christie, Andrew E; Miller, Alexandra; Fernandez, Rebecca; Dickinson, Evyn S; Jordan, Audrey; Kohn, Jessica; Youn, Mina C; Dickinson, Patsy S

2018-01-13

The crustacean stomatogastric nervous system (STNS) is a well-known model for investigating neuropeptidergic control of rhythmic behavior. Among the peptides known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster, Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies were generated against one of the non-amidated peptides (AST-C I) and against the amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II antibody does not cross-react with either non-amidated peptide. Wholemount immunohistochemistry shows that both subclasses (non-amidated and amidated) of AST-C are distributed throughout the lobster STNS. Specifically, the antibody that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG). The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG, and two somata in the STG. Double immunolabeling shows that, except for one soma in each CoG, the non-amidated and amidated peptides are present in distinct sets of neuronal profiles. The differential distributions of the two AST-C subclasses suggest that the two peptide groups are likely to serve different modulatory roles in the lobster STNS.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

Science.gov (United States)

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-06-01

The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

Suppressive therapy for radiation-associated nodular thyroid disease

International Nuclear Information System (INIS)

Tamura, Kazuo; Shimaoka, Katsutaro; Tsukada, Yoshiaki; Razack, M.S.; Sciasicia, Michael.

1981-01-01

A thyroid screening program for individuals who had irradiation to the head and neck areas was started at Roswell Park Memorial Institute in February 1977 and by June 1979, 1,071 patients were seen in the clinic. Three hundred and ninety-six patients were found to have palpable abnormalities of the thyroid, and following pretreatment evaluation, suppressive therapy with triiodothyronine (T3) (50 μg/day) or DT (desiccated thyroid) (120 mg/day) was administered in a double-blind fashion. Two hundred fifty patients with nodular disease completed 6 mo of treatment and are analyzed in this paper. Pretreatment thyroid function tests showed that two patients had hypothyroidism with a high thyroid-stimulating hormone (TSH) and a low thyroxine level. A high incidence of thyroid autoantibodies was also noted and surgical findings confirmed a high incidence of chronic thyroiditis. Complete disappearance of the nodules was seen in 29% of the patients, and in addition, 38% of the patients were seen to have significant shrinkage of the nodules, indicating that radiation-associated thyroid nodules were as sensitive to the thyroactive agents as nonirradiated nodular thyroid disease. There was little difference in the response rate between T3 and DT. Both agents suppressed circulating TSH levels to an unmeasurable level in 76% of the patients. There was no correlation between scan findings and response rates. Thyroid carcinoma was found in 19% of the patients who underwent surgery; although all were well-differentiated carcinomas, two-thirds of the patients already had evidence of dissemination and/or invasion suggesting the aggressive nature of postirradiation thyroid carcinoma. (author)

Kas Gaddafi tõesti põgenes Liibüast? / Heiki Suurkask

Index Scriptorium Estoniae

Suurkask, Heiki, 1972-

2011-01-01

Suur autokolonn Liibüa diktaatori Muammar Gaddafi lähikondlaste ja varandusega jõudis Liibüast Nigeri kaudu Burkina Fasosse. USA võimude andmeil Gaddafit kolonnis ei viibi. Burkina Faso valitsus väidab, et nad ei paku Gaddafile varjupaika. Kaart: Gaddafi võimalik põgenemistee

Nonlinear system identification for prostate cancer and optimality of intermittent androgen suppression therapy.

Science.gov (United States)

Suzuki, Taiji; Aihara, Kazuyuki

2013-09-01

These days prostate cancer is one of the most common types of malignant neoplasm in men. Androgen ablation therapy (hormone therapy) has been shown to be effective for advanced prostate cancer. However, continuous hormone therapy often causes recurrence. This results from the progression of androgen-dependent cancer cells to androgen-independent cancer cells during the continuous hormone therapy. One possible method to prevent the progression to the androgen-independent state is intermittent androgen suppression (IAS) therapy, which ceases dosing intermittently. In this paper, we propose two methods to estimate the dynamics of prostate cancer, and investigate the IAS therapy from the viewpoint of optimality. The two methods that we propose for dynamics estimation are a variational Bayesian method for a piecewise affine (PWA) system and a Gaussian process regression method. We apply the proposed methods to real clinical data and compare their predictive performances. Then, using the estimated dynamics of prostate cancer, we observe how prostate cancer behaves for various dosing schedules. It can be seen that the conventional IAS therapy is a way of imposing high cost for dosing while keeping the prostate cancer in a safe state. We would like to dedicate this paper to the memory of Professor Luigi M. Ricciardi. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive antiretroviral therapy in Western India.

Science.gov (United States)

Dravid, Ameet N; Natrajan, Kartik; Kulkarni, Milind M; Saraf, Chinmay K; Mahajan, Uma S; Kore, Sachin D; Rathod, Niranjan M; Mahajan, Umakant S; Wadia, Rustom S

2018-02-01

Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA (complete viral suppression, VL ≤20 copies/mL) or CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low-level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%) presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in patients with discordance was 120 [interquartile range (IQR): CSF HIV-1 genotypic resistance testing was done showed mutations that would compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA discordance was higher among neurologically symptomatic patients with plasma LLV as compared with those with complete viral suppression (70% vs 11.8%, P CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has adapted to the CNS or has developed antiretroviral drug resistance. Larger studies should be performed to study incidence of discordance in India. This will help in managing patients presenting with neurologic symptoms on suppressive ART with appropriate neuroeffective therapy.

Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

Science.gov (United States)

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-01-01

Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

Quantum-field theories as representations of a single $^\\ast$-algebra

OpenAIRE

Raab, Andreas

2013-01-01

We show that many well-known quantum field theories emerge as representations of a single $^\\ast$-algebra. These include free quantum field theories in flat and curved space-times, lattice quantum field theories, Wightman quantum field theories, and string theories. We prove that such theories can be approximated on lattices, and we give a rigorous definition of the continuum limit of lattice quantum field theories.

LHCb: Measurement of the polarization amplitudes of the decay $B^0 \\rightarrow J/\\psi K^\\ast$

CERN Multimedia

Linn, C

2011-01-01

Using the data sample recorded with the LHCb detector in 2010 we perform a combined angular and lifetime analysis of the decay $B^0 \\rightarrow J/\\psi K^\\ast$. The data corresponds to an integrated luminosity of about 36 pb$^{-1}$ and was taken at the LHC at an centre-of-mass energy of $\\sqrt{s}$= 7 TeV. A total of 3909 $J/\\psi K^*$ candidates are found and are used to extract the polarisation amplitudes and the corresponding strong phases for the decays $B_d \\rightarrow J/\\psi K^\\ast$.

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

DEFF Research Database (Denmark)

Reekie, J; Mocroft, A; Ledergerber, B

2010-01-01

OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategi...

Peak Serum AST Is a Better Predictor of Acute Liver Graft Injury after Liver Transplantation When Adjusted for Donor/Recipient BSA Size Mismatch (ASTi

Directory of Open Access Journals (Sweden)

Kyota Fukazawa

2014-01-01

Full Text Available Background. Despite the marked advances in the perioperative management of the liver transplant recipient, an assessment of clinically significant graft injury following preservation and reperfusion remains difficult. In this study, we hypothesized that size-adjusted AST could better approximate real AST values and consequently provide a better reflection of the extent of graft damage, with better sensitivity and specificity than current criteria. Methods. We reviewed data on 930 orthotopic liver transplant recipients. Size-adjusted AST (ASTi was calculated by dividing peak AST by our previously reported index for donor-recipient size mismatch, the BSAi. The predictive value of ASTi of primary nonfunction (PNF and graft survival was assessed by receiver operating characteristic curve, logistic regression, Kaplan-Meier survival, and Cox proportional hazard model. Results. Size-adjusted peak AST (ASTi was significantly associated with subsequent occurrence of PNF and graft failure. In our study cohort, the prediction of PNF by the combination of ASTi and PT-INR had a higher sensitivity and specificity compared to current UNOS criteria. Conclusions. We conclude that size-adjusted AST (ASTi is a simple, reproducible, and sensitive marker of clinically significant graft damage.

Higher Anti-CMV IgG Concentrations are Associated with Worse Neurocognitive Performance During Suppressive Antiretroviral Therapy.

Science.gov (United States)

Letendre, Scott; Bharti, Ajay; Perez-Valero, Ignacio; Hanson, Barbara; Franklin, Donald; Woods, Steven Paul; Gianella, Sara; de Oliveira, Michelli Faria; Heaton, Robert K; Grant, Igor; Landay, Alan L; Lurain, Nell

2018-03-01

To determine the association of CMV infection with neurocognitive performance in HIV+ adults. Cross-sectional, observational, exploratory study. Anti-CMV IgG concentrations in blood and CMV DNA copies in blood and cerebrospinal fluid (CSF) were measured in stored specimens of 80 HIV+ adults who were previously assessed with a standardized, comprehensive neurocognitive test battery. Thirty-eight were taking suppressive antiretroviral therapy (ART, HIV RNA ≤ 50 copies/mL) and 42 were not taking ART. A panel of 7 soluble biomarkers were also measured by immunoassay in CSF. Anti-CMV IgG concentrations ranged from 5.2 to 46.1 U/mL. CMV DNA was detected in 7 (8.8%) blood plasma but in none of the CSF specimens. Higher anti-CMV IgG levels were associated with older age (p=0.0017), lower nadir CD4+ T-cell count (pperformance overall (p=0.059). This correlation was present in those taking suppressive ART (p=0.0049) but not in those who were not taking ART (p=0.92). Worse neurocognitive performance remained associated with higher anti-CMV IgG levels after accounting for other covariates in multivariate models (Model p=0.0038). Detectable plasma CMV DNA was associated with AIDS (p=0.05) but not with neurocognitive performance. CMV may influence neurocognitive performance in HIV+ adults taking suppressive ART. Future clinical trials of anti-CMV therapy should help determine whether the observed relationships are causal.

Measurement of $H{\\to}W^\\pm W^{\\mp\\ast}{\\to}\\ell^-\\bar{\

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00423318; Köneke, Karsten

This thesis presents and discusses measurements of the coupling of the Higgs boson to vector bosons, using data collected at $\\sqrt{s}=13$ TeV by the ATLAS detector. A full analysis of the first $5.8$ fb${}^{-1}$ of LHC Run 2 data investigating the $H{\\to}W^\\pm W^{\\mp\\ast}{\\to}\\ell^-\\bar{\

Impact of targeted educational interventions on appropriateness of stress ulcer prophylaxis in critically ill adults.

Science.gov (United States)

Hammond, Drayton A; Killingsworth, Catherine A; Painter, Jacob T; Pennick, Rose E; Chatterjee, Kshitij; Boye, Bradley; Meena, Nikhil

2017-01-01

Acid suppression therapy (AST) is routinely used in critically ill patients to prevent stress-related mucosal bleeding (SRMB). Our objective was to determine the impact of a structured educational intervention on AST used for prevention of SRMB on appropriateness of AST. A single-center, retrospective, cohort study of appropriate use of AST in critically ill patients admitted to the medical intensive care unit (ICU) at an academic medical center between January to June of 2014 (no intervention) and January to June of 2015 (intervention) was conducted. The percentage of patients prescribed inappropriate AST, inappropriate AST at ICU transfer and hospital discharge, doses of inappropriate AST, and adverse effects associated with AST use were compared between periods using chi-square tests. Patients in the intervention group (n=118) were 5 years older than patients in the no intervention group (n=101). AST was inappropriately initiated more frequently in the no intervention group (23% vs. 11%, p=0.012). Continuation of inappropriate AST at ICU transfer and hospital discharge was similar between groups (60% vs. 53%, p=0.277 and 18% vs. 14%, p=0.368, respectively). Patients had appropriate AST initiated and inappropriate AST withheld more frequently when formal education was provided. This low-cost intervention strategy can be implemented easily at institutions where pharmacists interact with physicians on rounding services and should be evaluated in institutions where interactions between pharmacists and physicians occur more frequently in non-rounding situations.

Impact of targeted educational interventions on appropriateness of stress ulcer prophylaxis in critically ill adults

Directory of Open Access Journals (Sweden)

Hammond DA

2017-09-01

Full Text Available Background: Acid suppression therapy (AST is routinely used in critically ill patients to prevent stress-related mucosal bleeding (SRMB. Objective: Our objective was to determine the impact of a structured educational intervention on AST used for prevention of SRMB on appropriateness of AST. Methods: A single-center, retrospective, cohort study of appropriate use of AST in critically ill patients admitted to the medical intensive care unit (ICU at an academic medical center between January to June of 2014 (no intervention and January to June of 2015 (intervention was conducted. The percentage of patients prescribed inappropriate AST, inappropriate AST at ICU transfer and hospital discharge, doses of inappropriate AST, and adverse effects associated with AST use were compared between periods using chi-square tests. Results: Patients in the intervention group (n=118 were 5 years older than patients in the no intervention group (n=101. AST was inappropriately initiated more frequently in the no intervention group (23% vs. 11%, p=0.012. Continuation of inappropriate AST at ICU transfer and hospital discharge was similar between groups (60% vs. 53%, p=0.277 and 18% vs. 14%, p=0.368, respectively. Conclusion: Patients had appropriate AST initiated and inappropriate AST withheld more frequently when formal education was provided. This low-cost intervention strategy can be implemented easily at institutions where pharmacists interact with physicians on rounding services and should be evaluated in institutions where interactions between pharmacists and physicians occur more frequently in non-rounding situations.

Coupling of AST-500 heating reactors with desalination facilities

International Nuclear Information System (INIS)

Kourachenkov, A.V.

1998-01-01

The general issues regarding NHR and desalination facility joint operation for potable water production are briefly considered. AST-500 reactor plant and DOU GTPA-type evaporating desalination facilities, both relying on proven technology and solid experience of construction and operation, are taken as a basis for the design of a large-output nuclear desalination complex. Its main design characteristics are given. Similarity of NHR operation for a heating grid and a desalination facility in respect of reactor plant operating conditions and power regulation principles is pointed out. The issues of nuclear desalination complexes composition are discussed briefly as well. (author)

Cold suppresses agonist-induced activation of TRPV1.

Science.gov (United States)

Chung, M-K; Wang, S

2011-09-01

Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

[Suppression of tinnitus by band noise masker--a study of 600 cases].

Science.gov (United States)

Watanabe, K; Kamio, T; Ohkawara, D; Aoki, H; Baba, S; Yagi, T

1997-09-01

We performed Band Noise Masker (BNM) therapy for the suppression of tinnitus in 600 patients and measured the pitch, loudness and masking level of tinnitus and residual inhibition (RI). We examined the efficiency of BNM therapy. The purpose of this study was to investigate the mechanism of suppression of tinnitus by BNM. Tinnitus was suppressed in 394 patients (66%) after BNM therapy. In the group of patients in whom we suppressed tinnitus, the loudness of tinnitus was reduced from 7.7 +/- 5.7dBSL to 7.5 +/- 5.5dBSL (p pitch of tinnitus did not exhibit a marked change. In the group of patients in whom we did not suppress tinnitus, the loudness and pitch of tinnitus did not exhibit a marked change. The efficiency of BNM therapy was high in the cases of presbyacusis and low in the cases of sudden deafness. There was no significant relationship between RI and the efficiency of BNM therapy. We examined these data and discussed the mechanism of suppression of tinnitus by BNM therapy. In all cases, after BNM therapy, the auditory threshold did not become worse. In 4 cases tinnitus became worse temporarily. In conclusion, BNM therapy is an effective mode for tinnitus control, is easily performed in our outpatient clinic or at home, and has no serious complications.

Coupling of AST-500 heating reactors with desalination facilities

International Nuclear Information System (INIS)

Gureyeva, L.V.; Egorov, V.V.; Podberezniy, V.L.

1997-01-01

The general issues regarding the joint operation of a NHR and a desalination facility for potable water production are briefly considered. The AST-500 reactor plant and the DOUGTPA-type evaporating desalination facilities, both relying on proven technology and solid experience of construction and operation, are taken as a basis for the design of a large-output nuclear desalination complex. Its main design characteristics are given. The similarity of NHR operation for heating grid and desalination facility in respect of reactor plant operating conditions and power regulation principles is pointed out. The issues of nuclear desalination complexes composition are discussed briefly as well. (author). 2 refs, 1 fig., 1 tab

Coupling of AST-500 heating reactors with desalination facilities

Energy Technology Data Exchange (ETDEWEB)

Gureyeva, L V; Egorov, V V [OKBM, Nizhny Novgorod (Russian Federation); Podberezniy, V L [Scientific Research Inst. of Machine Building, Ekaterinburg (Russian Federation)

1997-09-01

The general issues regarding the joint operation of a NHR and a desalination facility for potable water production are briefly considered. The AST-500 reactor plant and the DOUGTPA-type evaporating desalination facilities, both relying on proven technology and solid experience of construction and operation, are taken as a basis for the design of a large-output nuclear desalination complex. Its main design characteristics are given. The similarity of NHR operation for heating grid and desalination facility in respect of reactor plant operating conditions and power regulation principles is pointed out. The issues of nuclear desalination complexes composition are discussed briefly as well. (author). 2 refs, 1 fig., 1 tab.

Astakine LvAST binds to the β subunit of F1-ATP synthase and likely plays a role in white shrimp Litopeneaus vannamei defense against white spot syndrome virus.

Science.gov (United States)

Liang, Gao-Feng; Liang, Yan; Xue, Qinggang; Lu, Jin-Feng; Cheng, Jun-Jun; Huang, Jie

2015-03-01

Cytokines play a critical role in innate and adaptive immunity. Astakines represent a group of invertebrate cytokines that are related to vertebrate prokineticin and function in promoting hematopoiesis in crustaceans. We have identified an astakine from the white shrimp Litopeneaus vannamei and named it LvAST in a previous research. In the present research, we investigated the interactions among LvAST, the envelope protein VP37 of white spot syndrome virus (i.e., WSSV), and the β subunit of F1-ATP synthase (ATPsyn-β) of the white shrimp (i.e., BP53) using binding assays and co-precipitations. We also examined the effects of LvAST on shrimp susceptibility to WSSV. We found that LvAST and VP37 competitively bound to BP53, but did not bind to each other. Shrimps that had been injected with recombinant LvAST exhibited significantly lower mortality and longer survival time in experimental infections by WSSV. In contrast, shrimps whose LvAST gene expression had been inhibited by RNA interference showed significantly higher WSSV infection intensity and shorter survival time following viral challenges. These results suggested that LvAST and WSSV both likely use ATPsyn-β as a receptor and LvAST plays a role in shrimp defense against WSSV infection. This represented the first research showing the involvement of astakines in host antiviral immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis.

Science.gov (United States)

Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana

2016-01-01

hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion.

Acid suppression therapy does not predispose to Clostridium difficile infection: the case of the potential bias.

Directory of Open Access Journals (Sweden)

Lena Novack

Full Text Available OBJECTIVE: An adverse effect of acid-suppression medications on the occurrence of Clostridium difficile infection (CDI has been a common finding of many, but not all studies. We hypothesized that association between acid-suppression medications and CDI is due to the residual confounding in comparison between patients with infection to those without, predominantly from non-tested and less sick subjects. We aimed to evaluate the effect of acid suppression therapy on incidence of CDI by comparing patients with CDI to two control groups: not tested patients and patients suspected of having CDI, but with a negative test. METHODS: We conducted a case-control study of adult patients hospitalized in internal medicine department of tertiary teaching hospital between 2005-2010 for at least three days. Controls from each of two groups (negative for CDI and non-tested were individually matched (1:1 to cases by primary diagnosis, Charlson comorbidity index, year of hospitalization and gender. Primary outcomes were diagnoses of International Classification of Diseases (ICD-9-coded CDI occurring 72 hours or more after admission. RESULTS: Patients with CDI were similar to controls with a negative test, while controls without CDI testing had lower clinical severity. In multivariable analysis, treatment by acid suppression medications was associated with CDI compared to those who were not tested (OR = 1.88, p-value = 0.032. Conversely, use of acid suppression medications in those who tested negative for the infection was not associated with CDI risk as compared to the cases (OR = 0.66; p = 0.059. CONCLUSIONS: These findings suggest that the reported epidemiologic associations between use of acid suppression medications and CDI risk may be spurious. The control group choice has an important impact on the results. Clinical differences between the patients with CDI and those not tested and not suspected of having the infection may explain the different conclusions

Thyrotropin Suppressive Therapy for Low-Risk Small Thyroid Cancer: A Propensity Score-Matched Cohort Study.

Science.gov (United States)

Park, Suyeon; Kim, Won Gu; Han, Minkyu; Jeon, Min Ji; Kwon, Hyemi; Kim, Mijin; Sung, Tae-Yon; Kim, Tae Yong; Kim, Won Bae; Hong, Suck Joon; Shong, Young Kee

2017-09-01

Thyrotropin (TSH) suppression has improved the clinical outcomes of patients with differentiated thyroid cancer (DTC). However, the efficacy of TSH suppressive therapy (TST) is unclear in patients with low-risk DTC. This study aimed to evaluate the efficacy of TST and optimal TSH levels of patients with low-risk DTC. This retrospective propensity score-matched cohort study included DTC patients (n = 446) who underwent lobectomy from 2002 to 2008 with or without TST (TST group and No-TST group). Disease-free survival (DFS) and dynamic risk stratification were compared between both groups using serum TSH levels. Approximately 74% of TST patients and 11% of No-TST patients had suppressed serum TSH levels (<2 mIU/L). The median follow-up period was 8.6 years. During follow-up, the disease recurred in 10 (2.7%) patients, with no significant difference in DFS between the groups (p = 0.63). The proportion of patients with excellent treatment response was similar between the TST (65.2%) and No-TST (64.4%) groups. Incomplete biochemical response was noted in 17.2% of the TST group patients and 9.4% of the No-TST group patients. No significant difference was observed in the DFS between both groups by comparing serum TSH level (p = 0.57). TST did not improve clinical outcomes, and serum TSH levels were not associated with recurrence in patients with low-risk small DTC. No clinical benefits were shown for TSH suppression in low-risk patients who underwent lobectomy. Thus, levothyroxine is not necessary for patients without evidence of hypothyroidism.

AST: an automated sequence-sampling method for improving the taxonomic diversity of gene phylogenetic trees.

Science.gov (United States)

Zhou, Chan; Mao, Fenglou; Yin, Yanbin; Huang, Jinling; Gogarten, Johann Peter; Xu, Ying

2014-01-01

A challenge in phylogenetic inference of gene trees is how to properly sample a large pool of homologous sequences to derive a good representative subset of sequences. Such a need arises in various applications, e.g. when (1) accuracy-oriented phylogenetic reconstruction methods may not be able to deal with a large pool of sequences due to their high demand in computing resources; (2) applications analyzing a collection of gene trees may prefer to use trees with fewer operational taxonomic units (OTUs), for instance for the detection of horizontal gene transfer events by identifying phylogenetic conflicts; and (3) the pool of available sequences is biased towards extensively studied species. In the past, the creation of subsamples often relied on manual selection. Here we present an Automated sequence-Sampling method for improving the Taxonomic diversity of gene phylogenetic trees, AST, to obtain representative sequences that maximize the taxonomic diversity of the sampled sequences. To demonstrate the effectiveness of AST, we have tested it to solve four problems, namely, inference of the evolutionary histories of the small ribosomal subunit protein S5 of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a study of ancient horizontal gene transfers from bacteria to plants. Our results show that the resolution of our computational results is almost as good as that of manual inference by domain experts, hence making the tool generally useful to phylogenetic studies by non-phylogeny specialists. The program is available at http://csbl.bmb.uga.edu/~zhouchan/AST.php.

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

LENUS (Irish Health Repository)

Abdel Aziz, Mohamed T

2011-05-05

Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

C/EBPα Short-Activating RNA Suppresses Metastasis of Hepatocellular Carcinoma through Inhibiting EGFR/β-Catenin Signaling Mediated EMT.

Directory of Open Access Journals (Sweden)

Hongbo Huan

Full Text Available Hepatocellular carcinoma is associated with high mortality, and tumor metastasis is an important reason for poor prognosis. However, metastasis has not been effectively prevented in clinical therapy and the mechanisms underlying metastasis have not been fully characterized. CCAAT/enhancer-binding protein-α (C/EBPα is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA to enhance expression of C/EBPα. Intravenous injection of C/EBPα-saRNA in a nude mouse liver orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis. C/EBPα-saRNA-treated mice showed increased serum levels of albumin and decreased alanine aminotransferase (ALT, glutamic-oxalacetic transaminase (AST, indicating a role of C/EBPα in improving liver function. Migration and invasion were inhibited in hepatoma cell lines transfected with C/EBPα-saRNA. We also observed an inhibition of epithelial-mesenchymal transition (EMT and suppression of epidermal growth factor receptor (EGFR, EGFR phosphorylation, and β-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that C/EBPα-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/β-catenin signaling pathway mediated EMT in vitro and in vivo.

Arctigenin protects against liver injury from acute hepatitis by suppressing immune cells in mice.

Science.gov (United States)

Cheng, Xixi; Wang, Huafeng; Yang, Jinlai; Cheng, Yingnan; Wang, Dan; Yang, Fengrui; Li, Yan; Zhou, Dongmei; Wang, Yanxia; Xue, Zhenyi; Zhang, Lijuan; Zhang, Qi; Yang, Luhong; Zhang, Rongxin; Da, Yurong

2018-06-01

As a phenylpropanoid and dibenzylbutyrolactone lignan present in medical plants, such as those used in traditional Chinese herbal medicine, including Arctium lappa (Niubang), arctigenin exhibits antimicrobial, anti-inflammatory, and anticancer activities. In this study, we investigated the protective role of arctigenin in Concanavalin A (ConA)-induced acute hepatitis in mice. Arctigenin remarkably reduced the congestion and necroinflammation of livers, and improved hepatic function (ALT and AST) in ConA-induced acute hepatitis in vivo. The infiltration of CD4 T, NKT and macrophages into the livers was found to be reduced with arctigenin treatment. Arctigenin suppressed ConA-induced T lymphocyte proliferations that might have resulted from enhanced IL-10 production by macrophages and CD4 T cells. These results suggested that arctigenin could be a powerful drug candidate for acute hepatitis through immune suppression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

International Nuclear Information System (INIS)

Fahmueller, Yvonne Nadine; Nagel, Dorothea; Hoffmann, Ralf-Thorsten; Tatsch, Klaus; Jakobs, Tobias; Stieber, Petra; Holdenrieder, Stefan

2012-01-01

Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy

Suppression of experimental tractional retinal detachment by low-dose radiation therapy

International Nuclear Information System (INIS)

Meredith, T.A.; Ficker, L.; Stevens, R.; Olkowski, Z.; Anderson, M.; Hartmann, J.; Crocker, I.

1988-01-01

We used a standardized model of traction retinal detachment (TRD) created by cellular membranes in the rabbit to test the effects of low-dose radiation therapy in suppressing TRD. The vitreous and lens were removed from pigmented rabbits, and homologous conjunctival fibroblasts were grown in cell culture. After resolution of postoperative inflammation, 50,000 fibroblasts in 0.1 mL of culture fluid were injected into the vitreous cavity. Ten eyes were maintained as controls. Nineteen eyes received 6 Gy (600 rad) of x-ray irradiation one to three hours after cellular injection. Eyes were monitored weekly for three weeks with indirect ophthalmoscopy. Seven (70%) of ten control eyes developed TRD at one week; no additional TRDs were noted at weeks 2 and 3. Significantly smaller numbers of irradiated eyes developed TRD: at week 1, two (11%) of 19; at week 2, five (28%) of 18; and at week 3, five (29%) of 17

Impact of Active Drug Use on Antiretroviral Therapy Adherence and Viral Suppression in HIV-infected Drug Users

OpenAIRE

Arnsten, Julia H; Demas, Penelope A; Grant, Richard W; Gourevitch, Marc N; Farzadegan, Homayoon; Howard, Andrea A; Schoenbaum, Ellie E

2002-01-01

Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening po...

Measurement prospects for VBF $H{\\rightarrow\\,}WW^{(\\ast)}{\\rightarrow\\,}e\

CERN Document Server

The ATLAS collaboration

2016-01-01

This note presents the prospects for the ATLAS experiment to observe and measure Vector Boson Fusion (VBF) Higgs-boson production, with the Higgs boson decaying into two $W$ bosons in the High Luminosity LHC environment. The production of two forward jets in association with the Higgs boson, as well as the requirement that the $W$ bosons both decay to leptons, provides a distinctive detector signature. The VBF production process has the second largest Higgs-boson production cross-section at the LHC and can be computed with small theoretical uncertainties. These properties allow for precision measurements in the High Luminosity LHC with 3 $\\textrm{ab}^{-1}$ of data. In addition, measurements of the VBF $H{\\rightarrow\\,}WW^{(\\ast)}{\\rightarrow\\,}e\

Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis.

Science.gov (United States)

Petersen, Maya L; Wang, Yue; van der Laan, Mark J; Guzman, David; Riley, Elise; Bangsberg, David R

2007-10-01

Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. Data were obtained from an observational cohort of 245 human immunodeficiency virus (HIV)-infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. Pillbox organizer use was estimated to improve adherence by 4.1%-4.5% and was associated with a decrease in viral load of 0.34-0.37 log10 copies/mL and a 14.2%-15.7% higher probability of achieving a viral load organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of approximately $19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.

Variable Stars Observed in the Galactic Disk by AST3-1 from Dome A, Antarctica

Energy Technology Data Exchange (ETDEWEB)

Wang, Lingzhi; Ma, Bin; Hu, Yi; Liu, Qiang; Shang, Zhaohui [Key Laboratory of Optical Astronomy, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Li, Gang; Fu, Jianning [Department of Astronomy, Beijing Normal University, Beijing, 100875 (China); Wang, Lifan; Cui, Xiangqun; Du, Fujia; Gong, Xuefei; Li, Xiaoyan; Li, Zhengyang; Yuan, Xiangyan; Zhou, Jilin [Chinese Center for Antarctic Astronomy, Nanjing 210008 (China); Ashley, Michael C. B. [School of Physics, University of New South Wales, NSW 2052 (Australia); Pennypacker, Carl R. [Center for Astrophysics, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); York, Donald G., E-mail: wanglingzhi@bao.ac.cn [Department of Astronomy and Astrophysics and Enrico Fermi Institute, University of Chicago, Chicago, IL 60637 (United States)

2017-03-01

AST3-1 is the second-generation wide-field optical photometric telescope dedicated to time-domain astronomy at Dome A, Antarctica. Here, we present the results of an i -band images survey from AST3-1 toward one Galactic disk field. Based on time-series photometry of 92,583 stars, 560 variable stars were detected with i magnitude ≤16.5 mag during eight days of observations; 339 of these are previously unknown variables. We tentatively classify the 560 variables as 285 eclipsing binaries (EW, EB, and EA), 27 pulsating variable stars ( δ Scuti, γ Doradus, δ Cephei variable, and RR Lyrae stars), and 248 other types of variables (unclassified periodic, multiperiodic, and aperiodic variable stars). Of the eclipsing binaries, 34 show O’Connell effects. One of the aperiodic variables shows a plateau light curve and another variable shows a secondary maximum after peak brightness. We also detected a complex binary system with an RS CVn-like light-curve morphology; this object is being followed-up spectroscopically using the Gemini South telescope.

[The advances of suppression in research of amblyopia].

Science.gov (United States)

Liu, S; Liu, H

2016-04-11

Suppression that is the result of interocular competition is an important machanism of amblyopia. The imbalance of suppression may lead the consequence to amblyopia. In the early study, researchers had raised the theory of II. Quadratic Summation which had revealed the relationship of interocular interaction and suppression. In some basic researches, other studies had showed the most possible anatomic location of suppression. Recently, researchers found a new method to quantify the interocular suppression named the noise model. Further studies found a novel disinhibition therapy to treat amblyopia. We summarized the research advances in suppression and disinhibition treatment in amblyopia. (Chin J Ophthalmol, 2016, 52: 305-308).

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy

DEFF Research Database (Denmark)

Rodger, Alison J; Cambiano, Valentina; Bruun, Tina

2016-01-01

IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the ra...

LIPID PEROXIDATION AND BIOCHEMICAL PROFILE IN PRE AND POST ELECTROCONVULSIVE THERAPY IN PSYCHIATRIC PATIENTS

OpenAIRE

Narasimha Rao Babji; Santhisree

2014-01-01

OBJECTIVE: Electroconvulsive therapy (ECT) is an important treatment for a variety of neuropsychiatric disorders. The invasiveness of the procedure and major adverse effects of memory loss and confusion are limiting variables in the use of ECT. Free radical molecules are released during a shock seizure. The effect of electroconvulsive therapy on lipid peroxidation and on enzymes is not well studied. In the present study Malondialdehyde (MDA), Aspartate transaminase (AST), Alan...

Antigen spot test (AST): a highly sensitive assay for the detection of antibodies

Energy Technology Data Exchange (ETDEWEB)

Herbrink, P; van Bussel, F J; Warnaar, S O [Rijksuniversiteit Leiden (Netherlands)

1982-02-12

A method is described for detection of antibodies by means of nitrocellulose or diazobenzyloxymethyl (DBM) paper on which various antigens have been spotted. The sensitivity of this antigen spot test (AST) is comparable with that of RIA and ELISA. The method requires only nanogram amounts of antigen. Since a variety of antigens can be spotted on a single piece of nitrocellulose or DBM paper, this antigen spot test is especially useful for specificity controls on antibodies.

Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study

OpenAIRE

Cerutti, Bernard; Broers, Barbara; Masetsibi, Motlomelo; Faturiyele, Olatunbosun; Toti-Mokoteli, Likabelo; Motlatsi, Mokete; Bader, Joelle; Klimkait, Thomas; Labhardt, Niklaus D

2016-01-01

Abstract Background Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. Methods This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Results Among 1,388 adult p...

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy

NARCIS (Netherlands)

Rodger, Alison J.; Cambiano, Valentina; Bruun, Tina; Vernazza, Pietro; Collins, Simon; van Lunzen, Jan; Corbelli, Giulio Maria; Estrada, Vicente; Geretti, Anna Maria; Beloukas, Apostolos; Asboe, David; Viciana, Pompeyo; Gutiérrez, Félix; Clotet, Bonaventura; Pradier, Christian; Gerstoft, Jan; Weber, Rainer; Westling, Katarina; Wandeler, Gilles; Prins, Jan M.; Rieger, Armin; Stoeckle, Marcel; Kümmerle, Tim; Bini, Teresa; Ammassari, Adriana; Gilson, Richard; Krznaric, Ivanka; Ristola, Matti; Zangerle, Robert; Handberg, Pia; Antela, Antonio; Allan, Sris; Phillips, Andrew N.; Lundgren, Jens; Pompeyo, V.; Trastoy, M.; Palacio, R.; Gutiérrez, F.; Masiá, M.; Padilla, S.; Robledano, C.; Clotet, B.; Coll, P.; Peña, J.; Estrada, V.; Rodrigo, M.; Santiago, E.; Rivero, A.; Antela, A.; Losada, E.

2016-01-01

IMPORTANCE A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE To evaluate the rate of

Use of a Risk-Stratification Tool in Identification of Potential Adrenal Suppression Preceding Steroid Injection Therapy in Chronic Pain Patients.

Science.gov (United States)

Goel, Aneesh Paul; Nguyen, Vu Huy; Hamill-Ruth, Robin

2015-12-01

Patients who present for steroid injections are not routinely screened for potential hypothalamic-pituitary-adrenal (HPA) axis suppression from previous steroid exposure. Patients often receive various steroid therapies that are not reported by the patient or recorded in available medical records. Yet, HPA axis suppression has been reported with a single intra-articular injection. An IRB-approved quality improvement questionnaire was implemented to comprehensively screen patients for risk of HPA axis suppression secondary to prior and/or concurrent corticosteroid use. This questionnaire was given to adult patients seen in a University Pain Management Clinic, who were being considered for a steroid injection, to define the extent of exposure to corticosteroids either by mouth, topically, inhaled, or systemic/local injection within the past 6 months. Two hundred patients completed the questionnaire. Eighty-nine patients (44.5%) screened positive for significant steroid exposure with a screen score of three or above. The average score for the screen positive group was 6.31 ± 3.47 (range 3-22). Women were 1.9 times more likely to screen positive than men (53.4% vs 27.5%, P suppression. Further testing is necessary to determine if these patients indeed have biochemical evidence of adrenal suppression. Utilization of a screening questionnaire might help identify patients who should be considered for HPA axis testing prior to steroid injections. Wiley Periodicals, Inc.

Expressão do Mg+2, CK, AST e LDH em equinos finalistas de provas de enduro Endurance horses finalists: expression of Mg+2, CK, AST and LDH in horse finalists of endurance race

Directory of Open Access Journals (Sweden)

Juliana V.F. Sales

2013-01-01

Full Text Available Nos últimos anos, o equino atleta vem sendo cada vez mais requerido. Dessa forma, as exigências por alto desempenho têm fomentado o interesse pelo estudo das afecções relacionadas com a fisiopatologia de diversas enfermidades dos equinos. A relação entre o íon magnésio e o exercício físico tem recebido atenção significativa visto que este íon está intimamente relacionado ao tecido muscular estriado esquelético. Além disso, dentre as principais estratégias para a detecção e acompanhamento clínico de lesões musculares, destacam-se a avaliação das atividades das enzimas creatino quinase (CK, lactato desidrogenase (LDH e aspartato aminotransferase (AST. A busca pelo estabelecimento de parâmetros que se relacionam entre si é um fator determinante na compreensão de alterações fisiológicas encontradas diante do esforço em equinos atletas. Desta forma, o presente trabalho teve como objetivo determinar como as concentrações sanguíneas do íon magnésio e as atividades enzimáticas das enzimas CK, LDH e AST comportaram-se em equinos Puro Sangue Árabe finalistas de provas de enduro de 90km e relacionar as possíveis alterações com o tipo de esforço físico desempenhado pelos animais. Foram avaliadas a atividade enzimática das enzimas CK, LDH, AST e a concentração do íon magnésio no exercício em relação ao repouso de 14 equinos clinicamente hígidos da raça Puro Sangue Árabe, sendo 9 machos e 5 fêmeas, com idades variando entre 6 a 12 anos, submetidos a treinamento para enduro e participantes de provas de 90 km. Pode-se observar que as variáveis acima mencionadas sofreram aumento com diferença estatística em relação ao repouso. O exercício físico de enduro determinou a ocorrência de alterações nas atividades enzimáticas das enzimas CK (p≤0,001, LDH (p=0,0001, AST (p=0,0007 e na concentração do íon magnésio (p=0,0004, no exercício em relação ao repouso (p≤0,05. Fato que determinou altera

Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study.

Science.gov (United States)

Cerutti, Bernard; Broers, Barbara; Masetsibi, Motlomelo; Faturiyele, Olatunbosun; Toti-Mokoteli, Likabelo; Motlatsi, Mokete; Bader, Joelle; Klimkait, Thomas; Labhardt, Niklaus D

2016-09-08

Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p women 32.7 %, p suppression. Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. April 28th 2014; NCT02126696 .

Optimising antiresorptive therapies in postmenopausal women: why do we need to give due consideration to the degree of suppression?

Science.gov (United States)

Karsdal, Morten A; Qvist, Per; Christiansen, Claus; Tankó, László B

2006-01-01

Accelerated bone turnover with bone resorption exceeding bone formation is a major mechanism underlying postmenopausal bone loss and hence the development of osteoporosis. Accordingly, inhibition of bone resorption is a rational approach for the prevention of osteoporosis. In this context, the most logical option, hormone replacement therapy, reverses the rate of bone turnover to premenopausal levels, whereas the magnitude of inhibition by amino-bisphosphonates and the recently introduced anti-receptor activator of NFkappaB ligand (RANKL) antibody often exceeds this. As bone turnover has crucial implications for the continuous renewal of bone tissue, the over-suppression of bone turnover has potential consequences for bone quality and strength. Long-term treatment with potent bisphosphonates has recently been associated with osteonecrosis of the jaw and dose-dependent increases in micro-crack accumulation in animals. Although these observations are the subject of ongoing discussions, it is timely to discuss whether the over-suppression of bone turnover below premenopausal levels is really our ultimate goal when defining the success criteria for antiresorptive agents. In this review, the implications of high and excessively low bone turnover of endogenous origin for bone quality, fracture risk and integrity of the jaw are discussed. In addition, animal and clinical research revealing initial findings regarding the potential adverse effects of drug-induced suppression of bone remodeling are summarised. The inhibition of bone resorption, which is either transient between doses (e.g. with calcitonin) or does not exceed premenopausal levels (with hormone replacement therapy or selective estrogen receptor modulators), is preferable because it not only provides similar antifracture efficacy but can also assist in the maintenance of the dynamic repair of micro-cracks/micro-fractures.

AzTEC on ASTE Survey of Submillimeter Galaxies

Science.gov (United States)

Kohno, K.; Tamura, Y.; Hatsukade, B.; Nakanishi, K.; Iono, D.; Takata, T.; Wilson, G. W.; Yun, M. S.; Perera, T.; Austermann, J. E.; Scott, K. S.; Hughes, H.; Aretxaga, I.; Tanaka, K.; Oshima, T.; Yamaguchi, N.; Matsuo, H.; Ezawa, H.; Kawabe, R.

2008-10-01

We have conducted an unprecedented survey of submillimeter galaxies (SMGs) using the 144 pixel bolometer camera AzTEC mounted on the ASTE 10-m dish in Chile. We have already obtained many (>20) wide (typically 12' × 12' or wider) and deep (1 σ sensitivity of 0.5-1.0 mJy) 1.1 mm continuum images of known blank fields and over-density regions/protoclusters across a wide range of redshifts with a spatial resolution of ˜ 30''. It has resulted in the numerous (˜ a few 100, almost equivalent to the total number of the previously known SMGs) new and secure detections of SMGs. In this paper, we present initial results of two selected fields, SSA 22 and AKARI Deep Field South (ADF-S). A significnat clustering of bright SMGs toward the density peak of LAEs is found in SSA 22. We derived the differential and cumulative number counts from the detected sources in ADF-S, which probe the faintest flux densities (down to ˜1 mJy) among 1-mm blank field surveys to date.

Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

Energy Technology Data Exchange (ETDEWEB)

Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S. [Department of Radiology-JPP 3889, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52246 (United States); Luisiri, A. [Cardinal Glennon Children' s Hospital, St. Louis, Missouri (United States); Garibaldi, L.R. [Children' s Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey (United States); St. Barnabas Medical Center, Livingston, New Jersey (United States)

2000-07-01

Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

International Nuclear Information System (INIS)

Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S.; Luisiri, A.; Garibaldi, L.R.

2000-01-01

Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

76 FR 51459 - Office of Commercial Space Transportation (AST); Notice of Availability of the Record of Decision...

Science.gov (United States)

2011-08-18

... Action, FAA/AST could issue, renew, or modify launch operator licenses for Atlas V and Delta IV... the Evolved Expendable Launch Vehicle (EELV) Program, Which Include Atlas V and Delta IV Vehicles, From Cape Canaveral Air Force Station (CCAFS), Florida and Vandenberg Air Force Base (VAFB), California...

HIV-Infected Ugandan Women on Antiretroviral Therapy Maintain HIV-1 RNA Suppression Across Periconception, Pregnancy, and Postpartum Periods.

Science.gov (United States)

Matthews, Lynn T; Ribaudo, Heather B; Kaida, Angela; Bennett, Kara; Musinguzi, Nicholas; Siedner, Mark J; Kabakyenga, Jerome; Hunt, Peter W; Martin, Jeffrey N; Boum, Yap; Haberer, Jessica E; Bangsberg, David R

2016-04-01

HIV-infected women risk sexual and perinatal HIV transmission during conception, pregnancy, childbirth, and breastfeeding. We compared HIV-1 RNA suppression and medication adherence across periconception, pregnancy, and postpartum periods, among women on antiretroviral therapy (ART) in Uganda. We analyzed data from women in a prospective cohort study, aged 18-49 years, enrolled at ART initiation and with ≥1 pregnancy between 2005 and 2011. Participants were seen quarterly. The primary exposure of interest was pregnancy period, including periconception (3 quarters before pregnancy), pregnancy, postpartum (6 months after pregnancy outcome), or nonpregnancy related. Regression models using generalized estimating equations compared the likelihood of HIV-1 RNA ≤400 copies per milliliter, pregnancy, and 89% of postpartum visits, and was more likely during periconception (adjusted odds ratio, 2.15) compared with nonpregnant periods. Average ART adherence was 90% [interquartile range (IQR), 70%-98%], 93% (IQR, 82%-98%), 92% (IQR, 72%-98%), and 88% (IQR, 63%-97%) during nonpregnant, periconception, pregnant, and postpartum periods, respectively. Average adherence pregnancy were virologically suppressed at most visits, with an increased likelihood of suppression and high adherence during periconception follow-up. Increased frequency of 72-hour gaps suggests a need for increased adherence support during postpartum periods.

Comparison of the Influence on the Liver Function Between Thyroid Hormone Withdrawal and rh-TSH Before High-Dose Radioiodine Therapy in Patients with Well-Differentiated Thyroid Cancer

Energy Technology Data Exchange (ETDEWEB)

Han, Yeon-Hee; Lim, Seok Tae; Yun, Kuk-No; Yim, Sung Kyun; Kim, Dong Wook; Jeong, Hwan-Jeong; Sohn, Myung-Hee [Chonbuk National Univ. Medical School and Hospital, Jeonju (Korea, Republic of)

2012-06-15

An elevated thyroid stimulating hormone level (TSH) is essential to stimulate the uptake of radioiodine into thyroid remnants and metastases and metastases of thyroid cancer when a patient under-goes high-dose radioiodine therapy. Nowadays, recombinant human thyroid stimulating hormone (rh-TSH) is increasingly used instead of the classic method of thyroid hormone withdrawal (THW). However, beyond the therapeutic effects, clinical differences between the two methods have not yet been clearly demonstrated. The aim of this work was to investigate the effects of the two methods, especially on liver function. We identified 143 evaluable patients who were further divided into two groups: THW and rh-TSH. We first reviewed the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which were measured during the admission period for total thyroidectomy. We called these liver enzyme levels 'base AST' and 'base ALT.' We also assessed other chemistry profiles, including AST, ALT, total cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB), and triglyceride (TG), which were measured on admission day for high-dose radioiodine therapy. We called these liver enzyme levels 'follow-up AST'and 'follow-up ALT.' We compared the changes in base and follow-up liver enzyme levels and the other chemistry profiles between the two groups. The base AST and base ALT levels of the two groups were within normal range, and there was no significant difference between the two groups. In contrast to these base liver enzyme levels, follow-up AST and ALT levels than did the rh-TSH group. Patients in the THW group. Patients in the THW group also had higher levels of total cholesterol and LDL cholesterol than did the patients in the rh-TSH group. However there were no statistically significant differences in ALP, total bilirubin, and triglyceride levels between the two groups. In this retrospective analysis of liver

Lepton-flavor universality violation in R K and {R}_{D{_{(\\ast )}}} from warped space

Science.gov (United States)

Megías, Eugenio; Quirós, Mariano; Salas, Lindber

2017-07-01

Some anomalies in the processes b → sℓℓ ( ℓ = μ, e) and b\\to cℓ {\\overline{ν}}_{ℓ } ( ℓ = τ, μ, e), in particular in the observables R K and {R}_{D{_{(\\ast )}}} , have been found by the BaBar, LHCb and Belle collaborations, leading to a possible lepton flavor universality violation. If these anomalies were confirmed they would inevitably lead to physics beyond the Standard Model. In this paper we try to accommodate the present anomalies in an extra dimensional theory, solving the naturalness problem of the Standard Model by means of a warped metric with a strong conformality violation near the infra-red brane. The R K anomaly can be accommodated provided that the left-handed bottom quark and muon lepton have some degree of compositeness in the dual theory. The theory is consistent with all electroweak and flavor observables, and with all direct searches of Kaluza-Klein electroweak gauge bosons and gluons. The fermion spectrum, and fermion mixing angles, can be reproduced by mostly elementary right-handed bottom quarks, and tau and muon leptons. Moreover the {R}_{D{_{(\\ast )}}} anomaly requires a strong degree of compositeness for the left-handed tau leptons, which turns out to be in tension with experimental data on the {g}_{τ_L}^Z coupling, possibly unless some degree of fine-tuning is introduced in the fixing of the CKM matrix.

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

Science.gov (United States)

Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

2016-01-01

We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the

CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa.

Science.gov (United States)

Geng, Elvin H; Neilands, Torsten B; Thièbaut, Rodolphe; Bwana, Mwebesa Bosco; Nash, Denis; Moore, Richard D; Wood, Robin; Zannou, Djimon Marcel; Althoff, Keri N; Lim, Poh Lian; Nachega, Jean B; Easterbrook, Philippa J; Kambugu, Andrew; Little, Francesca; Nakigozi, Gertrude; Nakanjako, Damalie; Kiggundu, Valerian; Ki Li, Patrick Chung; Bangsberg, David R; Fox, Matthew P; Prozesky, HansW; Hunt, Peter W; Davies, Mary-Ann; Reynolds, Steven J; Egger, Matthias; Yiannoutsos, Constantin T; Vittinghoff, Eric V; Deeks, Steven G; Martin, Jeffrey N

2015-02-01

Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517–541] in North America, 494/ml (95% CI: 429–559) in West Africa, 515/ml (95% CI: 508–522) in Southern Africa, 503/ml (95% CI: 478–528) in Asia and 437/ml (95% CI: 425–449) in East Africa. CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

BIOCHEMICAL SUBSTANTIATION OF COMBINED THERAPY APPLICATION IN THE ACUTE PHASE OF EXPERIMENTAL HELMINTHIASIS OF ANIMALS

Directory of Open Access Journals (Sweden)

E. A. Grishina

2017-01-01

Full Text Available The purpose of this study was to investigate the influence of the invasion process and different strategies of treatment on some biochemical blood indices of mice infested with Syphacia obvelata and Trichocephalus muris of gastrointestinal tract, in order to optimize etiotropic therapy and improve its efficiency. Materials and methods. In the experiment were used albino mice, divided into the following groups: intact animals (control group; animals infected with Syphacia obvelata; animals infected with Trichocephalus muris; infected animals, who received a single dose of albendazole (7 mg/kg; infected animals, who received a single dose of albendazole (7 mg/kg and gamavit dose intramuscularly (0.3 cm3/kg simultaneously. Blood for the studies was taken from the animals at 1, 3, 7, 10, 14, 17, 21 days after the infection and after drug administration. From biochemical parameters were determined activities of next enzymes: alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyl transferase (γ-GTP and alkaline phosphatase (AP – with kinetic method IFCC. Results. Infecting animals with helminthes caused a noticeable increase in AP and gamma-GTP levels and cytolytic activity of enzymes: ALT and AST compared with intact group. The above-mentioned complex of metabolic changes clearly reveals a disturbance in hepatocyte metabolism that leads to the decrease in detoxifying function of the liver. This can be apparently explained with toxic effects of helminthes waste products. Albendazole mono-therapy in the therapeutic dose (7 mg/kg of mice infected with both Syphacia and Trichocephalus caused an even greater increase in ALT and AST levels and also increased serum levels of alkaline phosphatase and γ-GTP, compared with the control and infected animals, that clearly shows an additional toxic effect from the antihelmintic drug. The use of albendazole in combination with a complex antioxidant “Gamavit” in animals infected with

Multi-hazard Assessment and Scenario Toolbox (MhAST): A Framework for Analyzing Compounding Effects of Multiple Hazards

Science.gov (United States)

Sadegh, M.; Moftakhari, H.; AghaKouchak, A.

2017-12-01

Many natural hazards are driven by multiple forcing variables, and concurrence/consecutive extreme events significantly increases risk of infrastructure/system failure. It is a common practice to use univariate analysis based upon a perceived ruling driver to estimate design quantiles and/or return periods of extreme events. A multivariate analysis, however, permits modeling simultaneous occurrence of multiple forcing variables. In this presentation, we introduce the Multi-hazard Assessment and Scenario Toolbox (MhAST) that comprehensively analyzes marginal and joint probability distributions of natural hazards. MhAST also offers a wide range of scenarios of return period and design levels and their likelihoods. Contribution of this study is four-fold: 1. comprehensive analysis of marginal and joint probability of multiple drivers through 17 continuous distributions and 26 copulas, 2. multiple scenario analysis of concurrent extremes based upon the most likely joint occurrence, one ruling variable, and weighted random sampling of joint occurrences with similar exceedance probabilities, 3. weighted average scenario analysis based on a expected event, and 4. uncertainty analysis of the most likely joint occurrence scenario using a Bayesian framework.

Truth-telling contra perfectionist liberalism: Muslim parrhēsíastes in Denmark

DEFF Research Database (Denmark)

Renders, Johannes

In this paper, I first offer a general outline and reflection on the notion of parrhēsía (truth-telling), as popularized by Foucault. Secondly, I discuss Foucault’s history of problematizations, with comments on what he called “games of truth” and the Cartesian conception of truth-telling. Thirdly......, I sketch a trend in the current Danish public and political sphere, defining the notion of “perfectionist liberalism” and how it translates to the Danish context, including concrete examples and notes on “liberal intolerance arguments”. Lastly, I address the condition of Muslim parrhēsíastes (truth...

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

International Nuclear Information System (INIS)

Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

2015-01-01

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. �

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

Energy Technology Data Exchange (ETDEWEB)

Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

2015-10-15

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. �

Un cinéaste antifasciste à Paris : Slatan Dudow (1934-1939)

OpenAIRE

Trugeon, Mélanie

2011-01-01

Réfugié à Paris après l’arrivée de Hitler au pouvoir en Allemagne, le metteur en scène de théâtre et cinéaste bulgare Slatan Dudow poursuit son travail militant sur scène, à la radio et sur les écrans dans la capitale française jusqu’à son expulsion en 1939-1940 où il trouve alors refuge en Suisse. À partir d’un riche fonds d’archives déposé aux Archives Nationales, inexploité à ce jour, cet article retrace les conditions et les aléas de cette activité artistique et politique, en particulier ...

Effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid

Directory of Open Access Journals (Sweden)

Ya-Ling Wang

2016-09-01

Full Text Available Objective: To investigate the effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid. Methods: A total of 80 patients with dental porcelain crowns at front teeth during February 2013 to February 2016 were randomly divided into cobalt-chromium alloy PFM group (n=40 and gold alloy PFM group (n=40. After 6 months, the amount of gingival crevicular fluid, GI, PD, AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid were recorded and analyzed. Results: There were no differences in amount of gingival crevicular fluid, GI and PD before treatment of the two groups (P>0.05. After treatment, the amount of gingival crevicular fluid, GI and PD of the two groups were significantly higher than before treatment (P0.05. After treatment, the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid of the two groups were significantly higher than before treatment (P<0.05, but that of the gold alloy PFM group were significantly lower than cobalt-chromium alloy PFM group (P<0.05. After treatment, the GP-x level in gingival crevicular fluid of the two groups were significantly lower than before treatment (P<0.05, but that of the gold alloy PFM group were significantly higher than cobalt-chromium alloy PFM group (P<0.05. Conclusions: Gold alloy PFM can significantly reduce the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid, improve the GP-x level in gingival crevicular fluid, shows better biocompatibility and clinical outcomes than cobalt-chromium alloy PFM.

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

Directory of Open Access Journals (Sweden)

Jean-Guy Baril

Full Text Available We reviewed the current literature regarding antiretroviral (ARV-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection.A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations.Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels.The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable

Oropharyngeal flora in patients admitted to the medical intensive care unit: clinical factors and acid suppressive therapy.

Science.gov (United States)

Frandah, Wesam; Colmer-Hamood, Jane; Mojazi Amiri, Hoda; Raj, Rishi; Nugent, Kenneth

2013-05-01

Acid suppression therapy in critically ill patients significantly reduces the incidence of stress ulceration and gastrointestinal (GI) bleeding; however, recent studies suggest that proton pump inhibitors (PPIs) increase the risk of pneumonia. We wanted to test the hypothesis that acid suppressive therapy promotes alteration in the bacterial flora in the GI tract and leads to colonization of the upper airway tract with pathogenic species, potentially forming the biological basis for the observed increased incidence of pneumonia in these patients. This was a prospective observational study on patients (adults 18 years or older) admitted to the medical intensive care unit (MICU) at a tertiary care centre. Exclusion criteria included all patients with a diagnosis of pneumonia at admission, with infection in the upper airway, or with a history of significant dysphagia. Oropharyngeal cultures were obtained on day 1 and days 3 or 4 of admission. We collected data on demographics, clinical information, and severity of the underlying disease using APACHE II scores. There were 110 patients enrolled in the study. The mean age was 49±16 years, 50 were women, and the mean APACHE II score was 9.8 ± 6.5. Twenty per cent of the patients had used a PPI in the month preceding admission. The first oropharyngeal specimen was available in 110 cases; a second specimen at 72-96 h was available in 68 cases. Seventy-five per cent of the patients admitted to the MICU had abnormal flora. In multivariate logistic regression, diabetes mellitus and PPI use were associated with abnormal oral flora on admission. Chronic renal failure and a higher body mass index reduced the frequency of abnormal oral flora on admission. Most critically ill patients admitted to our MICU have abnormal oral flora. Patients with diabetes and a history of recent PPI use are more likely to have abnormal oral flora on admission.

Genetic exchange versus genetic differentiation in a medium-sized inversion of Drosophila: the A2/Ast arrangements of Drosophila subobscura.

Science.gov (United States)

Nóbrega, Clévio; Khadem, Mahnaz; Aguadé, Montserrat; Segarra, Carmen

2008-08-01

Chromosomal inversion polymorphism affects nucleotide variation at loci associated with inversions. In Drosophila subobscura, a species with a rich chromosomal inversion polymorphism and the largest recombinational map so far reported in the Drosophila genus, extensive genetic structure of nucleotide variation was detected in the segment affected by the O(3) inversion, a moderately sized inversion at Muller's element E. Indeed, a strong genetic differentiation all over O(3) and no evidence of a higher genetic exchange in the center of the inversion than at breakpoints were detected. In order to ascertain, whether other polymorphic and differently sized inversions of D. subobscura also exhibited a strong genetic structure, nucleotide variation in 5 gene regions (P236, P275, P150, Sxl, and P125) located along the A(2) inversion was analyzed in A(st) and A(2) chromosomes of D. subobscura. A(2) is a medium-sized inversion at Muller's element A and forms a single inversion loop in heterokaryotypes. The lower level of variation in A(2) relative to A(st) and the significant excess of low-frequency variants at polymorphic sites indicate that nucleotide variation at A(2) is not at mutation-drift equilibrium. The closest region to an inversion breakpoint, P236, exhibits the highest level of genetic differentiation (F(ST)) and of linkage disequilibrium (LD) between arrangements and variants at nucleotide polymorphic sites. The remaining 4 regions show a higher level of genetic exchange between A(2) and A(st) chromosomes than P236, as revealed by F(ST) and LD estimates. However, significant genetic differentiation between the A(st) and A(2) arrangements was detected not only at P236 but also in the other 4 regions separated from the nearest breakpoint by 1.2-2.9 Mb. Therefore, the extent of genetic exchange between arrangements has not been high enough to homogenize nucleotide variation in the center of the A(2) inversion. A(2) can be considered a typical successful inversion

Antiretroviral therapy, immune suppression and renal impairment in HIV-positive persons

DEFF Research Database (Denmark)

Nielsen, Lene Ryom; Mocroft, Amanda; Lundgren, Jens D

2014-01-01

The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field.......The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field....

Implementation and evaluation of the 5As framework of obesity management in primary care: design of the 5As Team (5AsT) randomized control trial.

Science.gov (United States)

Campbell-Scherer, Denise L; Asselin, Jodie; Osunlana, Adedayo M; Fielding, Sheri; Anderson, Robin; Rueda-Clausen, Christian F; Johnson, Jeffrey A; Ogunleye, Ayodele A; Cave, Andrew; Manca, Donna; Sharma, Arya M

2014-06-19

Obesity is a pressing public health concern, which frequently presents in primary care. With the explosive obesity epidemic, there is an urgent need to maximize effective management in primary care. The 5As of Obesity Management™ (5As) are a collection of knowledge tools developed by the Canadian Obesity Network. Low rates of obesity management visits in primary care suggest provider behaviour may be an important variable. The goal of the present study is to increase frequency and quality of obesity management in primary care using the 5As Team (5AsT) intervention to change provider behaviour. The 5AsT trial is a theoretically informed, pragmatic randomized controlled trial with mixed methods evaluation. Clinic-based multidisciplinary teams (RN/NP, mental health, dietitians) will be randomized to control or the 5AsT intervention group, to participate in biweekly learning collaborative sessions supported by internal and external practice facilitation. The learning collaborative content addresses provider-identified barriers to effective obesity management in primary care. Evidence-based shared decision making tools will be co-developed and iteratively tested by practitioners. Evaluation will be informed by the RE-AIM framework. The primary outcome measure, to which participants are blinded, is number of weight management visits/full-time equivalent (FTE) position. Patient-level outcomes will also be assessed, through a longitudinal cohort study of patients from randomized practices. Patient outcomes include clinical (e.g., body mass index [BMI], blood pressure), health-related quality of life (SF-12, EQ5D), and satisfaction with care. Qualitative data collected from providers and patients will be evaluated using thematic analysis to understand the context, implementation and effectiveness of the 5AsT program. The 5AsT trial will provide a wide range of insights into current practices, knowledge gaps and barriers that limit obesity management in primary practice

Antiretroviral therapy: current drugs.

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Pau, Alice K; George, Jomy M

2014-09-01

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

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Alessandra Ruggiero

2015-09-01

Conclusions: The observed positive association between integrated HIV-1 DNA load and frequency of CD8+DR/DP/DQ+ cells indicates that a close correlation between HIV persistence and immune activation continues during consistently suppressive therapy. The inducers of the distinct activation profile warrant further investigation.

Dynamics of Interocular Suppression in Amblyopic Children during Electronically Monitored Occlusion Therapy: First Insight.

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Kehrein, Stephan; Kohnen, Thomas; Fronius, Maria

2016-06-01

Interocular suppression is assumed to be the mechanism leading to impaired visual acuity, especially in strabismic amblyopia. Little is known about the dynamics of suppression during treatment. The aim of our study was to assess the development of the depth of suppression and its relation to changes in visual acuity during electronically monitored occlusion treatment. In a prospective pilot study, 15 amblyopes (8 with and 7 without strabismus) aged 5 to 16 years (mean 10.24 years) were examined before initiation of patching and then every 3 to 6 weeks for 4 months. To quantify suppression, a red filter ladder (Sbisa bar) was used, attenuating the image of the dominant eye until the patients reported a binocular perception (diplopia, rivalry, color mixture) or a change in eye dominance. Acuity was assessed with crowded Landolt rings. Daily occlusion was recorded using occlusion dose monitors. The depth of interocular suppression showed a biphasic change: it increased significantly during the first month (P=0.02), while visual acuity improved (mean 0.14 log units ±0.13; Pocclusion and suppression changes was not statistically significant. This first insight into the functional changes during electronically monitored patching suggests a complex relationship between visual acuity and interocular suppression that seems to be influenced by the presence of strabismus. Knowledge of the dynamics of interocular suppression is crucial for enhancing the outcome of occlusion treatment and also for the evaluation of its future role compared to emerging dichoptic treatments.

Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study

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Bernard Cerutti

2016-09-01

Full Text Available Abstract Background Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART. Studies examining their association with viral suppression in rural Africa are, however, scarce. Methods This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Results Among 1,388 adult patients (69 % women, 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001. The prevalence of depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001. Both alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77 and alcohol use disorder (2.73, 95 % CI: 1.68-4.42 were significantly associated with poor adherence. There was, however, no significant association with viral suppression. Conclusions Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. Trial registration April 28th 2014; NCT02126696 .

Long-term results of golimumab therapy for rheumatoid arthritis. Therapy compliance issues

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N. V. Chichasova

2016-01-01

Full Text Available The goal of therapy for rheumatoid arthritis (RA is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

The regional extent of suppression: strabismics versus nonstrabismics.

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Babu, Raiju Jacob; Clavagnier, Simon R; Bobier, William; Thompson, Benjamin; Hess, Robert F

2013-10-09

Evidence is accumulating that suppression may be the cause of amblyopia rather than a secondary consequence of mismatched retinal images. For example, treatment interventions that target suppression may lead to better binocular and monocular outcomes. Furthermore, it has recently been demonstrated that the measurement of suppression may have prognostic value for patching therapy. For these reasons, the measurement of suppression in the clinic needs to be improved beyond the methods that are currently available, which provide a binary outcome. We describe a novel quantitative method for measuring the regional extent of suppression that is suitable for clinical use. The method involves a dichoptic perceptual matching procedure at multiple visual field locations. We compare a group of normal controls (mean age: 28 ± 5 years); a group with strabismic amblyopia (four with microesotropia, five with esotropia, and one with exotropia; mean age: 35 ± 10 years); and a group with nonstrabismic anisometropic amblyopia (mean age: 33 ± 12 years). The extent and magnitude of suppression was similar for observers with strabismic and nonstrabismic amblyopia. Suppression was strongest within the central field and extended throughout the 20° field that we measured. Suppression extends throughout the central visual field in both strabismic and anisometropic forms of amblyopia. The strongest suppression occurs within the region of the visual field corresponding to the fovea of the fixing eye.

Angular analysis of $B^0 \\to K^\\ast(892)^0 \\ell^+ \\ell^-$

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Abdesselam, A.; Adamczyk, K.; Aihara, H.; Al Said, S.; Arinstein, K.; Arita, Y.; Asner, D.M.; Aso, T.; Atmacan, H.; Aulchenko, V.; Aushev, T.; Ayad, R.; Aziz, T.; Babu, V.; Badhrees, I.; Bahinipati, S.; Bakich, A.M.; Bala, A.; Ban, Y.; Bansal, V.; Barberio, E.; Barrett, M.; Bartel, W.; Bay, A.; Bedny, I.; Behera, P.; Belhorn, M.; Belous, K.; Besson, D.; Bhardwaj, V.; Bhuyan, B.; Biswal, J.; Bloomfield, T.; Blyth, S.; Bobrov, A.; Bondar, A.; Bonvicini, G.; Bookwalter, C.; Boulahouache, C.; Bozek, A.; Bračko, M.; Breibeck, F.; Brodzicka, J.; Browder, T.E.; Waheed, E.; Červenkov, D.; Chang, M. -C.; Chang, P.; Chao, Y.; Chekelian, V.; Chen, A.; Chen, K. -F.; Chen, P.; Cheon, B.G.; Chilikin, K.; Chistov, R.; Cho, K.; Chobanova, V.; Choi, S. -K.; Choi, Y.; Cinabro, D.; Crnkovic, J.; Dalseno, J.; Danilov, M.; Dash, N.; Di Carlo, S.; Dingfelder, J.; Doležal, Z.; Dossett, D.; Drásal, Z.; Drutskoy, A.; Dubey, S.; Dutta, D.; Dutta, K.; Eidelman, S.; Epifanov, D.; Esen, S.; Farhat, H.; Fast, J.E.; Feindt, M.; Ferber, T.; Frey, A.; Frost, O.; Fulsom, B.G.; Gaur, V.; Gabyshev, N.; Ganguly, S.; Garmash, A.; Getzkow, D.; Gillard, R.; Giordano, F.; Glattauer, R.; Goh, Y.M.; Goldenzweig, P.; Golob, B.; Greenwald, D.; Grosse Perdekamp, M.; Grygier, J.; Grzymkowska, O.; Guo, H.; Haba, J.; Hamer, P.; Han, Y.L.; Hara, K.; Hara, T.; Hasegawa, Y.; Hasenbusch, J.; Hayasaka, K.; Hayashii, H.; He, X.H.; Heck, M.; Hedges, M.T.; Heffernan, D.; Heider, M.; Heller, A.; Higuchi, T.; Himori, S.; Hirose, S.; Horiguchi, T.; Hoshi, Y.; Hoshina, K.; Hou, W. -S.; Hsiung, Y.B.; Hsu, C. -L.; Huschle, M.; Hyun, H.J.; Igarashi, Y.; Iijima, T.; Imamura, M.; Inami, K.; Inguglia, G.; Ishikawa, A.; Itagaki, K.; Itoh, R.; Iwabuchi, M.; Iwasaki, M.; Iwasaki, Y.; Iwata, S.; Jacobs, W.W.; Jaegle, I.; Jeon, H.B.; Joffe, D.; Jones, M.; Joo, K.K.; Julius, T.; Kakuno, H.; Kang, J.H.; Kang, K.H.; Kapusta, P.; Kataoka, S.U.; Kato, E.; Kato, Y.; Katrenko, P.; Kawai, H.; Kawasaki, T.; Keck, T.; Kichimi, H.; Kiesling, C.; Kim, B.H.; Kim, D.Y.; Kim, H.J.; Kim, H. -J.; Kim, J.B.; Kim, J.H.; Kim, K.T.; Kim, M.J.; Kim, S.H.; Kim, S.K.; Kim, Y.J.; Kinoshita, K.; Kleinwort, C.; Klucar, J.; Ko, B.R.; Kobayashi, N.; Koblitz, S.; Kodyš, P.; Koga, Y.; Korpar, S.; Kotchetkov, D.; Kouzes, R.T.; Križan, P.; Krokovny, P.; Kronenbitter, B.; Kuhr, T.; Kumar, R.; Kumita, T.; Kurihara, E.; Kuroki, Y.; Kuzmin, A.; Kvasnička, P.; Kwon, Y. -J.; Lai, Y. -T.; Lange, J.S.; Lee, D.H.; Lee, I.S.; Lee, S. -H.; Leitgab, M.; Leitner, R.; Levit, D.; Lewis, P.; Li, C.H.; Li, H.; Li, J.; Li, L.; Li, X.; Li, Y.; Li Gioi, L.; Libby, J.; Limosani, A.; Liu, C.; Liu, Y.; Liu, Z.Q.; Liventsev, D.; Loos, A.; Louvot, R.; Lubej, M.; Lukin, P.; Luo, T.; MacNaughton, J.; Masuda, M.; Matsuda, T.; Matvienko, D.; Matyja, A.; McOnie, S.; Mikami, Y.; Miyabayashi, K.; Miyachi, Y.; Miyake, H.; Miyata, H.; Miyazaki, Y.; Mizuk, R.; Mohanty, G.B.; Mohanty, S.; Mohapatra, D.; Moll, A.; Moon, H.K.; Mori, T.; Morii, T.; Moser, H. -G.; Müller, T.; Muramatsu, N.; Mussa, R.; Nagamine, T.; Nagasaka, Y.; Nakahama, Y.; Nakamura, I.; Nakamura, K.R.; Nakano, E.; Nakano, H.; Nakano, T.; Nakao, M.; Nakayama, H.; Nakazawa, H.; Nanut, T.; Nath, K.J.; Natkaniec, Z.; Nayak, M.; Nedelkovska, E.; Negishi, K.; Neichi, K.; Ng, C.; Niebuhr, C.; Niiyama, M.; Nisar, N.K.; Nishida, S.; Nishimura, K.; Nitoh, O.; Nozaki, T.; Ogawa, A.; Ogawa, S.; Ohshima, T.; Okuno, S.; Olsen, S.L.; Ono, Y.; Onuki, Y.; Ostrowicz, W.; Oswald, C.; Ozaki, H.; Pakhlov, P.; Pakhlova, G.; Pal, B.; Palka, H.; Panzenböck, E.; Park, C. -S.; Park, C.W.; Park, H.; Park, K.S.; Paul, S.; Peak, L.S.; Pedlar, T.K.; Peng, T.; Pesántez, L.; Pestotnik, R.; Peters, M.; Petrič, M.; Piilonen, L.E.; Poluektov, A.; Prasanth, K.; Prim, M.; Prothmann, K.; Pulvermacher, C.; Purohit, M.V.; Rauch, J.; Reisert, B.; Ribežl, E.; Ritter, M.; Röhrken, M.; Rorie, J.; Rostomyan, A.; Rozanska, M.; Rummel, S.; Ryu, S.; Sahoo, H.; Saito, T.; Sakai, K.; Sakai, Y.; Sandilya, S.; Santel, D.; Santelj, L.; Sanuki, T.; Sasao, N.; Sato, Y.; Savinov, V.; Schlüter, T.; Schneider, O.; Schnell, G.; Schönmeier, P.; Schram, M.; Schwanda, C.; Schwartz, A.J.; Schwenker, B.; Seidl, R.; Seino, Y.; Semmler, D.; Senyo, K.; Seon, O.; Seong, I.S.; Sevior, M.E.; Shang, L.; Shapkin, M.; Shebalin, V.; Shen, C.P.; Shibata, T. -A.; Shibuya, H.; Shinomiya, S.; Shiu, J. -G.; Shwartz, B.; Sibidanov, A.; Simon, F.; Singh, J.B.; Sinha, R.; Smerkol, P.; Sohn, Y. -S.; Sokolov, A.; Soloviev, Y.; Solovieva, E.; Stanič, S.; Starič, M.; Steder, M.; Strube, J.F.; Stypula, J.; Sugihara, S.; Sugiyama, A.; Sumihama, M.; Sumisawa, K.; Sumiyoshi, T.; Suzuki, K.; Suzuki, S.; Suzuki, S.Y.; Suzuki, Z.; Takeichi, H.; Takizawa, M.; Tamponi, U.; Tanaka, M.; Tanaka, S.; Tanida, K.; Taniguchi, N.; Taylor, G.N.; Tenchini, F.; Teramoto, Y.; Tikhomirov, I.; Trabelsi, K.; Trusov, V.; Tse, Y.F.; Tsuboyama, T.; Uchida, M.; Uchida, T.; Uehara, S.; Ueno, K.; Uglov, T.; Unno, Y.; Uno, S.; Uozumi, S.; Urquijo, P.; Ushiroda, Y.; Usov, Y.; Vahsen, S.E.; Van Hulse, C.; Vanhoefer, P.; Varner, G.; Varvell, K.E.; Vervink, K.; Vinokurova, A.; Vorobyev, V.; Vossen, A.; Wagner, M.N.; Wang, C.H.; Wang, J.; Wang, M. -Z.; Wang, P.; Wang, X.L.; Watanabe, M.; Watanabe, Y.; Wedd, R.; Wehle, S.; White, E.; Wiechczynski, J.; Williams, K.M.; Won, E.; Yabsley, B.D.; Yamada, S.; Yamamoto, H.; Yamaoka, J.; Yamashita, Y.; Yamauchi, M.; Yashchenko, S.; Ye, H.; Yelton, J.; Yook, Y.; Yuan, C.Z.; Yusa, Y.; Zhang, C.C.; Zhang, L.M.; Zhang, Z.P.; Zhao, L.; Zhilich, V.; Zhukova, V.; Zhulanov, V.; Ziegler, M.; Zivko, T.; Zupanc, A.; Zwahlen, N.; Zyukova, O.

2016-01-01

We present a measurement of angular observables, $P_4'$, $P_5'$, $P_6'$, $P_8'$, in the decay $B^0 \\to K^\\ast(892)^0 \\ell^+ \\ell^-$, where $\\ell^+\\ell^-$ is either $e^+e^-$ or $\\mu^+\\mu^-$. The analysis is performed on a data sample corresponding to an integrated luminosity of $711~\\mathrm{fb}^{-1}$ containing $772\\times 10^{6}$ $B\\bar B$ pairs, collected at the $\\Upsilon(4S)$ resonance with the Belle detector at the asymmetric-energy $e^+e^-$ collider KEKB. Four angular observables, $P_{4,5,6,8}'$ are extracted in five bins of the invariant mass squared of the lepton system, $q^2$. We compare our results for $P_{4,5,6,8}'$ with Standard Model predictions including the $q^2$ region in which the LHCb collaboration reported the so-called $P_5'$ anomaly.

Quantitative measurement of interocular suppression in anisometropic amblyopia: a case-control study.

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Li, Jinrong; Hess, Robert F; Chan, Lily Y L; Deng, Daming; Yang, Xiao; Chen, Xiang; Yu, Minbin; Thompson, Benjamin

2013-08-01

The aims of this study were to assess (1) the relationship between interocular suppression and visual function in patients with anisometropic amblyopia, (2) whether suppression can be simulated in matched controls using monocular defocus or neutral density filters, (3) the effects of spectacle or rigid gas-permeable contact lens correction on suppression in patients with anisometropic amblyopia, and (4) the relationship between interocular suppression and outcomes of occlusion therapy. Case-control study (aims 1-3) and cohort study (aim 4). Forty-five participants with anisometropic amblyopia and 45 matched controls (mean age, 8.8 years for both groups). Interocular suppression was assessed using Bagolini striated lenses, neutral density filters, and an objective psychophysical technique that measures the amount of contrast imbalance between the 2 eyes that is required to overcome suppression (dichoptic motion coherence thresholds). Visual acuity was assessed using a logarithm minimum angle of resolution tumbling E chart and stereopsis using the Randot preschool test. Interocular suppression assessed using dichoptic motion coherence thresholds. Patients exhibited significantly stronger suppression than controls, and stronger suppression was correlated significantly with poorer visual acuity in amblyopic eyes. Reducing monocular acuity in controls to match that of cases using neutral density filters (luminance reduction) resulted in levels of interocular suppression comparable with that in patients. This was not the case for monocular defocus (optical blur). Rigid gas-permeable contact lens correction resulted in less suppression than spectacle correction, and stronger suppression was associated with poorer outcomes after occlusion therapy. Interocular suppression plays a key role in the visual deficits associated with anisometropic amblyopia and can be simulated in controls by inducing a luminance difference between the eyes. Accurate quantification of suppression

Assessment of adjuvant ademetionine therapy for the bilirubin metabolism and target organ function of neonatal jaundice

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Fang Xu

2017-11-01

Full Text Available Objective: To study the effect of adjuvant ademetionine (SAMe therapy on the bilirubin metabolism and target organ function of neonatal jaundice. Methods: A total of 68 children who were diagnosed with neonatal jaundice in Hubei Jianghan Oilfield General Hospital between March 2015 and April 2017 were selected as the research subjects and randomly divided into the SAMe group who received ademetionine combined with blue ray irradiation and the control group who received blue ray irradiation. The serum contents of bilirubin metabolism indexes and target organ injury markers before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of both groups were lower than those before treatment, and serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of SAMe group were lower than those of control group. Conclusion: Adjuvant ademetionine therapy can improve the bilirubin metabolism of neonatal jaundice and reduce the central nerve, myocardial and liver injury.

Antiretroviral treatment switch strategies for lowering the costs of antiretroviral therapy in subjects with suppressed HIV-1 viremia in Spain

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Llibre JM

2013-05-01

Full Text Available Josep M Llibre,1,2 Gloria Cardona,3 José R Santos,2 Angels Andreu,3 Josep O Estrada,4 Jordi Ara,4 Xavier Bonafont,3 Bonaventura Clotet1,21HIV Unit, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 2Lluita contra la SIDA Foundation, Badalona, Barcelona, Spain; 3Hospital Pharmacy, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 4Hospital Management, University Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainBackground: The current economic recession in European countries has forced governments to design emergency measures to reduce spending on drugs, including antiretroviral therapy (ART. Switching antiretroviral drugs for others that have the same efficacy and safety profile at a lower cost (cost-reduction measures, CRM could prove to be a valid means of generating savings.Methods: Descriptive study of prospective consensus-based CRM undertaken in 2011 in a Catalonian hospital HIV unit among patients with prolonged plasma HIV-1 RNA <50 copies/mL.Results: During the study period, we made 673 switches (87.5% more than the previous year, of which 378 (56.2% were CRM (16% of all patients treated, leading to a savings of €87,410/month. Switching tenofovir/emtricitabine for abacavir/lamivudine was the most common CRM (129, 31.3%, followed by simplification to boosted protease inhibitor monotherapy (bPImono, 102, 26%. The CRM that generated the greatest saving were switching to bPImono (38%, withdrawal or replacement of raltegravir (24%, switching tenofovir/emtricitabine for abacavir/lamivudine (13%, and switching to nevirapine (5%. Cost savings with CRM were slightly higher than those achieved with medication paid for by clinical trial sponsors (€80,333/month or through discount arrangements (€76,389/month.Conclusion: Proactively switching antiretroviral therapy in selected treated patients with sustained virological suppression can generate significant cost savings in pharmacy spending in

TRH and T3 suppression tests after 131I therapy of thyrotoxicosis

International Nuclear Information System (INIS)

Tamai, Hajime; Tsushimi, Takashi; Shizume, Kazuo; Kuma, Kanji; Suematsu, Hiroyuki.

1976-01-01

TRH and T 3 suppression tests were performed on patients (124 cases) with Graves' disease who underwent radiotherapy. TRH test was performed at 4 - 6 months (Group I), 6 - 12 months (Group II), 12 - 24 months (Group III) and 24 - 50 months (Group IV) after final radiotherapy, and T 3 suppression test was performed just after each TRH test. Among 124 patients in Group I to IV who were clinically euthyroid and whose T 3 -RU and T 4 values were normal, compared with other groups, Group IV (2 - 4.2 Y) showed a significantly higher percentage of positive responses to both TRH and T 3 suppression tests. However, among 49 of 124 patients whose T 3 was also normal, there were no significant differences between the groups. The value of triiodothyronine was above the normal range in many cases up to 2 years after radiotherapy (in Group I, II, III). There were no significant differences in the percentage of hyperresponses between any of the four groups. Half of the patients who showed positive responses to TRH test showed exaggerated responses. In all cases when the responses to TRH and T 3 suppression tests changed from negative to positive, thyroxine and triiodothyronine concentrations must be within the normal range. In particular, the major determinant seems to be the value of triiodothyronine. As in more than 30% of cases TRH and T 3 suppression tests remained negative even though their T 3 -RU, T 4 , T 3 , values became normal after radiotherapy, the regulation of hypothalamo-hypophyseal thyroid axis do not always return to normal even though circulating thyroidal hormone level return to an euthyroid state. (J.P.N.)

Chk1 suppressed cell death

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Meuth Mark

2010-09-01

Full Text Available Abstract The role of Chk1 in the cellular response to DNA replication stress is well established. However recent work indicates a novel role for Chk1 in the suppression of apoptosis following the disruption of DNA replication or DNA damage. This review will consider these findings in the context of known pathways of Chk1 signalling and potential applications of therapies that target Chk1.

β-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1 diabetes in NOD mice.

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Johnson, Mark C; Garland, Alaina L; Nicolson, Sarah C; Li, Chengwen; Samulski, R Jude; Wang, Bo; Tisch, Roland

2013-11-01

Interleukin-2 (IL-2) is a critical cytokine for the homeostasis and function of forkhead box p3-expressing regulatory T cells (Foxp3(+)Tregs). Dysregulation of the IL-2-IL-2 receptor axis is associated with aberrant Foxp3(+)Tregs and T cell-mediated autoimmune diseases such as type 1 diabetes. Treatment with recombinant IL-2 has been reported to enhance Foxp3(+)Tregs and suppress different models of autoimmunity. However, efficacy of IL-2 therapy is dependent on achieving sufficient levels of IL-2 to boost tissue-resident Foxp3(+)Tregs while avoiding the potential toxic effects of systemic IL-2. With this in mind, adeno-associated virus (AAV) vector gene delivery was used to localize IL-2 expression to the islets of NOD mice. Injection of a double-stranded AAV vector encoding IL-2 driven by a mouse insulin promoter (dsAAVmIP-IL2) increased Foxp3(+)Tregs in the islets but not the draining pancreatic lymph nodes. Islet Foxp3(+)Tregs in dsAAVmIP-IL2-treated NOD mice exhibited enhanced fitness marked by increased expression of Bcl-2, proliferation, and suppressor function. In contrast, ectopic IL-2 had no significant effect on conventional islet-infiltrating effector T cells. Notably, β-cell-specific IL-2 expression suppressed late preclinical type 1 diabetes in NOD mice. Collectively, these findings demonstrate that β-cell-specific IL-2 expands an islet-resident Foxp3(+)Tregs pool that effectively suppresses ongoing type 1 diabetes long term.

Celecoxib Ameliorates Non-Alcoholic Steatohepatitis in Type 2 Diabetic Rats via Suppression of the Non-Canonical Wnt Signaling Pathway Expression

Science.gov (United States)

Tian, Feng; Zhang, Ya Jie; Li, Yu; Xie, Ying

2014-01-01

Our aim was to test whether pharmacological inhibition of cycloxygenase-2 (COX-2) reverses non-alcoholic steatohepatitis (NASH) in type 2 diabetes mellitus (T2DM) rats via suppression of the non-canonical Wnt signaling pathway expression. Twenty-four male Sprague-Dawley rats were randomly distributed to two groups and were fed with a high fat and sucrose (HF-HS) diet or a normal chow diet, respectively. After four weeks, rats fed with a HF-HS diet were made diabetic with low-dose streptozotocin. At the 9th week the diabetic rats fed with a HF-HS diet or the non-diabetic rats fed with a normal chow diet were further divided into two subgroups treated with vehicle or celecoxib (a selective COX-2 inhibitor, 10 mg/Kg/day, gavage) for the last 4 weeks, respectively. At the end of the 12th week, rats were anesthetized. NASH was assessed by histology. Related cytokine expression was measured at both the protein and gene levels through immunohistochemistry (IHC), Western blot and real-time PCR. T2DM rats fed with a HF-HS diet developed steatohepatitis and insulin resistance associated with elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin levels and the non-alcoholic fatty liver disease (NAFLD) activity score (NAS). The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 were all significantly increased in the T2DM-NASH group compared with the control and control-cele group. Hepatic injury was improved by celecoxib in T2DM-NASH-Cele group indicated by reduced serum ALT and AST levels and hepatic inflammation was reduced by celecoxib showed by histology and the NAFLD activity score (NAS). Serum related metabolic parameters, HOMA-IR and insulin sensitivity index were all improved by celecoxib. The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 expression were all suppressed by celecoxib in T2DM-NASH-Cele group. The results of the present study indicated that celecoxib ameliorated NASH in T2DM rats via suppression of the non-canonical Wnt

Relationship between hunger, adherence to antiretroviral therapy and plasma HIV RNA suppression among HIV-positive illicit drug users in a Canadian setting.

Science.gov (United States)

Anema, Aranka; Kerr, Thomas; Milloy, M-J; Feng, Cindy; Montaner, Julio S G; Wood, Evan

2014-04-01

Food insecurity may be a barrier to achieving optimal HIV treatment-related outcomes among illicit drug users. This study therefore, aimed to assess the impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among illicit drug users receiving antiretroviral therapy (ART). A cross-sectional Multivariate logistic regression model was used to assess the potential relationship between hunger and plasma HIV RNA suppression. A sample of n = 406 adults was derived from a community-recruited open prospective cohort of HIV-positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241 (59.4%) had plasma HIV RNA hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio = 0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate analyses, this association was no longer significant after controlling for socio-demographic, behavioral, and clinical characteristics, including 95% adherence (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate models stratified by 95% adherence found that the direction and magnitude of this association was not significantly altered by the adherence level. Hunger was common among illicit drug users in this setting. Although, there was an association between hunger and lower likelihood of plasma HIV RNA suppression, this did not persist in adjusted analyses. Further research is warranted to understand the social-structural, policy, and physical factors shaping the HIV outcomes of illicit drug users.

Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study.

Science.gov (United States)

Ceriotti, Ferruccio; Henny, Joseph; Queraltó, Josep; Ziyu, Shen; Özarda, Yeşim; Chen, Baorong; Boyd, James C; Panteghini, Mauro

2010-11-01

Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC-recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18-85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 μkat/L), allowing a single RI of 11-34 U/L (0.18-0.57 μkat/L) to be defined. Interregional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8-41 U/L (0.13-0.68 μkat/L) for females and 9-59 U/L (0.15-0.99 μkat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6-40 U/L (0.11-0.66 μkat/L) for females and 12-68 U/L (0.20- 1.13 μkat/L) for males, respectively. For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is

Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

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Lokender Kumar

Full Text Available Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP and inflammatory cytokines (MIP-2, IL-6 and TNF-α were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2 indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti

Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

Science.gov (United States)

Kumar, Lokender; Chhibber, Sanjay; Harjai, Kusum

2014-01-01

Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti

Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1.

Science.gov (United States)

Drusano, G L; Louie, Arnold; MacGowan, Alasdair; Hope, William

2015-12-28

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens like Pseudomonas aeruginosa, Acinetobacter spp., and multidrug-resistant (MDR) Enterobacteriaceae. These lessons need to be applied to our old drugs to preserve them as well and need to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a corresponding resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2.

Science.gov (United States)

Drusano, G L; Hope, William; MacGowan, Alasdair; Louie, Arnold

2015-12-28

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens like Pseudomonas aeruginosa, Acinetobacter spp., and multidrug-resistant (MDR) Enterobacteriaceae. These lessons need to be applied to our old drugs as well to preserve them and to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Integrated Variable-Fidelity Tool Set for Modeling and Simulation of Aeroservothermoelasticity-Propulsion (ASTE-P) Effects for Aerospace Vehicles Ranging From Subsonic to Hypersonic Flight, Phase II

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National Aeronautics and Space Administration — The proposed research program aims at developing a variable-fidelity software tool set for aeroservothermoelastic-propulsive (ASTE-P) modeling that can be routinely...

Integrated Variable-Fidelity Tool Set For Modeling and Simulation of Aeroservothermoelasticity -Propulsion (ASTE-P) Effects For Aerospace Vehicles Ranging From Subsonic to Hypersonic Flight, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — The proposed research program aims at developing a variable-fidelity software tool set for aeroservothermoelastic-propulsive (ASTE-P) modeling that can be routinely...

Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

International Nuclear Information System (INIS)

McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

1987-01-01

The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently

Serum thyrotropin (TSH) levels in patients with suppressed pituitary function

International Nuclear Information System (INIS)

Vasavada, P.; Chen, I.; Maxon, H.; Barnes, E.; Sperling, M.

1984-01-01

The diagnosis of borderline hyperthyroidism is difficult. A sensitive radioimmunoassay capable of detecting subnormal levels of serum TSH may be of value in confirming this diagnosis because of the suppressed pituitary function in this disease state. This sensitive assay may also be useful in monitoring the suppression of pituitary function in thyroid cancer patients receiving thyroid hormone therapy. A sensitive radioimmunoassay capable of detecting serum TSH levels as low as 0.25 μU/m1 with coefficients of variation less than 17.2% was used to measure serum TSH levels in 80 healthy subjects, 44 hyperthyroid patients, and 25 athyrotic thyroid cancer patients on daily suppressive doses of thyroxine. All healthy subjects had detectable TSH levels with a mean value of 1.17 and two standard deviation ranges of 0.41 - 2.70 μU/m1 (lognormal distribution). Although the mean +-1 SEM value of 0.63 +- 0.003 μUm1 for hyperthyroid patients and 0.76 +- 0.08 μU/ml for thyroid cancer patients were significantly lower than that of healthy subjects (t-test, p<0.05), subnormal levels of serum TSH were found in only 28.6% (12/42) and 24% (6/25) of hyperthyroid and thyroid cancer patients, respectively. TSH stimulation tests performed in 6 of the cancer patients all gave suppressed responses. Because of considerable overlap, serum TSH levels alone cannot distinguish hyperthyroidsm from euthyroidism. However, a sensitive TSH radioimmunoassay such as the one described here may be of value in evaluating the extent of pituitary suppression in thyroid cancer therapy

Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma.

Science.gov (United States)

Mark, Tomer; Stern, Jessica; Furst, Jessica R; Jayabalan, David; Zafar, Faiza; LaRow, April; Pearse, Roger N; Harpel, John; Shore, Tsiporah; Schuster, Michael W; Leonard, John P; Christos, Paul J; Coleman, Morton; Niesvizky, Ruben

2008-07-01

A total of 28 treatment-naïve patients with stage II or III multiple myeloma (MM) were treated with the combination of clarithromycin, lenalidomide, and dexamethasone (BiRD). Stem cells were collected following granulocyte-colony stimulating factor (G-CSF) or cyclophosphamide (Cy) plus G-CSF mobilization at maximum response. Sufficient stem cells for 2 autologous stem cell transplants were collected from all patients mobilized with Cy plus G-CSF, versus 33% mobilized with G-CSF alone (P < .0001). The duration of prior lenalidomide therapy did not correlate with success of stem cell harvests (P = .91). In conclusion, Cy can be added to G-CSF for stem cell mobilization to successfully overcome the suppressive effect of prior treatment with lenalidomide.

Novel, selective vitamin D analog suppresses parathyroid hormone in uremic animals and postmenopausal women.

Science.gov (United States)

Zella, Julia B; Plum, Lori A; Plowchalk, David R; Potochoiba, Michael; Clagett-Dame, Margaret; DeLuca, Hector F

2014-01-01

The use of 1α-hydroxylated vitamin D therapy to control secondary hyperparathyroidism in renal failure patients has been a success story, culminating with the demonstration of increased life expectancy in patients treated with these compounds. However, hypercalcemic episodes have been a recurrent problem with these therapies and have resulted in the added use of calcium mimetics. Clearly there is good reason to search for improved vitamin D therapy. In our inventory of vitamin D compounds, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) surfaced as a potential candidate. This was based on its preferential localization in the parathyroid gland and a clear suppression of serum parathyroid hormone (PTH) levels without a change in serum calcium in a clinical trial in postmenopausal women. 2MD has now been tested in the rat 5/6-nephrectomy model of renal failure, and in postmenopausal women to determine if it can suppress serum PTH at doses that do not elevate serum calcium and serum phosphorus concentrations. Daily oral treatment of uremic rats on 2.5 ng/bw/day of 2MD dramatically suppressed PTH without a change in serum calcium or serum phosphorus. Further, PTH was suppressed in postmenopausal women after only 3 daily oral doses of 2MD that continued for 4 weeks with no change in serum calcium or serum phosphorus. These results coupled with a pharmacokinetic half-life of ~24 h suggest that 2MD given either daily or at the time of dialysis may be a superior therapy for secondary hyperparathyroidism in chronic renal failure patients.

Expressão do Mg+2, CK, AST e LDH em equinos finalistas de provas de enduro

Directory of Open Access Journals (Sweden)

Juliana V.F. Sales

2013-01-01

Full Text Available Nos últimos anos, o equino atleta vem sendo cada vez mais requerido. Dessa forma, as exigências por alto desempenho têm fomentado o interesse pelo estudo das afecções relacionadas com a fisiopatologia de diversas enfermidades dos equinos. A relação entre o íon magnésio e o exercício físico tem recebido atenção significativa visto que este íon está intimamente relacionado ao tecido muscular estriado esquelético. Além disso, dentre as principais estratégias para a detecção e acompanhamento clínico de lesões musculares, destacam-se a avaliação das atividades das enzimas creatino quinase (CK, lactato desidrogenase (LDH e aspartato aminotransferase (AST. A busca pelo estabelecimento de parâmetros que se relacionam entre si é um fator determinante na compreensão de alterações fisiológicas encontradas diante do esforço em equinos atletas. Desta forma, o presente trabalho teve como objetivo determinar como as concentrações sanguíneas do íon magnésio e as atividades enzimáticas das enzimas CK, LDH e AST comportaram-se em equinos Puro Sangue Árabe finalistas de provas de enduro de 90km e relacionar as possíveis alterações com o tipo de esforço físico desempenhado pelos animais. Foram avaliadas a atividade enzimática das enzimas CK, LDH, AST e a concentração do íon magnésio no exercício em relação ao repouso de 14 equinos clinicamente hígidos da raça Puro Sangue Árabe, sendo 9 machos e 5 fêmeas, com idades variando entre 6 a 12 anos, submetidos a treinamento para enduro e participantes de provas de 90 km. Pode-se observar que as variáveis acima mencionadas sofreram aumento com diferença estatística em relação ao repouso. O exercício físico de enduro determinou a ocorrência de alterações nas atividades enzimáticas das enzimas CK (p≤0,001, LDH (p=0,0001, AST (p=0,0007 e na concentração do íon magnésio (p=0,0004, no exercício em relação ao repouso (p≤0,05. Fato que determinou altera

Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy.

Science.gov (United States)

Theyer, G; Dürer, A; Theyer, U; Haberl, I; Ulsperger, E; Baumgartner, G; Hamilton, G

1999-10-01

The present study evaluated monthly measurements of free and total prostate-specific antigen (PSA), and the tumor proliferation markers tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFRA 21-1) in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Thirty-four men received alternating cycles of 8 month androgen suppression and treatment cessation (mean duration, 10.3 months) until PSA increased to >20 microg/l. Measurements of testosterone, percentage of free PSA, TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to IAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 months of androgen suppression treatment. During treatment cessation, TPS exceeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. PSA is the best and most sensitive marker of prostate cancer regression and regrowth during IAS cycles of the markers tested in this study. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in IAS seem to be related mainly to effects on normal androgen-dependent tissues. Copyright 1999 Wiley-Liss, Inc.

Investigation of the polyvinyl alcohol stabilization mechanism and adsorption properties on the surface of ternary mixed nanooxide AST 50 (Al{sub 2}O{sub 3}–SiO{sub 2}–TiO{sub 2})

Energy Technology Data Exchange (ETDEWEB)

Wiśniewska, Małgorzata; Ostolska, Iwona, E-mail: i-ostolska@wp.pl; Szewczuk-Karpisz, Katarzyna; Chibowski, Stanisław [Maria Curie-Sklodowska University, Department of Radiochemistry and Colloids Chemistry, Faculty of Chemistry (Poland); Terpiłowski, Konrad [Maria Curie-Sklodowska University, Department of Physical Chemistry – Interfacial Phenomena, Faculty of Chemistry (Poland); Gun’ko, Vladimir Moiseevich; Zarko, Vladimir Iljich [National Academy of Sciences in Ukraine, Institute of Surface Chemistry (Ukraine)

2015-01-15

A new adsorbent consisting of fumed, mixed alumina, silica, and titania in various proportions (AST 50) was investigated. The studied material was prepared by chemical vapor deposition method. The diameter of AST 50 primary particles was equal to about 51 nm which denotes that it can be classified as a nanomaterial. In the presented paper, the adsorption properties of polyvinyl alcohol on the ternary oxide were investigated. The polymer macromolecules were characterized by two different molecular weights and degree of hydrolysis. The polymer adsorption reaches the maximum at pH 3 and decreases with the solution pH rise. The reduction of the adsorbed PVA macromolecules is related to the electrostatic repulsion forces occurring in the studied system. The AST 50 point of zero charge (pH{sub pzc}) obtained from the potentiometric titration is equal to 4.7. Due to the nonionic character of the analyzed macromolecular compound, the polymer attendance has an insignificant effect on the AST 50 surface charge density. In the case of the adsorbent particles zeta potential, the obtained dependencies are different in the absence and presence of PVA. The shift of the slipping plane and displacement of the counter-ions from Stern layer by the adsorbed polymer chains have the greatest effect on the ζ potential value. The stability measurements indicate that the AST 50 suspensions in the presence of the background electrolyte at pH 3 and 6 are unstable. In turn, in an alkaline medium the mixed oxide suspensions exhibit the highest durability, which is a result of a large number of the negative charges on the AST 50 surface. The addition of PVA 100 significantly improves the suspension stability at pH 3 and 6; at higher pH value, the polymer presence does not influence the system durability. It is related to the steric and electrosteric stabilization of the colloidal particles by the adsorbed polyvinyl alcohol macromolecules.

USE OF SACCHROMYCES CERVISIAE TO SUPPRESS THE EFFECTS OF FUMONISIN MYCOTOXICOSIS IN JAPANESE QUAIL

International Nuclear Information System (INIS)

ABU TALEB, A.M.

2008-01-01

In this study, 400 unsexed Japanese quail chicks (1 day old) were used. The quail chicks were randomly assigned into four groups of 100 birds in each. The first group was served as control. The other experimental groups were fed on a basal diet supplemented with 0.5% yeast/kg diet (G2), 0.5% yeast/kg diet ± 200 mg fumonicin-B1/kg diet (G3) and 200 mg fumonicin-B1/kg diet (G4). The results showed significant increases in mortality rate, GPT (ALT), GOT (AST), cholesterol, uric acid, creatinine and alpha-fetoprotein (AFP) and decreases in body weight, hatchability, fertility and hatching weight, serum total proteins, globulin and glutathione peroxidase (GPx) activity in group of quails received fumonisin (G4) in comparison with the control group (G1) and all treatments. Yeast led to partial improvement in the parameters in group two (G2). Also, yeast suppressed the toxic effect of fumonisin B-1 (G3)

USE OF SACCHROMYCES CERVISIAE TO SUPPRESS THE EFFECTS OF FUMONISIN MYCOTOXICOSIS IN JAPANESE QUAIL

Energy Technology Data Exchange (ETDEWEB)

ABU TALEB, A M [Biological Applications Dept., Radioisotope Applications Division, Nuclear Research Center, Abou-Zaable, Inshas (Egypt)

2008-07-01

In this study, 400 unsexed Japanese quail chicks (1 day old) were used. The quail chicks were randomly assigned into four groups of 100 birds in each. The first group was served as control. The other experimental groups were fed on a basal diet supplemented with 0.5% yeast/kg diet (G2), 0.5% yeast/kg diet {+-} 200 mg fumonicin-B1/kg diet (G3) and 200 mg fumonicin-B1/kg diet (G4). The results showed significant increases in mortality rate, GPT (ALT), GOT (AST), cholesterol, uric acid, creatinine and alpha-fetoprotein (AFP) and decreases in body weight, hatchability, fertility and hatching weight, serum total proteins, globulin and glutathione peroxidase (GPx) activity in group of quails received fumonisin (G4) in comparison with the control group (G1) and all treatments. Yeast led to partial improvement in the parameters in group two (G2). Also, yeast suppressed the toxic effect of fumonisin B-1 (G3)

Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa.

Science.gov (United States)

Petersen, Maya; Balzer, Laura; Kwarsiima, Dalsone; Sang, Norton; Chamie, Gabriel; Ayieko, James; Kabami, Jane; Owaraganise, Asiphas; Liegler, Teri; Mwangwa, Florence; Kadede, Kevin; Jain, Vivek; Plenty, Albert; Brown, Lillian; Lavoy, Geoff; Schwab, Joshua; Black, Douglas; van der Laan, Mark; Bukusi, Elizabeth A; Cohen, Craig R; Clark, Tamara D; Charlebois, Edwin; Kamya, Moses; Havlir, Diane

2017-06-06

increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents). Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation. clinicaltrials.gov Identifier: NCT01864683.

PARÁMETROS BIOQUÍMICOS ENZIMÁTICOS (ALT, AST, ALP, Γ-GT, LDH EN NIÑOS CON LEUCEMIA LINFOBLÁSTICA AGUDA ANTES DEL TRATAMIENTO ANTINEOPLÁSICO

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Jeél Moya S

2015-12-01

Full Text Available Objective: To determine the enzymatic biochemical parameters (glutamic pyruvic transaminase (ALT, glutamic oxaloacetic transaminase (AST, alkaline phosphatase (ALP, gamma glutamyltransferase (γ-GT, and lactate dehydrogenase (LDH in children with acute lymphoblastic leukemia (ALL before cancer treatment. Material and Methods: A prospective experimental, observational, cross-sectional study was conducted in 30 children between 2 and 15 years old, from several Neoplastic Centers in Lima. Blood collection was performed in BD red cap Vacutainer tubes, processed in the semi-automated analyzer BIOTEC® EMP-168, with Wiener Lab Group enzyme reagents under the modified method Szaaz and UV-Optimized by IFCC, SSCC and SFBC. Finally, coding and tabulation was performed. Results: 60% were boys and 46.7% are between the ages of 2-6 years. Serum levels of AST were increased by 33.3% in boys and 50% in girls. Serum ALT values were increased in 33.3% of boys and 41.7% of girls; only 25% of girls showed increased levels of γ-GT values; ALP was increased in 44.4% of boys and 66.7% of girls. Moreover LDH levels were increased in 55.6% of boys and 41.7% of girls. Conclusions: The enzymatic tests LDH, AST, ALT and ALP are increased in children with ALL compared to normal values due to tumor lysis syndrome characterized by electrolyte abnormalities, and as a result of the massive destruction of tumor cells and rapid release of large amounts of intracellular elements.

Theoretical model for investigating the dynamic behaviour of the AST-500 type nuclear heating station reactor

International Nuclear Information System (INIS)

Grundmann, U.; Rohde, U.; Naumann, B.

1985-01-01

Studies on theoretical simulation of the dynamic behaviour of the AST-500 type reactor primary coolant system are summarized. The first version of a dynamic model in the form of the DYNAST code is described. The DYNAST code is based on a one-dimensional description of the primary coolant circuit including core, draught stack, and intermediate heat exchanger, a vapour dome model, and the point model of neutron kinetics. With the aid of the steady-state computational part of the DYNAST code, studies have been performed on different steady-state operating conditions. Furthermore, some methodological investigations on generalization and improvement of the dynamic model are considered and results presented. (author)

Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

International Nuclear Information System (INIS)

Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

2008-01-01

Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

Pharmacologic suppression of target cell recognition by engineered T cells expressing chimeric T-cell receptors.

Science.gov (United States)

Alvarez-Vallina, L; Yañez, R; Blanco, B; Gil, M; Russell, S J

2000-04-01

Adoptive therapy with autologous T cells expressing chimeric T-cell receptors (chTCRs) is of potential interest for the treatment of malignancy. To limit possible T-cell-mediated damage to normal tissues that weakly express the targeted tumor antigen (Ag), we have tested a strategy for the suppression of target cell recognition by engineered T cells. Jurkat T cells were transduced with an anti-hapten chTCR tinder the control of a tetracycline-suppressible promoter and were shown to respond to Ag-positive (hapten-coated) but not to Ag-negative target cells. The engineered T cells were then reacted with hapten-coated target cells at different effector to target cell ratios before and after exposure to tetracycline. When the engineered T cells were treated with tetracycline, expression of the chTCR was greatly decreased and recognition of the hapten-coated target cells was completely suppressed. Tetracycline-mediated suppression of target cell recognition by engineered T cells may be a useful strategy to limit the toxicity of the approach to cancer gene therapy.

Suppression of human breast tumors in NOD/SCID mice by CD44 shRNA gene therapy combined with doxorubicin treatment

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Pham PV

2012-05-01

Full Text Available Phuc Van Pham1, Ngoc Bich Vu1, Thuy Thanh Duong1, Tam Thanh Nguyen1, Nhung Hai Truong1, Nhan Lu Chinh Phan1, Tue Gia Vuong1, Viet Quoc Pham1, Hoang Minh Nguyen1, Kha The Nguyen1, Nhung Thi Nguyen1, Khue Gia Nguyen1, Lam Tan Khat1, Dong Van Le2, Kiet Dinh Truong1, Ngoc Kim Phan11Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, HCM City, 2Military Medical University, Ha Noi, VietnamBackground: Breast cancer stem cells with a CD44+CD24- phenotype are the origin of breast tumors. Strong CD44 expression in this population indicates its important role in maintaining the stem cell phenotype. Previous studies show that CD44 down-regulation causes CD44+CD24- breast cancer stem cells to differentiate into non-stem cells that are sensitive to antitumor drugs and lose many characteristics of the original cells. In this study, we determined tumor suppression in non-obese severe combined immunodeficiency mice using CD44 shRNA therapy combined with doxorubicin treatment.Methods: Tumor-bearing non-obese severe combined immunodeficiency mice were established by injection of CD44+CD24- cells. To track CD44+CD24- cells, green fluorescence protein was stably transduced using a lentiviral vector prior to injection into mice. The amount of CD44 shRNA lentiviral vector used for transduction was based on CD44 down-regulation by in vitro CD44 shRNA transduction. Mice were treated with direct injection of CD44 shRNA lentiviral vector into tumors followed by doxorubicin administration after 48 hours. The effect was evaluated by changes in the size and weight of tumors compared with that of the control.Results: The combination of CD44 down-regulation and doxorubicin strongly suppressed tumor growth with significant differences in tumor sizes and weights compared with that of CD44 down-regulation or doxorubicin treatment alone. In the combination of CD44 down-regulation and doxorubicin group, the tumor weight was

Role of fluconazole in the long-term suppressive therapy of fungal infections in patients with artificial implants.

Science.gov (United States)

Penk, A; Pittrow, L

1999-12-01

With the increased use of artificial implants the management of related infections has become an important challenge. Normally an infected implant would be removed. In many cases this might be contraindicated and drug treatment remains as the only alternative. As microbiological eradication is often impossible, especially in fungal infections at artificial implants (FIAI) long-term suppressive therapy might be required. The objective of this study was to determine the therapeutic value of fluconazole (F) in the management of FIAI. Clinical data of 56 patients (pts) with proven or suspected fungal infections and artificial implants (FIAI) subsequently treated with F were analyzed retrospectively. FIAI caused by species with intrinsic resistance to F have been excluded from the study. The following implants were involved: prosthetic valve endocarditis (PVE) 25 pts (44.6%), intraocular lenses (IL) 9 pts (16.1%), ventriculoperitoneal shunts (VPS) 6 pts (10.7%), knee prostheses (KP) 5 pts (8.9%), biliary stents (BS) 4 pts (7.1 %), venous access devices (VAS) 3 pts (5.4%), urinary stents (US) 2 pts (3.6%), breast implant and pacemaker 1 patient (1.8%) each. Underlying diseases were valve insufficiency (in PVE), cataract surgery (in IL), prematurity in newborns (in VPS), arthrosis (in KP), biliary obstruction (in BS), cystic fibrosis (in VAS), and obstructive renal calculi (in US). Candida species (C. spp.) were the most frequently detected causative agents with C. parapsilosis as the leading cause (n = 19; 33.9%). Furthermore C. albicans (n = 15; 26.8%), C. spp. and fungi not further specified (n = 8; 14.3%), C. tropicalis (n = 3; 5.4%), C. glabrata (n = 3; 5.4%), and C. lusitaniae (n = 1; 1.8%) were identified. Acremonium kiliense has been detected in 4 pts (7.1%), Cryptococcus neoformans in 2 pts (3.6 %). Histoplasma capsulatum was identified in 1 patient (1.8%). The maximum duration of treatment with F was lifelong with a maximum recorded duration of 4,5 years. The

Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

Science.gov (United States)

Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

2010-01-01

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

Effect of chronic L-thyroxine-suppressive therapy on cardiac function in patients with differentiated thyroid carcinoma: Radionuclide techniques

International Nuclear Information System (INIS)

Ziada, G.; Farouk, S.; Zidan, A.; Mustafa, S.; El-Reffaie, S.

2005-01-01

Differentiated thyroid carcinoma (DTC) is usually treated by a combination of surgery, radioiodine (I-131) and suppressive doses of thyroid hormones [L-thyroxine (Eltroxine)]. It is well-known that thyroid hormone affects the function of cardiovascular system. However there is no study to objectively substantiate this phenomenon. The objective of this study was to assess the left ventricular function with the help of radionuclide ventriculography in patients of DTC. Various parameters of systolic function [ejection fraction (EF), peak ejection rate (PER) and time to peak ejection rate (TPER)], diastolic function [peak filling rate (PFR) and time to peak filling rate (TPFR)] and heart rate were determined. Ten healthy control subjects and 50 patients of DTC on suppressive doses of eltroxine following surgery and radio-iodine (I-131) therapy were evaluated. The patients were divided into 5 groups according to their clinical status and thyroid hormone profile. These groups were: euthyroid, sub-clinical hypothyroid, hypothyroid, sub-clinical hyperthyroid and hyperthyroid groups. The results of the study revealed that Eltroxine significantly affected left ventricular function. Although it did not affect the systolic function, the diastolic function was significantly impaired. Prolongation of TPER was noted in hypothyroid patients, while the same was significantly decreased in hyper- and sub-clinical hyper-thyroids patients. Such abnormalities in cardiac function would be responsible for serious morbidity and could affect the lives of patients' in several ways. Hence, early effective treatment of thyroid function is important in patients of DTC, which would improve their quality of life and avoid long-term serious or irreversible cardiovascular disorder. (author)

Dupuytren’s and Ledderhose Diseases in a Family with LMNA-Related Cardiomyopathy and a Novel Variant in the ASTE1 Gene

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Michael V. Zaragoza

2017-11-01

Full Text Available Dupuytren’s disease (palmar fibromatosis involves nodules in fascia of the hand that leads to flexion contractures. Ledderhose disease (plantar fibromatosis is similar with nodules of the foot. While clinical aspects are well-described, genetic mechanisms are unknown. We report a family with cardiac disease due to a heterozygous LMNA mutation (c.736C>T, p.Gln246Stop with palmar/plantar fibromatosis and investigate the hypothesis that a second rare DNA variant increases the risk for fibrotic disease in LMNA mutation carriers. The proband and six family members were evaluated for the cardiac and hand/feet phenotypes and tested for the LMNA mutation. Fibroblast RNA studies revealed monoallelic expression of the normal LMNA allele and reduced lamin A/C mRNAs consistent with LMNA haploinsufficiency. A novel, heterozygous missense variant (c.230T>C, p.Val77Ala in the Asteroid Homolog 1 (ASTE1 gene was identified as a potential risk factor in fibrotic disease using exome sequencing and family studies of five family members: four LMNA mutation carriers with fibromatosis and one individual without the LMNA mutation and no fibromatosis. With a possible role in epidermal growth factor receptor signaling, ASTE1 may contribute to the increased risk for palmar/plantar fibromatosis in patients with Lamin A/C haploinsufficiency.

Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.

Science.gov (United States)

Andersen-Nissen, Erica; Chang, Joanne T; Thomas, Katherine K; Adams, Devin; Celum, Connie; Sanchez, Jorge; Coombs, Robert W; McElrath, M Juliana; Baeten, Jared M

2016-12-01

Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment. To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines. Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment. These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.

DETERMINAÇÃO DOS VALORES MÉDIOS DAS ENZIMAS AST, DHL, gGT E FAS NO SORO DE EQUINOS SADIOS EM SANTA MARIA, RS

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Sônia Terezinha dos Anjos Lopes

1993-12-01

Full Text Available Foram usados 50 eqüinos sadios provenientes do Batalhão de Polícia Montada da Brigada Militar em Santa Maria, RS, sendo 43 machos e 7 fêmeas com idade variadas a partir de 3 anos. Foram colhidos 10ml de sangue da jugular para determinação dos valores da atividade sérica das enzimas aspartato-aminotransferase (AST, desidrogenase lática (DHL, gama-glutamiltransferase (gGT e fosfatase alcalina sérica (FAS. Os resultados encontrados para AST foi de 101 - 190U/I com média de 130UI; DHL foi de 100 - 421 U/l com média de 182U/I; gGT foi de 2 - 27U/I com média de 6.5U/I e FAS foi de 103 - 335U/I com média de 190U/I. A partir de outubro/1992 estes valores passaram a ser referência no laboratório de Patologia Clínica do Hospital de Clinicas Veterinárias da Universidade Federal de Santa Maria.

Evidence for the Standard Model Higgs boson in the WW$^{\\ast}$ decay mode using the data collected by the ATLAS detector at the LHC

CERN Document Server

Jovicevic, Jelena; Strandberg, Jonas

2015-11-20

The $H \\rightarrow WW^{\\ast}$ channel was one of the three search channels contributing in the observation of the Higgs boson at the ATLAS experiment in July 2012. Nowadays, this channel represents an important ingredient in the determination of the couplings and properties of the newly discovered particle. This thesis reports the search for and observation of the Higgs boson in the $H \\rightarrow WW^{\\ast}$ decay mode using the ATLAS detector at the CERN Large Hadron Collider. The analysis of events in which the Higgs boson is produced in the gluon-gluon fusion process and is associated with no more than one jet, is outlined in detail. The datasets used are the proton-proton collisions collected with the ATLAS detector at a centre of mass energy of 8 TeV during 2012 and 7 TeV during 2011, corresponding to a total integrated luminosity of 25 fb$^{-1}$. An excess over the predicted number of background events is observed in the data. The significance of the excess is estimated to be 6.1 standard deviations, ...

High level of viral suppression and low switch rate to second-line antiretroviral therapy among HIV-infected adult patients followed over five years: retrospective analysis of the DART trial.

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Cissy Kityo

Full Text Available In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM versus routine laboratory (CD4/haematology/biochemistry and clinical monitoring (LCM in HIV-infected adults initiating therapy. There was no virological monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two thousand three hundred and seventeen (2317 participants from this country initiated antiretroviral therapy with zidovudine/lamivudine plus tenofovir (n = 1717, abacavir (n = 300, or nevirapine (n = 300. Of 1896 (81.8% participants who were alive and in follow-up at trial closure (median 5.1 years after therapy initiation, 1507 (79.5% were on first-line and 389 (20.5% on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the rate was substantially higher in participants with low baseline CD4 counts (<50 cells/mm3. Among 1207 (80.1% first-line participants with viral load measured, HIV RNA was <400 copies/ml in 963 (79.8%, 400-999 copies/ml in 37 (3.1%, 1,000-9,999 copies/ml in 110 (9.1%, and ≥10,000 copies/ml in 97 (8.0%. The proportion with HIV RNA <400 copies/ml was slightly lower (difference 7.1%, 95% CI 2.5 to 11.5% in CDM (76.3% than in LCM (83.4%. Among 252 (64.8% second-line participants with viral load measured (median 2.3 years after switch, HIV RNA was <400 copies/ml in 226 (89.7%, with no difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable without viral load or CD4 count monitoring in the context of high-quality clinical care.ISRCTN13968779.

THERAPY DEVELOPMENTS IN SOUTHERN AFRICA

African Journals Online (AJOL)

the potential benefits of structured treatment interruptions. Second, extensive .... suppression can facilitate restoration of CD4+ T-cell prolif- erative responses to recall ..... women after initiation of protease inhibitor therapy. In: 12th World.

Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial.

Science.gov (United States)

Pulido, Federico; Ribera, Esteban; Lagarde, María; Pérez-Valero, Ignacio; Palacios, Rosario; Iribarren, José A; Payeras, Antoni; Domingo, Pere; Sanz, José; Cervero, Miguel; Curran, Adrián; Rodríguez-Gómez, Francisco J; Téllez, María J; Ryan, Pablo; Barrufet, Pilar; Knobel, Hernando; Rivero, Antonio; Alejos, Belén; Yllescas, María; Arribas, José R

2017-11-29

Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively. Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. NCT02159599. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Korean red ginseng and its primary ginsenosides inhibit ethanol-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells.

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Park, Hye-Min; Kim, Shang-Jin; Mun, A-Reum; Go, Hyeon-Kyu; Kim, Gi-Beum; Kim, Sung-Zoo; Jang, Seon-Il; Lee, Sei-Jin; Kim, Jin-Shang; Kang, Hyung-Sub

2012-06-14

Panax ginseng (P. ginseng) is one of the most widely used medicinal plants due to its wide spectrum of medicinal effects. Among the currently available Panax ginseng products, Korea red ginseng (KRG) has been shown to exhibit a variety of antioxidative and hepatoprotective action. Our aim was to investigate the effects of KRG and its primary ginsenosides (Rg3 and Rh2) on EtOH-induced injury to mouse hepatocytes (TIB-73). We investigated the effects of KRG and its primary ginsenoside on EtOH-induced injury to TIB-73 cells and evaluated MAPKs signals as a possible mechanism of action. Hepatocytic injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), ROS and mitochondria membrane potential (MMP) level in TIB-73 cells. The levels of MAPK activation were analyzed by Western blots. The results showed that exposure of EtOH to TIB-73 cells led to cell death and membrane damage, accompanied by a decrease in cell viability, MMP, and Mg(2+) concentrations, but an increase in LDH, AST, ROS and MAPK activation. KRG and its primary ginsenosides reduced EtOH-induced generation of ROS and the activation of ERK and JNK, and increased Mg(2+) concentrations. These results suggest that KRG and its primary ginsenosides inhibit EtOH-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2012-01-01

Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2015-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2017-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Pacing for the Suppression of Paroxysmal Atrial Fibrillation in an 87-year-old Patient

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Adel El-Bialy

2003-04-01

Full Text Available Background: Sinus node dysfunction, atrioventricular (AV block and atrial fibrillation (AF are associated with advanced age. Required therapy commonly includes pacemaker implantation. Methods: We report the course of therapy for an 87-year-old with symptomatic sinus node dysfunction and paroxysmal atrial fibrillation who was intolerant of drug therapy. Results: The patient received a pacemaker for treatment of sick sinus syndrome. She continued to have symptomatic episodes of AF and was intolerant of pharmacologic therapy despite adequate rate support provided by the pacemaker. The AF suppression algorithm in the pacemaker was enabled, resulting in the elimination all AF episodes effectively eliminating the need for antiarrhythmic medication. If this continues to stabilize her atrium, withdrawal of anticoagulation therapy is anticipated. Conclusions: The clinical presentation of sinus node dysfunction and related conduction abnormalities is common in the elderly. Pharmacologic management is often a challenge in the presence of the advanced age and concomitant disease processes. In individuals who have paroxysmal atrial fibrillation or are likely to develop this and who need a pacemaker for standard indications, the availability of an AF Suppression™ algorithm may facilitate their management without needed to use medications or being able to utilize lower doses of those medications.

Oral cyclosporine therapy for refractory severe vernal keratoconjunctivitis

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Nikhil S Gokhale

2012-01-01

Full Text Available We report the success of oral cyclosporine therapy in a patient with severe vision-threatening vernal keratoconjunctivitis. A child presented with severe allergy which was not controlled with topical steroids, cyclosporine and mast cell stabilizers. Oral steroids were required repeatedly to suppress inflammation. Child showed a dramatic improvement and stabilization with oral cyclosporine therapy. Oral cyclosporine therapy can be tried in severe vision-threatening allergy refractory to conventional therapy.

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

Science.gov (United States)

Alhagamhmad, Moftah H; Lemberg, Daniel A; Day, Andrew S; Tan, Li-Zsa; Ooi, Chee Y; Krishnan, Usha; Gupta, Nitin; Munday, John S; Leach, Steven T

2017-04-01

Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies. Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Behaviour of hormone parameters and equivalent iodide clearance (TcTu) on suppressive T4 treatment of enthyroid struma

International Nuclear Information System (INIS)

Greis, W.

1978-01-01

84 patients with euthyroid diffuse struma were stabilised at the individually necessary thyroxine dose by means of TcTU, T 4 , and NTR. As long-term medication, 100μg l-thyroxin were required in 143% of the patients, 150 μg in 83.3% of the patients, and 200 μg in 2.4% of the patients. After 8 to 12 weeks of therapy, the TcTU as an estimate of the iodide clearance was suppressed to 0.1 to 3.5 ( x +- s). T 4 and NTR values were near the upper limit of the normal at a normal T 3 level. After administration of 150 μg thyroxine per day for 12 weeks and 200μg thyroxine for 4 weeks, TcTU is suppressed to a comparable extent while the weaker suppressive effect of a 12 weeks' medication with 100μg thyroxine could not be improved even by a prolonged therapy. After one year of treatment, calculations of the thyroid surface in scintiscans showed a successful therapy in 82% of the patients while the circumference of the neck had become smaller only in 60% of the patients. Therapy was generally less successful in patients over 18 years of age. (orig.) [de

Suppressing effects of glucan on micronuclei induced by Co60 in mice

International Nuclear Information System (INIS)

Chorvatovicova, D.

1991-01-01

The effects of glucan on the frequency of micronuclei in polychromatic erythrocytes of A/Ph mouse bone marrow induced by Co 60 irradiation were examined. Suppressing effect of three glucan derivatives was statistically significant (P 3 substituent (DS 0.89). Intraperitoneal application of glucan has to be done earlier than one hour after irradiation. The suppressive effects of glucans can be explained by their ability to trap OH radicals and so decrease the clastogenic effect of irradiation. The results may be useful for therapeutic application of glucan with radiation therapy. (orig.) [de

Topotactic conversion of β-helix-layered silicate into AST-type zeolite through successive interlayer modifications.

Science.gov (United States)

Asakura, Yusuke; Takayama, Ryosuke; Shibue, Toshimichi; Kuroda, Kazuyuki

2014-02-10

AST-type zeolite with a plate morphology can be synthesized by topotactic conversion of a layered silicate (β-helix-layered silicate; HLS) by using N,N-dimethylpropionamide (DPA) to control the layer stacking of silicate layers and the subsequent interlayer condensation. Treatment of HLS twice with 1) hydrochloric acid/ethanol and 2) dimethylsulfoxide (DMSO) are needed to remove interlayer hydrated Na ions and tetramethylammonium (TMA) ions in intralayer cup-like cavities (intracavity TMA ions), both of which are introduced during the preparation of HLS. The utilization of an amide molecule is effective for the control of the stacking sequence of silicate layers. This method could be applicable to various layered silicates that cannot be topotactically converted into three-dimensional networks by simple interlayer condensation by judicious choice of amide molecules. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

10 Hz Amplitude Modulated Sounds Induce Short-Term Tinnitus Suppression

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Patrick Neff

2017-05-01

Full Text Available Objectives: Acoustic stimulation or sound therapy is proposed as a main treatment option for chronic subjective tinnitus. To further probe the field of acoustic stimulations for tinnitus therapy, this exploratory study compared 10 Hz amplitude modulated (AM sounds (two pure tones, noise, music, and frequency modulated (FM sounds and unmodulated sounds (pure tone, noise regarding their temporary suppression of tinnitus loudness. First, it was hypothesized that modulated sounds elicit larger temporary loudness suppression (residual inhibition than unmodulated sounds. Second, with manipulation of stimulus loudness and duration of the modulated sounds weaker or stronger effects of loudness suppression were expected, respectively.Methods: We recruited 29 participants with chronic tonal tinnitus from the multidisciplinary Tinnitus Clinic of the University of Regensburg. Participants underwent audiometric, psychometric and tinnitus pitch matching assessments followed by an acoustic stimulation experiment with a tinnitus loudness growth paradigm. In a first block participants were stimulated with all of the sounds for 3 min each and rated their subjective tinnitus loudness to the pre-stimulus loudness every 30 s after stimulus offset. The same procedure was deployed in the second block with the pure tone AM stimuli matched to the tinnitus frequency, manipulated in length (6 min, and loudness (reduced by 30 dB and linear fade out. Repeated measures mixed model analyses of variance (ANOVA were calculated to assess differences in loudness growth between the stimuli for each block separately.Results: First, we found that all sounds elicit a short-term suppression of tinnitus loudness (seconds to minutes with strongest suppression right after stimulus offset [F(6, 1331 = 3.74, p < 0.01]. Second, similar to previous findings we found that AM sounds near the tinnitus frequency produce significantly stronger tinnitus loudness suppression than noise [vs. Pink

Myopathy Associated with Acute Hypothyroidism following Radioiodine Therapy for Graves Disease in an Adolescent

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Rivkees ScottA

2010-08-01

Full Text Available We describe acute myopathy following I-131 treatment for hyperthyroidism due to Graves Disease (GD in an adolescent. A 15 year-old diagnosed with GD required treatment with radioactive iodine (I-131 therapy. Six weeks post I-131, he developed generalized muscle cramps. The CK was 19.800 U/L, the total thyroxine was 2.3 mcg/dL (29.6 nmol/L SI and the estimated free thyroxine (EFT was 0.5 ng/dL (6.4 pmol/L SI. The ALT was 112 U/L and AST was 364 U/L (normal

Adaptive therapy.

Science.gov (United States)

Gatenby, Robert A; Silva, Ariosto S; Gillies, Robert J; Frieden, B Roy

2009-06-01

A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol. Here we examine an adaptive therapeutic approach that evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype as well as therapy-induced perturbations. Initial mathematical models find that when resistant phenotypes arise in the untreated tumor, they are typically present in small numbers because they are less fit than the sensitive population. This reflects the "cost" of phenotypic resistance such as additional substrate and energy used to up-regulate xenobiotic metabolism, and therefore not available for proliferation, or the growth inhibitory nature of environments (i.e., ischemia or hypoxia) that confer resistance on phenotypically sensitive cells. Thus, in the Darwinian environment of a cancer, the fitter chemosensitive cells will ordinarily proliferate at the expense of the less fit chemoresistant cells. The models show that, if resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations. We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant

Effectiveness of Dry Cow Therapy Comprising Antibiotic Treatment, Internal Teat Sealant, and α-Tocopherol Against New Intramammary Infections in Cows

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Cengiz Mehmet

2015-04-01

Full Text Available The aim of this study was to evaluate the preventive effectiveness of dry cow therapy based on antibiotic, internal teat sealant, and α-tocopherol administered separately or in various combinations at drying-off The study was performed on 322 uninfected quarters of 95 cows originating from three dairy herds. The new intramammary infection rates after calving were measured to evaluate the effectiveness. The quarters were divided into six groups differing in treatment, namely: control group (group C, n = 40 and five treatment groups. Treatment groups were arranged as follows: group A (antibiotic alone, n = 81, group AS (antibiotic + sealant, n = 40, group AST (antibiotic + sealant + α-tocopherol, n = 40, group T (α-tocopherol alone, n = 40, group S (sealant alone, n = 81. New infection rate amounted to 47.5% in group C. The treatment in group AST significantly prevented from the occurrence of new intramammary infections (12.5%, P 0.05, although the use of the sealant alone (group S decreased the risk of new infection (24.7%, P 0.05. Increased α-tocopherol level (P < 0.05 was detected after calving in the quarters from cows that received α-tocopherol injections. In conclusion, the combination of antibiotic, internal teat sealant, and α-tocopherol used in dry cow therapy showed a significantly better preventive effect against new intramammary infections, than the therapeutics administered separately.

Activity of Catalase (CAT, ALT and AST in Different Organs of Swiss Albino Mice Treated with Lead Acetate, Vitamin C and Magnesium-L-Threonate

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Ilir Nazmi Mazreku

2017-11-01

Full Text Available Introduction: Lead is a natural element with toxic properties and is widespread in the environment. Lead toxicity is associated with generation of reactive oxygen and nitrogen species and consumption of antioxidants elements (vitamin E and C, glutathione, thioredoxin and lipoic acid, melatonin, carotenoids and natural flavonoids in the cell, and unbalancing oxidantsantioxidants levels. Aim: To evaluate the effects of different chemical combinations (lead acetate, Vitamin C and Magnesium-L-threonate on antioxidant enzyme activity (catalase-CAT of liver, kidney, spleen, pancreas and brain, and serum transaminases [Serum Alanine Transaminase (ALT and Serum Aspartate Transaminase (AST]. Materials and Methods: Experimental animals (49 male Mus musculus-swiss albino mice were separated into five different groups. The first group was used as a control, hence the other four groups were treated with sub-lethal doses (90 mg/kg of lead acetate (group 2, lead acetate (90 mg/kg and Vitamin C dose 40mg/kg (group 3, lead acetate (90 mg/kg and Magnesium-Lthreonate dose 100 mg/kg (group 4 and only with MagnesiumL-threonate dose 100 mg/kg (group 5, during the treatment period (40 days. Blood samples were taken from the facial vein and used for transaminase analysis. Organ tissue was collected after euthanizing anaesthetized animals with neck dislocation technique. Results: The results showed that lead acetate treatment has caused significant elevation in the activity of AST (group 2 and 3 and ALT (group 3. Also, CAT activity was significantly (p<0.05 increased in groups treated with lead acetate (liver, pancreas, kidney and brain but not in spleen. Treatment of lead intoxicated groups with Vitamin C and Magnesium L-threonate increased significantly CAT activity in brain. Conclusion: Lead effects by interacting with different molecular systems and increasing enzyme activity (CAT, ALT and AST. Effects on CAT activity of Magnesium-L-threonate and Vitamin C treatment

Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer.

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Pujol, P; Daures, J P; Nsakala, N; Baldet, L; Bringer, J; Jaffiol, C

1996-12-01

We investigate whether the prognosis of patients with differentiated thyroid cancer is improved by maintaining a greater level of TSH suppression. One hundred and forty-one patients who underwent hormone therapy after thyroidectomy were followed up from 1970 to 1993 (mean, 95 months). Patients received levothyroxine (L-T4; mean dose, 2.6 micrograms/kg-day). TSH suppression was evaluated by TRH stimulation test until 1986 and thereafter by a second generation immunoradiometric assay. As TSH underwent fluctuation over time in most patients, we focused on subgroups of patients with relatively constant TSH levels during the follow-up. The relapse-free survival (RFS) was longer in the group with constantly suppressed TSH (all TSH values, or = 1 mU/L; n = 15; P 90% of undetectable TSH values; n = 19) had a trend toward a longer RFS than the remaining population (n = 102; P = 0.14). The patients with a lesser degree of TSH suppression (< 10% of undetectable TSH values; n = 27) had a shorter RFS than the remaining patients (n = 94; P < 0.01). In multivariate analysis that included TSH suppression, age, sex, histology, and tumor node metastasis stage, the degree of TSH suppression predicted RFS independently of other factors (P = 0.02). This study shows that a lesser degree of TSH suppression is associated with an increased incidence of relapse, supporting the hypothesis that a high level of TSH suppression is required for the endocrine management of thyroid cancer.

Reward enhances tic suppression in children within months of tic disorder onset

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Deanna J. Greene

2015-02-01

Full Text Available Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic.

REWARD ENHANCES TIC SUPPRESSION IN CHILDREN WITHIN MONTHS OF TIC DISORDER ONSET

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Greene, Deanna J.; Koller, Jonathan M.; Robichaux-Viehoever, Amy; Bihun, Emily C.; Schlaggar, Bradley L.; Black, Kevin J.

2014-01-01

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic. PMID:25220075

Observation and measurement of Higgs boson decays to $WW^\\ast$ with the ATLAS detector

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Aad, Georges; Abdallah, Jalal; Abdel Khalek, Samah; Abdinov, Ovsat; Aben, Rosemarie; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Allbrooke, Benedict; Allison, Lee John; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Anduaga, Xabier; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Auerbach, Benjamin; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Axen, Bradley; Azuelos, Georges; Azuma, Yuya; Baak, Max; Baas, Alessandra; Bacci, Cesare; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Badescu, Elisabeta; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Bain, Travis; Baines, John; Baker, Oliver Keith; Balek, Petr; Balli, Fabrice; Banas, Elzbieta; Banerjee, Swagato; Bannoura, Arwa A E; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Bartsch, Valeria; Bassalat, Ahmed; Basye, Austin; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Battistin, Michele; Bauer, Florian; Bawa, Harinder Singh; Beacham, James Baker; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Anne Kathrin; Becker, Sebastian; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bedikian, Sourpouhi; Bednyakov, Vadim; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Behr, Katharina; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Bensinger, James; Bentvelsen, Stan; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Beringer, Jürg; Bernard, Clare; Bernard, Nathan Rogers; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertolucci, Federico; Bertsche, Carolyn; Bertsche, David; Besana, Maria Ilaria; Besjes, Geert-Jan; Bessidskaia, Olga; Bessner, Martin Florian; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bevan, Adrian John; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Bierwagen, Katharina; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boddy, Christopher Richard; Boehler, Michael; Boek, Thorsten Tobias; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bogouch, Andrei; Bohm, Christian; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Boldyrev, Alexey; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boterenbrood, Hendrik; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boutouil, Sara; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozic, Ivan; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brelier, Bertrand; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Richard; Bressler, Shikma; Bristow, Kieran; Bristow, Timothy Michael; Britton, Dave; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Brown, Jonathan; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Brunet, Sylvie; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Bucci, Francesca; Buchholz, Peter; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Buehrer, Felix; Bugge, Lars; Bugge, Magnar Kopangen; Bulekov, Oleg; Bundock, Aaron Colin; Burckhart, Helfried; Burdin, Sergey; Burghgrave, Blake; Burke, Stephen; Burmeister, Ingo; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Buszello, Claus-Peter; Butler, Bart; Butler, John; Butt, Aatif Imtiaz; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Byszewski, Marcin; Cabrera Urbán, Susana; Caforio, Davide; Cakir, Orhan; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Caloba, Luiz; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarda, Stefano; Cameron, David; Caminada, Lea Michaela; Caminal Armadans, Roger; Campana, Simone; Campanelli, Mario; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cano Bret, Marc; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Cattani, Giordano; Caudron, Julien; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerio, Benjamin; Cerny, Karel; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chang, Philip; Chapleau, Bertrand; Chapman, John Derek; Charfeddine, Driss; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Chiefari, Giovanni; Childers, John Taylor; Chilingarov, Alexandre; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Chouridou, Sofia; Chow, Bonnie Kar Bo; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Ciftci, Rena; Cinca, Diane; Cindro, Vladimir; Ciocio, Alessandra; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clemens, Jean-Claude; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cooper-Smith, Neil; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Daniells, Andrew Christopher; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davignon, Olivier; Davison, Adam; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Doglioni, Caterina; Doherty, Tom; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Dris, Manolis; Dubbert, Jörg; Dube, Sourabh; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudziak, Fanny; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dwuznik, Michal; Dyndal, Mateusz; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Engelmann, Roderich; Erdmann, Johannes; Ereditato, Antonio; Eriksson, Daniel; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrag, Samir; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Julia; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franconi, Laura; Franklin, Melissa; Fraternali, Marco; French, Sky; Friedrich, Conrad; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gellerstedt, Karl; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gianotti, Fabiola; Gibbard, Bruce; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Glonti, George; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Grebenyuk, Oleg; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Guan, Liang; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guicheney, Christophe; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Gupta, Shaun; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guttman, Nir; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Hall, David; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Makoto; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Hejbal, Jiri; Helary, Louis; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hinman, Rachel Reisner; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hoffmann, Dirk; Hohlfeld, Marc; Holmes, Tova Ray; Hong, Tae Min; Hooft van Huysduynen, Loek; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Hurwitz, Martina; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Ilchenko, Iurii; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivarsson, Jenny; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jejelava, Juansher; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kalderon, Charles William; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karamaoun, Andrew; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Keyes, Robert; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharlamov, Alexey; Khodinov, Alexander; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Klok, Peter; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Koll, James; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laier, Heiko; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Hurng-Chun; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzen, Georg; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Lester, Christopher Michael; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Bo; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Shu; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan; Long, Robin Eamonn; Looper, Kristina Anne; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lungwitz, Matthias; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeno, Mayuko; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Mahmoud, Sara; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mantoani, Matteo; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marjanovic, Marija; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Homero; Martinez, Mario; Martin-Haugh, Stewart; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazza, Simone Michele; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Mechnich, Joerg; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Meric, Nicolas; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Migas, Sylwia; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Mori, Daniel; Morii, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morton, Alexander; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Thibaut; Muenstermann, Daniel; Mullen, Paul; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Nanava, Gizo; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negri, Guido; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nomachi, Masaharu; Nomidis, Ioannis; Norberg, Scarlet; Nordberg, Markus; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Palka, Marek; 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2015-07-16

We report the observation of Higgs boson decays to $WW^{\\ast}$ based on an excess over background of 6.1 standard deviations in the dilepton final state, where the Standard Model expectation is 5.8 standard deviations. Evidence for the vector-boson fusion (VBF) production process is obtained with a significance of 3.2 standard deviations. The results are obtained from a data sample corresponding to an integrated luminosity of $25~\\textrm{pb}^{-1}$ from $\\sqrt{s}=7$ and 8 TeV $pp$ collisions recorded by the ATLAS detector at the LHC. For a Higgs boson mass of 125.36 GeV, the ratio of the measured value to the expected value of the total production cross section times branching fraction is $1.09^{+0.16}_{-0.15}~\\textrm{(stat.)}^{+0.17}_{-0.14}~\\textrm{(syst.)}$. The corresponding ratios for the gluon fusion and vector-boson fusion production mechanisms are $1.02\\pm 0.19~\\textrm{(stat.)}^{+0.22}_{-0.18}~\\textrm{(syst.)}$ and $1.27^{+0.44}_{-0.40}~\\textrm{(stat.)}^{+0.30}_{-0.21}~\\textrm{(syst.)}$, respectively. ...

Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

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Binhua Ling

Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

Innate immune reconstitution with suppression of HIV-1.

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Scully, Eileen P; Lockhart, Ainsley; Garcia-Beltran, Wilfredo; Palmer, Christine D; Musante, Chelsey; Rosenberg, Eric; Allen, Todd M; Chang, J Judy; Bosch, Ronald J; Altfeld, Marcus

2016-03-17

Progressive HIV-1 infection leads to both profound immune suppression and pathologic inflammation in the majority of infected individuals. While adaptive immune dysfunction, as evidenced by CD4 + T cell depletion and exhaustion, has been extensively studied, less is known about the functional capacity of innate immune cell populations in the context of HIV-1 infection. Given the broad susceptibility to opportunistic infections and the dysregulated inflammation observed in progressive disease, we hypothesized that there would be significant changes in the innate cellular responses. Using a cohort of patients with multiple samplings before and after antiretroviral therapy (ART) initiation, we demonstrated increased responses to innate immune stimuli following viral suppression, as measured by the production of inflammatory cytokines. Plasma viral load itself had the strongest association with this change in innate functional capacity. We further identified epigenetic modifications in the TNFA promoter locus in monocytes that are associated with viremia, suggesting a molecular mechanism for the observed changes in innate immune function following initiation of ART. These data indicate that suppression of HIV-1 viremia is associated with changes in innate cellular function that may in part determine the restoration of protective immune responses.

A Randomized Trial of Comparing the Efficacy of Two Neurofeedback Protocols for Treatment of Clinical and Cognitive Symptoms of ADHD: Theta Suppression/Beta Enhancement and Theta Suppression/Alpha Enhancement

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Arash Mohagheghi

2017-01-01

Full Text Available Introduction. Neurofeedback (NF is an adjuvant or alternative therapy for children with Attention Deficit Hyperactivity Disorder (ADHD. This study intended to compare the efficacy of two different NF protocols on clinical and cognitive symptoms of ADHD. Materials and Methods. In this clinical trial, sixty children with ADHD aged 7 to 10 years old were randomly grouped to receive two different NF treatments (theta suppression/beta enhancement protocol and theta suppression/alpha enhancement protocol. Clinical and cognitive assessments were conducted prior to and following the treatment and also after an eight-week follow-up. Results. Both protocols alleviated the symptoms of ADHD in general (p<0.001, hyperactivity (p<0.001, inattention (p<0.001, and omission errors (p<0.001; however, they did not affect the oppositional and impulsive scales nor commission errors. These effects were maintained after an eight-week intervention-free period. The only significant difference between the two NF protocols was that high-frequency alpha enhancement protocol performed better in suppressing omission errors (p<0.001. Conclusion. The two NF protocols with theta suppression/beta enhancement and theta suppression/alpha enhancement have considerable and comparable effect on clinical symptoms of ADHD. Alpha enhancement protocol was more effective in suppressing omission errors.

Reinstatement of Conditioned Suppression in Mice

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Trinette Dirikx

2006-03-01

Full Text Available Return of fear after successful exposure therapy calls for a better understanding of the mechanisms of relapse. Classical conditioning research provides a useful framework for conceptualising the acquisition, extinction and reappearance of fear. The present paper focuses on reinstatement, the return of extinguished conditioned responses due to the experience of one or more unconditioned stimuli (USs after extinction. This phenomenon illustrates that unpredictable USs can lead to a return of fear after successful exposure. The data we present is one of the first demonstrations that conditioned suppression of instrumental behaviour can be used as an index of classical conditioning in laboratory mice. The procedure proves to be a promising instrument for assessing fear in mice, both in the context of research aimed at unravelling the functional characteristics of learning and memory in healthy mice and in the context of research aimed at unravelling the neurobiological substrate of psychiatric disorders, e.g., in studies with transgenic and knockout mice. Using this procedure, we report the first observation of reinstatement of conditioned suppression in this species.

Novel "Elements" of Immune Suppression within the Tumor Microenvironment.

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Gurusamy, Devikala; Clever, David; Eil, Robert; Restifo, Nicholas P

2017-06-01

Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread. We discuss the temporal and spatial roles of these elements within the tumor microenvironment and explore possible therapeutic interventions for effective and promising anticancer therapies. Cancer Immunol Res; 5(6); 426-33. ©2017 AACR . ©2017 American Association for Cancer Research.

Discontinuation of Pneumocystis jirovecii pneumonia prophylaxis with CD4 count <200 cells/µL and virologic suppression: a systematic review.

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Cecilia T Costiniuk

Full Text Available HIV viral load (VL is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP prophylaxis discontinuation, but suppression of plasma viremia with antiretroviral therapy may allow for discontinuation of PCP prophylaxis even with CD4 count <200 cells/µL.A systematic review was performed to determine the incidence of PCP in HIV-infected individuals with CD4 count <200 cells/µL and fully suppressed VL on antiretroviral therapy but not receiving PCP prophylaxis.Four articles examined individuals who discontinued PCP prophylaxis with CD4 count <200 cells/µL in the context of fully suppressed VL on antiretroviral therapy. The overall incidence of PCP was 0.48 cases per 100 person-years (PY (95% confidence interval (CI (0.06-0.89. This was lower than the incidence of PCP in untreated HIV infection (5.30 cases/100 PY, 95% CI 4.1-6.8 and lower than the incidence in persons with CD4 count <200 cells/µL, before the availability of highly active antiretroviral therapy (HAART, who continued prophylaxis (4.85/100 PY, 95% CI 0.92-8.78. In one study in which individuals were stratified according to CD4 count <200 cells/µL, there was a greater risk of PCP with CD4 count ≤100 cells/µL compared to 101-200 cells/µL.Primary PCP prophylaxis may be safely discontinued in HIV-infected individuals with CD4 count between 101-200 cells/µL provided the VL is fully suppressed on antiretroviral therapy. However, there are inadequate data available to make this recommendation when the CD4 count is ≤100 cells/µL. A revision of guidelines on primary PCP prophylaxis to include consideration of the VL is merited.

Dopa therapy and action impulsivity: subthreshold error activation and suppression in Parkinson's disease

NARCIS (Netherlands)

Fluchère, F.; Deveaux, M.; Burle, B.; Vidal, F.; van den Wildenberg, W.P.M.; Witjas, T.; Eusebio, A.; Azulay, J.-P.; Hasbroucq, T.

2015-01-01

Rationale: Impulsive actions entail (1) capture of the motor system by an action impulse, which is an urge to act and (2) failed suppression of that impulse in order to prevent a response error. Several studies indicate that dopaminergic treatment can induce action impulsivity in patients diagnosed

Reward enhances tic suppression in children within months of tic disorder onset.

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Greene, Deanna J; Koller, Jonathan M; Robichaux-Viehoever, Amy; Bihun, Emily C; Schlaggar, Bradley L; Black, Kevin J

2015-02-01

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis.

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Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

2017-01-01

To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy.

Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six-month follow-up study

NARCIS (Netherlands)

Hurenkamp, G. J.; Grundmeijer, H. G.; van der Ende, A.; Tytgat, G. N.; Assendelft, W. J.; van der Hulst, R. W.

2001-01-01

BACKGROUND: It remains controversial whether successful H. pylori eradication leads to relief of dyspepsia and the subsequent arrest or tapering of acid-suppressant drug therapy, or to an aggravation of acid-related dyspepsia requiring more acid-suppressant drug intake. AIM: To evaluate

CONTEMPORARY APPROACHES TO LEVOTHYROXINE THERAPY AFTER SURGERY IN PATIENTS WITH WELL-DIFFERENTIATED THYROID CANCER

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P. O. Rumyantsev

2013-01-01

Full Text Available Levothyroxine therapy with purpose to suppress thyroid stimulating hormone (TSH after surgery in patients with well-differentiated thyroid cancer is implemented since 1937. Accumulated results of levothyroxine suppressive therapy (LST application are attesting its heterogeneous efficacy in various risk groups of tumor recurrence: low, medium and high. Similar risk groups are emphasized towards adverse effect risk due to LST. The more intensivity and duration of TSH suppression the higher risk of adverse effects. First, they include osteopenia or osteoporosis and atrial fibrillation. Contemporary approaches to intensivity and duration of LTS are based on accounting of its potential efficiency into various clinical risk groups of tumor recurrence as well as adverse effects risk groups.

Combinatorial therapy with adenoviral-mediated PTEN and a PI3K inhibitor suppresses malignant glioma cell growth in vitro and in vivo by regulating the PI3K/AKT signaling pathway.

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Nan, Yang; Guo, Liyun; Song, Yunpeng; Wang, Le; Yu, Kai; Huang, Qiang; Zhong, Yue

2017-08-01

Glioblastoma is a highly invasive and challenging tumor of the central nervous system. The mutation/deletion of the tumor suppressor phosphatase and tensin homolog (PTEN) gene is the main genetic change identified in glioblastomas. PTEN plays a critical role in tumorigenesis and has been shown to be an important therapeutic target. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 is commonly used to inhibit glioma cell growth via regulation of the PI3K/AKT signaling pathway. In this study, we examined the growth inhibitory effects of a combinatorial therapy of adenoviral-mediated PTEN (Ad-PTEN) and LY294002 on LN229 and U251 glioma cells in vitro and on tumor xenografts in vivo. In vitro, LN229 and U251 glioma cells were treated by combinatorial therapy with Ad-PTEN and LY294002. The growth ability was determined by MTT assay. The cell cycle distribution was analyzed by flow cytometry. Cell invasive ability was analyzed by transwell invasion assay and cell apoptosis analysis via FITC-Annexin V analysis. In vivo, U251 subcutaneous glioblastoma xenograft was used to assay anti-tumor effect of combinatorial therapy with Ad-PTEN and LY294002 by mean volume of tumors, immunohistochemistry and TUNEL method. The combinatorial treatment clearly suppressed cell proliferation, arrested the cell cycle, reduced cell invasion and promoted cell apoptosis compared with the Ad-PTEN or LY294002 treatment alone. The treatment worked by inhibiting the PI3K/AKT pathway. In addition, the growth of U251 glioma xenografts treated with the combination of Ad-PTEN and LY294002 was significantly inhibited compared with those treated with Ad-PTEN or LY294002 alone. Our data indicated that the combination of Ad-PTEN and LY294002 effectively suppressed the malignant growth of human glioma cells in vitro and in tumor xenografts, suggesting a promising new approach for glioma gene therapy that warrants further investigation.

Care of the cancer survivor: metabolic syndrome following hormone-modifying therapy

OpenAIRE

Redig, Amanda J.; Munshi, Hidayatullah G.

2010-01-01

Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies may increase patients’ risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones, thus treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardi...

Study of the $B^0 \\rightarrow K^{\\ast 0}e^+ e^-$ decay with the LHCb detector and development of a novel concept of PID detector: the Focusing DIRC

CERN Document Server

AUTHOR|(CDS)2088184; Arnaud, Nicolas

Flavour-changing neutral current processes of the type $b \\to s\\gamma$ are forbidden at the tree level in the Standard Model (SM) and occur at leading order through radiative loop diagrams. Therefore, they are sensitive to new physics (NP), which may contribute with competing diagrams. Furthermore, the chirality of the weak interaction in the SM implies that the photon emitted has left-handed polarisation. However, a whole class of NP theories do not share this SM feature and may manifest unambiguously as a right-handed contribution to the polarisation. This thesis presents the first study of the ${b}{s\\gamma}$ photon polarisation through an angular analysis of the $B^0 \\rightarrow K^{\\ast 0}e^+ e^-$ channel. Even though $B^0 \\rightarrow K^{\\ast 0}e^+ e^-$ is not a radiative $b\\to s$ transition, the contribution from a virtual photon coupling to the lepton pair dominates in the low-$q^2$ region. Furthermore, the channel with electrons rather than muons allows to better isolate the virtual photon contribution ...

Acupuncture suppresses intravenous methamphetamine self-administration through GABA receptor's mediation.

Science.gov (United States)

Choi, Yi Jeong; Kim, Nam Jun; Zhao, Rong Jie; Kim, Da Hye; Yang, Chae Ha; Kim, Hee Young; Gwak, Young S; Jang, Eun Young; Kim, Jae Su; Lee, Yun Kyu; Lee, Hyun Jong; Lee, Sang Nam; Lim, Sung Chul; Lee, Bong Hyo

2018-01-01

Methamphetamine is one of the widely abused drugs. In spite of a number of studies, there is still little successful therapy to suppress the methamphetamine abuse. Acupuncture has shown to attenuate the reinforcing effects of psychostimulant. Based on, the present study investigated if acupuncture could suppress intravenous methamphetamine self-administration behavior. In addition, a possible neuronal mechanism was investigated. Male Sprague-Dawley rats weighing 270-300g were trained to intake food pellet. After catheter implantation, animal was trained to self-administer methamphetamine (0.05mg/kg) intravenously using fixed ratio 1 schedule in daily 2h session during 3 weeks. After training, rats who established baseline (infusion variation less than 20% of the mean for 3 consecutive days) received acupuncture treatment on the next day. Acupuncture was performed at each acupoint manually. In the second experiment, the selective antagonists of GABA A or GABA B receptor were given before acupuncture to investigate the possible neuronal involvement of GABA receptor pathway in the acupuncture effects. C-Fos expression was examined in the nucleus accumbens to support behavioral data. Acupuncture at HT7, but not at control acupoint LI5, reduced the self-administration behavior significantly. Also, the effects of acupuncture were blocked by the GABA receptor antagonists. C-Fos expression was shown to be parallel with the behavioral data. Results of this study have shown that acupuncture at HT7 suppressed methamphetamine self-administration through GABA receptor system, suggesting that acupuncture at HT7 can be a useful therapy for the treatment of methamphetamine abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

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Jim Young

Full Text Available Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

Spatial and Global Sensory Suppression Mapping Encompassing the Central 10° Field in Anisometropic Amblyopia.

Science.gov (United States)

Li, Jingjing; Li, Jinrong; Chen, Zidong; Liu, Jing; Yuan, Junpeng; Cai, Xiaoxiao; Deng, Daming; Yu, Minbin

2017-01-01

We investigate the efficacy of a novel dichoptic mapping paradigm in evaluating visual function of anisometropic amblyopes. Using standard clinical measures of visual function (visual acuity, stereo acuity, Bagolini lenses, and neutral density filters) and a novel quantitative mapping technique, 26 patients with anisometropic amblyopia (mean age = 19.15 ± 4.42 years) were assessed. Two additional psychophysical interocular suppression measurements were tested with dichoptic global motion coherence and binocular phase combination tasks. Luminance reduction was achieved by placing neutral density filters in front of the normal eye. Our study revealed that suppression changes across the central 10° visual field by mean luminance modulation in amblyopes as well as normal controls. Using simulation and an elimination of interocular suppression, we identified a novel method to effectively reflect the distribution of suppression in anisometropic amblyopia. Additionally, the new quantitative mapping technique was in good agreement with conventional clinical measures, such as interocular acuity difference (P suppression with dichoptic mapping paradigm and the results of the other two psychophysical methods (suppression mapping versus binocular phase combination, P suppression mapping versus global motion coherence, P = 0.005). The dichoptic suppression mapping technique is an effective method to represent impaired visual function in patients with anisometropic amblyopia. It offers a potential in "micro-"antisuppression mapping tests and therapies for amblyopia.

Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

International Nuclear Information System (INIS)

Nanda, Akash; Chen, M.-H.; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

2010-01-01

Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score ≥8, or clinical category ≥T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

Science.gov (United States)

Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

2013-10-01

Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

[Prevention and multimodal therapy of hyperthyroidism].

Science.gov (United States)

Palitzsch, K-D

2008-12-01

Subclinical and overt hyperthyroidism have been associated with various negative clinical outcomes as for example an increased risk of atrial fibrillation or increased cardiovascular mortality, especially in old age. In order to avoid hyperthyroidism it is strongly recommended not to start any iodine containing drug therapy or to avoid application of contrast agents unless the patient presents with an unremarkable clinical course. TSH suppressive therapy for the treatment of endemic goiter or differentiated low risk thyroid carcinoma is unnecessary, since it favours the development of subclinical hyperthyroidism. Overt hyperthyroidism is treated with antithyroid drugs and/or radioiodine therapy or surgery according to the underlying disease (toxic nodular goiter, Graves' disease).

Calculation of the activity incorporated in the therapy with I 131

International Nuclear Information System (INIS)

Chica, L.G.; Puerta, J.A.

1998-01-01

By means of the product S(T--S). A-s-(T-e-). the absorbed dose to thyroid delivered by I-131 incorporated is calculated. Where S(T--S) is the absorbed dose in the thyroid per nuclear transformations (tn.) of I-131 localized in the thyroid and as a potential function of the mass is expressed. A-s-(T-e-) is the number of tn. of I-131 in the thyroid since the moment of the incorporation until the time T-e- (the effective middle time); to find A-s-(T-e-) to normal as different pathological conditions, the metabolic model of the iodo proposed by the ICRP is used. Of the expression of the doses, the incorporated activity, I-o- is obtained

Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

International Nuclear Information System (INIS)

Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.; Mayer, H.K.

1986-01-01

The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using 5 H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S. aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function

Strategies for combinational cancer therapies

International Nuclear Information System (INIS)

Khleif, Samir

2014-01-01

The countless pre-clinical studies and many clinical trials that have applied tumor antigen-based therapies for the cancer treatment, and although the necessary tumor-specific immune response may be elicited in tumor-bearing hosts, this was not sufficient for the positive therapeutic outcome since there are multiple mechanisms that tumors develop to escape immune surveillance. The tumor-mediated inhibitory mechanisms involve co-inhibitory receptor-ligand interactions, such as PD-1/ PD-L1, secretion of inhibitory molecules, such as TGFb, and recruitment of suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), etc. Therefore, we hypothesized that successful cancer immunotherapy requires not only induction and enhancement of effector immune response but also simultaneous targeting of suppressor arm of immune system, thus in addition to enhancing antigen-specific immunity using vaccines or radiation therapy, one should also target tumor-mediated immune suppression to improve the overall efficacy of therapy. We developed multiple strategies to target various tumor-mediated immune inhibitory mechanisms that can enhance anti-tumor immunity and restructure tumor microenvironment to allow effector cells generated due to vaccination or radiation therapy to function potently. We evaluated the immune and therapeutic efficacy of multiple combinational therapies, including blocking and agonist antibodies to co-inhibitory/co-stimulatory molecules, such as PD-1, PD-L1, OX40, CTLA-4, GITR, inhibitors and neutralizing antibodies to inhibitory cytokines/molecules, such as IL-10, TGFb, IDO, and small molecules for selective inhibition of Tregs. In addition to evaluation of anti-tumor efficacy we are also investigated cellular and molecular mechanisms of action for these agents when combined with vaccine or radiation therapy and exploring the interactions between compounds within combinational therapies in animal tumor models. We are

HIV RNA Suppression during and after Pregnancy among Women in the HIV Outpatient Study, 1996 to 2015.

Science.gov (United States)

Patel, Monita; Tedaldi, Ellen; Armon, Carl; Nesheim, Steven; Lampe, Margaret; Palella, Frank; Novak, Richard; Sutton, Madeline; Buchacz, Kate

2018-01-01

To examine HIV viral suppression during/after pregnancy. Prospective observational cohort. We identified pregnancies from 1996 to 2015. We examined HIV RNA viral load (VL), VL suppression (≤500 copies/mL), and antiretroviral therapy (ART) status at pregnancy start, end, and 6 months postpartum. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) for VL nonsuppression. Among 253 pregnancies analyzed, 34.8% of women exhibited VL suppression at pregnancy start, 60.1% at pregnancy end, and 42.7% at 6 months postpartum. Median VL (log 10 copies/mL) was 2.80 (interquartile range [IQR]: 1.40-3.85) at pregnancy start, 1.70 (IQR: 1.40-2.82) at pregnancy end, and 2.30 (IQR: 1.40-3.86) at postpartum. Risk of postpartum VL nonsuppression was also lower among women on ART and with VL suppression at pregnancy end (versus those not; adjusted RR = 0.30, 95% CI: 0.17-0.53). Maintaining VL suppression among US women remains a challenge, particularly during postpartum. Achieving VL suppression earlier during pregnancy benefits women subsequently.

Stem cell therapy for inflammatory bowel disease

OpenAIRE

Duijvestein, Marjolijn

2012-01-01

Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal antigens. MSCs have the capacity to differentiate into a wide variety of distinct cell lineages and to suppress immune responses in vitro and in vivo. The main goal of this thesis was to study the s...

Adoptively transferred immune T cells eradicate established tumors in spite of cancer-induced immune suppression

Science.gov (United States)

Arina, Ainhoa; Schreiber, Karin; Binder, David C.; Karrison, Theodore; Liu, Rebecca B.; Schreiber, Hans

2014-01-01

Myeloid-derived CD11b+Gr1+ suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive ex vivo. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses. PMID:24367029

Experimental study of steam bubble velocities and dimensions in the draught trunk of the AST-500 reactor simulator

International Nuclear Information System (INIS)

Shanin, V.K.; Drobkov, V.P.; Kulakov, I.V.; Khalmeh, M.V.

1988-01-01

Local characteristics for two-phase steam water flow in the vertical channel with 0.45 m diameter and 2 m length, which is the draught trunk of the AST-500 reactor simulator, are investigated. Steam bubble velocities and dimensions were determined by the time-of-flight method using the twinned conductometric transducers. The data obtained testify to the existance of unstable circulation flows in the trunk peripheral region. These flows effect considerably the steam phase motion in the trunk middle part. At the same time the circulation flows to a lesser degree affect steam bubble motion in the trunk low peripheral part and to the lesser degree affect the steam phase in the axial zone near the outlet from the heating section. So the data obtained confirm the conclusion, made earlier, about steam-water flow acceleration in the draught trunk central part

miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker.

Science.gov (United States)

Li, Feng; Wang, Feiran; Zhu, Changlai; Wei, Qun; Zhang, Tianyi; Zhou, You Lang

2018-01-01

MicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC). In this study, we investigated whether miR-221 expression was associated with clini-copathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo. We found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC. These findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC.

Long-term side-effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study.

Science.gov (United States)

Malone, Shawn; Perry, Gad; Segal, Roanne; Dahrouge, Simone; Crook, Juanita

2005-09-01

To assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer. Patients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate-specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan-Meier method. In all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%). IAS has the potential to reduce side-effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.

Avaliação hematológica e dosagem bioquímica de ALT, AST e creatinina em elefante-marinho-do-sul, Mirounga leonina (linnaeus, 1758, encontrado no litoral de Salvador, Bahia

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Bruno Lopes Bastos

2006-02-01

Full Text Available Since 1999 the Aquatic Mammals Rescue Center - AMRC has been working in the rescue and rehabilitation of stranded cetaceans and pinnipeds on the coast of Bahia, Brazil. This paper presents and analyses the blood cells count and clinical chemistry of alanine aminotransferase (ALT, aspartate aminotransferase (AST and creatinine of a southern elephant seal, Mirounga leonina (LINNAEUS, 1758, found on February the 11th at Barra Beach, Salvador, BA. The specimen was an orphan male calf, with 137cm of length and estimated weight of 49kg. It presented bad nutritional conditions and a shark bite on the right shoulder area. Clinical management was performed for 56 days, anthelmintic Febendazole was utilized, and the bite was treated with iodined alcohol, Nitrofurazone solution and Kethanserin, simultaneously with Enrofloxacin 10%, Potenay®, Vitamin B Complex and Benerva®. On the 16th the animal presented a right unilateral conjuntivitis, treated with Cloranphenicol oftalmic pomade until the end of its stay in the captive. During this period a total of six blood samples were collected, three for total blood counts and the others for the biochemistry determination of ALT, AST and creatinine. According to the haematological analysis the seal developed an anaemia which was classified as microcytic and normochromic. Lymphopenia, eosinopenia and monocytopenia were also observed, possibly due to its handling and stress conditions. The clinical chemistry presented low values for AST and creatinine, although this did not represent the existence of any pathologic context or disease with clinical significance.

Maraviroc is associated with latent HIV-1 reactivation through NF-κB activation in resting CD4+ T cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

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Madrid-Elena, Nadia; García-Bermejo, María Laura; Serrano-Villar, Sergio; Díaz-de Santiago, Alberto; Sastre, Beatriz; Gutiérrez, Carolina; Dronda, Fernando; Coronel Díaz, María; Domínguez, Ester; López-Huertas, María Rosa; Hernández-Novoa, Beatriz; Moreno, Santiago

2018-02-14

Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and others have suggested that maraviroc could reactivate latent HIV-1. To test the latency reversing potential of maraviroc and the mechanisms involved, we performed a phase-II, single-center, open-label study in which maraviroc was administered for 10 days to 20 HIV-1-infected individuals on suppressive antiretroviral therapy (Eudra CT: 2012-003215-66). All patients completed full maraviroc dosing and follow up. The primary endpoint was to study whether maraviroc may reactivate HIV-1 latency, eliciting signalling pathways involved in the viral reactivation. An increase in HIV-1 transcription in resting CD4 + T-cells, estimated by HIV-1 unspliced RNA, was observed. Moreover, activation of the NF-κB transcription factor was observed in these cells. In contrast, AP-1 and NFAT activity was not detected. To elucidate the mechanism of NF-κB activation by maraviroc, we have evaluated in HeLa P4 C5 cells, which stably express CCR5, if maraviroc could be acting as a partial CCR5-agonist, with no other mechanisms or pathways involved. Our results show that maraviroc can induce NF-κB activity and NF-κB target genes expression by CCR5 binding, since the use of TAK779, a CCR5 inhibitor, blocked NF-κB activation and functionality. Taken together, we show that maraviroc may have a role in the activation of latent virus transcription through the activation of NF-κB as a result of binding CCR5. Our results strongly support a novel use of maraviroc as a potential latency reversal agent in HIV-1-infected patients. IMPORTANCE HIV-1 persistence in a small pool of long-lived latently infected resting CD4 + T-cells is a major barrier to viral eradication in HIV-1-infected patients on antiretroviral therapy. A potential strategy to cure HIV-1-infection is the use of latency reversing agents to eliminate the reservoirs established in resting CD4 + T-cells. As no drug has been shown to be completely

Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

DEFF Research Database (Denmark)

Woldbye, David Paul Drucker; Ängehagen, Mikael; Gøtzsche, Casper René

2010-01-01

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure...... recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2...... and neuropeptide Y had a more pronounced seizure-suppressant effect. These results demonstrate that overexpression of Y2 receptors (alone or in combination with neuropeptide Y) could be an alternative strategy for epilepsy treatment....

CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment.

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Han, Yan; Wu, Chunlei; Wang, Jing; Liu, Na

2017-05-01

The major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma invasion. Here, we investigated the relationship between CXCR7 and CXCR4 in osteosarcoma invasion induced by bone marrow microenvironment. Human bone marrow mesenchymal stem cells were co-cultured with osteosarcoma cells to mimic actual bone marrow microenvironment. Osteosarcoma cell invasion and CXCL12/CXCR4 activation were observed within this co-culture model. Interestingly, in this co-culture model, osteosarcoma cell invasion was not inhibited by suppressing CXCR4 expression with neutralizing antibody or specific inhibitor AMD3100. Downstream signaling extracellular signal-regulated kinase and signal transducer and activator of transcription 3 were not significantly affected by CXCR4 inhibition. However, suppressing CXCR4 led to CXCR7 upregulation. Constitutive expression of CXCR7 could maintain osteosarcoma cell invasion when CXCR4 was suppressed. Simultaneously, inhibiting CXCR4 and CXCR7 compromised osteosarcoma invasion in co-culture system and suppressed extracellular signal-regulated kinase and signal transducer and activator of transcription 3 signals. Moreover, bone marrow microenvironment, not CXCL12 alone, is required for CXCR7 activation after CXCR4 suppression. Taken together, suppressing CXCR4 is not enough to impede osteosarcoma invasion in bone marrow microenvironment since CXCR7 is activated to sustain invasion. Therefore, inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion.

One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks' treatment with esomeprazole

DEFF Research Database (Denmark)

van Zanten, S V; Flook, N; Talley, N J

2007-01-01

BACKGROUND: While empiric acid-suppressive therapy for uninvestigated dyspepsia patients with symptoms of epigastric pain or burning is standard practice, it is unknown whether an early response to therapy predicts outcome. AIM: To evaluate whether a 1-w acid suppression trial is effective...... for predicting 8-w response in such patients. METHODS: Helicobacter pylori-negative patients (aged 18-50 years) in primary care with uninvestigated epigastric pain or burning were randomized to esomeprazole 40 mg q.d.s. or b.d. for 1w, followed by esomeprazole 40 mg q.d.s. or placebo for 7w. Each day, patients......, respectively, and 47% (339 of 716) and 34% (124 of 368), respectively, at 8w (both P treatment were 58% and 70%, respectively, at 8w. CONCLUSION: A 1-w acid suppression trial is of limited clinical value for predicting 8-w response...

Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress

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Xiong-Zhi Li

2017-12-01

Full Text Available Background: Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. Methods: The ApoE-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67, senescence (p16INK4a, oxidant (NADPH oxidase 4, NOX4 and antioxidant (superoxide dismutase, SOD were observed by immunofluorescence staining. Results: Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE-/- mice. However, the decreased left ventricular ejection fraction (LVEF and fractional shortening (FS in ApoE–/– mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53-apoptosis pathway and oxidant-antioxidants in the hearts of ApoE-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16INK4a in the hearts of ApoE-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. Conclusion: AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress.

Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

International Nuclear Information System (INIS)

Gao, Xuemei; Wu, Xinchao; Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing; Maimaiti, Yusufu; Gao, Zairong; Zhang, Yongxue

2016-01-01

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine "1"3"1I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from "1"3"1I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced "1"3"1I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Gao, Xuemei [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Wu, Xinchao [Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Maimaiti, Yusufu [Department of Thyroid and Breast Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Gao, Zairong, E-mail: gaobonn@163.com [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Zhang, Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China)

2016-01-15

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy

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Selwyn M. Prea

2015-01-01

Full Text Available Age-related macular degeneration (AMD is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet” form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF. However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly, potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.

A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV.

Science.gov (United States)

Tsai, Alexander C; Weiser, Sheri D; Petersen, Maya L; Ragland, Kathleen; Kushel, Margot B; Bangsberg, David R

2010-12-01

Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. Community-based prospective cohort study with assessments conducted every 3 months. Community-based research field site in San Francisco, California. One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, 13) inclusion criteria, observed from April 2002 through August 2007. Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

Suppression of E. multilocularis hydatid cysts after ionizing radiation exposure.

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Xin Zhou

Full Text Available BACKGROUND: Heavy-ion therapy has an advantage over conventional radiotherapy due to its superb biological effectiveness and dose conformity in cancer therapy. It could be a potential alternate approach for hydatid cyst treatment. However, there is no information currently available on the cellular and molecular basis for heavy-ion irradiation induced cell death in cystic echinococcosis. METHODODOLOGY/PRINCIPAL FINDINGS: LD50 was scored by protoscolex death. Cellular and ultrastructural changes within the parasite were studied by light and electron microscopy, mitochondrial DNA (mtDNA damage and copy number were measured by QPCR, and apoptosis was determined by caspase 3 expression and caspase 3 activity. Ionizing radiation induced sparse cytoplasm, disorganized and clumped organelles, large vacuoles and devoid of villi. The initial mtDNA damage caused by ionizing radiation increased in a dose-dependent manner. The kinetic of DNA repair was slower after carbon-ion radiation than that after X-rays radiation. High dose carbon-ion radiation caused irreversible mtDNA degradation. Cysts apoptosis was pronounced after radiation. Carbon-ion radiation was more effective to suppress hydatid cysts than X-rays. CONCLUSIONS: These studies provide a framework to the evaluation of attenuation effect of heavy-ion radiation on cystic echinococcosis in vitro. Carbon-ion radiation is more effective to suppress E. multilocularis than X-rays.

Suppressing effects of glucan on micronuclei induced by Co sup 60 in mice

Energy Technology Data Exchange (ETDEWEB)

Chorvatovicova, D. (Slovak Academy of Sciences, Bratislava (Czechoslovakia). Inst. of Ecobiology)

1991-10-01

The effects of glucan on the frequency of micronuclei in polychromatic erythrocytes of A/Ph mouse bone marrow induced by Co{sup 60} irradiation were examined. Suppressing effect of three glucan derivatives was statistically significant (P<0.01) by intravenous application of glucan one hour after irradiation. The most expressive effect was obvious by K{sub 3} substituent (DS 0.89). Intraperitoneal application of glucan has to be done earlier than one hour after irradiation. The suppressive effects of glucans can be explained by their ability to trap OH radicals and so decrease the clastogenic effect of irradiation. The results may be useful for therapeutic application of glucan with radiation therapy. (orig.).

Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model.

Science.gov (United States)

Aryanpour, Roya; Pasbakhsh, Parichehr; Zibara, Kazem; Namjoo, Zeinab; Beigi Boroujeni, Fatemeh; Shahbeigi, Saeed; Kashani, Iraj Ragerdi; Beyer, Cordian; Zendehdel, Adib

2017-10-01

Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice. In addition, CPZ+PRO caused a significant reduction in the mRNA expression levels of M1-markers (iNOS, CD86, MHC-II and TNF-α) in the corpus callosum region, whereas the expression of M2-markers (Trem-2, CD206, Arg-1 and TGF-β) was significantly increased, in comparison to CPZ mice. Moreover, CPZ+PRO resulted in a significant decrease in the number of iNOS + and Iba-1 + /iNOS + cells (M1), whereas TREM-2 + and Iba-1 + /TREM-2 + cells (M2) significantly increased, in comparison to CPZ group. Furthermore, CPZ+PRO caused a significant decrease in mRNA and protein expression levels of NLRP3 and IL-18 (~2-fold), in comparison to the CPZ group. Finally, CPZ+PRO therapy was accompanied with reduced levels of demyelination, compared to CPZ, as confirmed by immunofluorescence to myelin basic protein (MBP) and Luxol Fast Blue (LFB) staining, as well as transmission electron microscopy (TEM) analysis. In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Curcumin Modulates the Radiosensitivity of Colorectal Cancer Cells by Suppressing Constitutive and Inducible NF-κB Activity

International Nuclear Information System (INIS)

Sandur, Santosh K.; Deorukhkar, Amit; Pandey, Manoj K.; Pabon, Ana Maria B.S.; Shentu, Shujun; Guha, Sushovan; Aggarwal, Bharat B.; Krishnan, Sunil

2009-01-01

Purpose: Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy. Methods and Materials: Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-κB (NF-κB) activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance. Results: Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-κB activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-κB activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of κB alpha, inhibition of inhibitor of κB kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-κB-regulated gene products (Bcl-2, Bcl-x L , inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1). Conclusions: Our results suggest that transient inducible NF-κB activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.

The Prospect of Immunoglobulin Y for Therapy of Canine parvovirus Infection in Dogs

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I Gusti Ayu Agung Suartini

2015-06-01

Full Text Available Canine parvovirus (CPV is a highly infectious virus. The virus causes death in dogs worldwide. The mortality rate due to infection of CPV in dog reaches 91%. Prevention of CPV infection in puppies has been done by vaccination which is effectively proven. Protective mechanisms of maternal antibodies contribute to the failure of vaccination. Highly stable characteristics of parvovirus enable the virus still exist in the environment. Various therapies are performed only to suppress the clinical symptoms but can not reduce puppy mortalities. This review discusses CPV alternative therapy and the advantages using immunoglobulin Y (IgY specific antibodies isolated from chicken egg yolk. Immunoglobulin Y will neutralize the virus, so it can not infect host cells. Intravenous IgY therapy has shown to suppress the spread of CPV infection and prevent death.

Suppressed Belief

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Komarine Romdenh-Romluc

2009-12-01

Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

Gene Therapy With Regulatory T Cells: A Beneficial Alliance

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Moanaro Biswas

2018-03-01

Full Text Available Gene therapy aims to replace a defective or a deficient protein at therapeutic or curative levels. Improved vector designs have enhanced safety, efficacy, and delivery, with potential for lasting treatment. However, innate and adaptive immune responses to the viral vector and transgene product remain obstacles to the establishment of therapeutic efficacy. It is widely accepted that endogenous regulatory T cells (Tregs are critical for tolerance induction to the transgene product and in some cases the viral vector. There are two basic strategies to harness the suppressive ability of Tregs: in vivo induction of adaptive Tregs specific to the introduced gene product and concurrent administration of autologous, ex vivo expanded Tregs. The latter may be polyclonal or engineered to direct specificity to the therapeutic antigen. Recent clinical trials have advanced adoptive immunotherapy with Tregs for the treatment of autoimmune disease and in patients receiving cell transplants. Here, we highlight the potential benefit of combining gene therapy with Treg adoptive transfer to achieve a sustained transgene expression. Furthermore, techniques to engineer antigen-specific Treg cell populations, either through reprogramming conventional CD4+ T cells or transferring T cell receptors with known specificity into polyclonal Tregs, are promising in preclinical studies. Thus, based upon these observations and the successful use of chimeric (IgG-based antigen receptors (CARs in antigen-specific effector T cells, different types of CAR-Tregs could be added to the repertoire of inhibitory modalities to suppress immune responses to therapeutic cargos of gene therapy vectors. The diverse approaches to harness the ability of Tregs to suppress unwanted immune responses to gene therapy and their perspectives are reviewed in this article.

Consequences of stereotype suppression and internal suppression motivation : A self-regulation approach

NARCIS (Netherlands)

Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.

The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in

The Efficacy of Thyrotropin Suppression Therapy in Treatment of Differentiated Thyroid Cancer after Total Thyroidectomy

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Abo-Touk Niveen A.

2015-06-01

Full Text Available Background: The aim of this prospective study was to assess the effect of the TSH suppression on both disease-free and overall survivals in patients with nonmetastatic differentiated thyroid cancer (DTC after total thyroidectomy.

Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

DEFF Research Database (Denmark)

Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K

2012-01-01

microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment...... of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody exerts...... its activity by suppressing stroma cell recruitment to the site of the growing tumor. Our epitope mapping studies suggested that the antibody recognition site overlaps with the target binding interface of human S100A4. We conclude here that this antibody could serve as a solid basis for development...

Iron deposition in cranial bone marrow with sickle cell disease: MR assessment using a fat suppression technique

International Nuclear Information System (INIS)

Kaneko, K.; Humbert, J.H.; Kogutt, M.S.; Robinson, A.E.

1993-01-01

Thirteen patients with sickle cell disease (SCD) undergoing transfusion therapy and 8 control patients were examined by magnetic resonance imaging to discriminate bone marrow change due to iron deposition from hematologic marrow hyperplasia. Using T1-weighted spin echo images, only two subjects showed extremely low signal intensity marrow compatible with iron deposition. However, using T2-weighted fast spin echo images with fat suppression, cranial bone marrow in SCD patients with transfusion therapy showed considerably lower signal than that of controls. The main cause of marrow signal decrease in SCD patients with transfusion therapy was considered to be iron deposition due to repeated transfusion therapy rather than red marrow hyperplasia. (orig.)

Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

Energy Technology Data Exchange (ETDEWEB)

Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.; Mayer, H.K.

1986-03-01

The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S. aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.

Impact of regurgitation on health-related quality of life in gastro-oesophageal reflux disease before and after short-term potent acid suppression therapy.

Science.gov (United States)

Kahrilas, Peter J; Jonsson, Andreas; Denison, Hans; Wernersson, Börje; Hughes, Nesta; Howden, Colin W

2014-05-01

Limited data exist on the impact of regurgitation on health-related quality of life (HRQOL) in gastro-oesophageal reflux disease (GORD). We assessed the relationship between regurgitation frequency and HRQOL before and after acid suppression therapy in GORD. We used data from two randomised trials of AZD0865 25-75 mg/day versus esomeprazole 20 or 40 mg/day in non-erosive reflux disease (NERD) (n=1415) or reflux oesophagitis (RO) (n=1460). The Reflux Disease Questionnaire was used to select patients with frequent and intense heartburn for inclusion and to assess treatment response. The Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire was used to assess HRQOL. At baseline, 93% of patients in both the NERD and RO groups experienced regurgitation. Mean QOLRAD scores were similar for NERD and RO at baseline and at week 4 and disclosed decremental HRQOL with increasing frequency of regurgitation; a clinically relevant difference of >0.5 in mean QOLRAD scores was seen with regurgitation ≥4 days/week versus <4 days/week. The prevalence of frequent, persistent regurgitation (≥4 days/week) at week 4 among heartburn responders (≤1 day/week of mild heartburn) was 28% in NERD and 23% in RO. QOLRAD scores were higher among heartburn responders. There was a similar pattern of impact related to regurgitation frequency in heartburn responders compared with the group as a whole. Frequent regurgitation was associated with a clinically relevant, incremental decline in HRQOL beyond that associated with heartburn before and after potent acid suppression in both NERD and RO. NCT00206284 and NCT00206245.

Physician experience and rates of plasma HIV-1 RNA suppression among illicit drug users: an observational study

Directory of Open Access Journals (Sweden)

Sangsari Sassan

2012-01-01

Full Text Available Abstract Background Despite the availability of antiretroviral therapy (ART, suboptimal treatment outcomes have been observed among HIV-seropositive illicit drug users. As there is an urgent need to improve responses to antiretroviral therapy among this population, we undertook this study to evaluate the role of physician experience on rates of plasma HIV-1 RNA suppression following initiation of ART. Methods Using data from a community-recruited cohort of HIV-positive illicit drug users, we used Cox proportional hazards regression to model the time to plasma viral HIV RNA Results Between May 1996 and December 2008, 267 individuals initiated ART among whom 227 (85% achieved a plasma HIV RNA Conclusions In this setting of universal HIV/AIDS care, illicit drug users with more experienced physicians exhibited faster rates of plasma viral load suppression. These findings argue for specialized services to help optimize HIV treatment outcomes among this population.

A binocular approach to treating amblyopia: antisuppression therapy.

Science.gov (United States)

Hess, Robert F; Mansouri, Behzad; Thompson, Benjamin

2010-09-01

We developed a binocular treatment for amblyopia based on antisuppression therapy. A novel procedure is outlined for measuring the extent to which the fixing eye suppresses the fellow amblyopic eye. We hypothesize that suppression renders a structurally binocular system, functionally monocular. We demonstrate using three strabismic amblyopes that information can be combined normally between their eyes under viewing conditions where suppression is reduced. Also, we show that prolonged periods of viewing (under the artificial conditions of stimuli of different contrast in each eye) during which information from the two eyes is combined leads to a strengthening of binocular vision in such cases and eventual combination of binocular information under natural viewing conditions (stimuli of the same contrast in each eye). Concomitant improvement in monocular acuity of the amblyopic eye occurs with this reduction in suppression and strengthening of binocular fusion. Furthermore, in each of the three cases, stereoscopic function is established. This provides the basis for a new treatment of amblyopia, one that is purely binocular and aimed at reducing suppression as a first step.

Measurements of the S-wave fraction in $B^{0}\\rightarrow K^{+}\\pi^{-}\\mu^{+}\\mu^{-}$ decays and the $B^{0}\\rightarrow K^{\\ast}(892)^{0}\\mu^{+}\\mu^{-}$ differential branching fraction

CERN Document Server

Aaij, Roel; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bitadze, Alexander; Bizzeti, Andrea; Blake, Thomas; Blanc, Frederic; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Boettcher, Thomas; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Bossu, Francesco; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chobanova, Veronika; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dungs, Kevin; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Déléage, Nicolas; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Färber, Christian; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gizdov, Konstantin; Gligorov, V.V.; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gorelov, Igor Vladimirovich; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Göbel, Carla; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hussain, Nazim; Hutchcroft, David; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozachuk, Anastasiia; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Leflat, Alexander; Lefrançois, Jacques; Lefèvre, Regis; Lemaitre, Florian; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Maltsev, Timofei; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Mulder, Mick; Mussini, Manuel; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen-Mau, Chung; Niess, Valentin; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Oldeman, Rudolf; Onderwater, Gerco; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petrov, Aleksandr; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Pomery, Gabriela Johanna; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Remon Alepuz, Clara; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vicente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Rogozhnikov, Alexey; Roiser, Stefan; Romanovskiy, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schellenberg, Margarete; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubert, Konstantin; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefko, Pavol; Stefkova, Slavorima; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valat, Sebastien; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Venkateswaran, Aravindhan; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Voneki, Balazs; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Vázquez Sierra, Carlos; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zarebski, Kristian Alexander; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhang, Yu; Zhelezov, Alexey; Zheng, Yangheng; Zhokhov, Anatoly; Zhukov, Valery; Zucchelli, Stefano

2016-11-08

A measurement of the differential branching fraction of the decay ${B^{0}\\rightarrow K^{\\ast}(892)^{0}\\mu^{+}\\mu^{-}}$ is presented together with a determination of the S-wave fraction of the $K^+\\pi^-$ system in the decay $B^{0}\\rightarrow K^{+}\\pi^{-}\\mu^{+}\\mu^{-}$. The analysis is based on $pp$-collision data corresponding to an integrated luminosity of 3\\,fb$^{-1}$ collected with the LHCb experiment. The measurements are made in bins of the invariant mass squared of the dimuon system, $q^2$. Precise theoretical predictions for the differential branching fraction of $B^{0}\\rightarrow K^{\\ast}(892)^{0}\\mu^{+}\\mu^{-}$ decays are available for the $q^2$ region $1.1

Use of high-dose, twice-yearly albendazole and ivermectin to suppress Wuchereria bancrofti microfilarial levels.

Science.gov (United States)

Dembele, Benoit; Coulibaly, Yaya I; Dolo, Housseini; Konate, Siaka; Coulibaly, Siaka Y; Sanogo, Dramane; Soumaoro, Lamine; Coulibaly, Michel E; Doumbia, Salif Seriba; Diallo, Abdallah A; Traore, Sekou F; Diaman Keita, Adama; Fay, Michael P; Nutman, Thomas B; Klion, Amy D

2010-12-01

Annual mass treatment with albendazole and ivermectin is the mainstay of current strategies to interrupt transmission of Wuchereria bancrofti in Africa. More-effective microfilarial suppression could potentially reduce the time necessary to interrupt transmission, easing the economic burden of mass treatment programs in countries with limited resources. To determine the effect of increased dose and frequency of albendazole-ivermectin treatment on microfilarial clearance, 51 W. bancrofti microfilaremic residents of an area of W. bancrofti endemicity in Mali were randomized to receive 2 doses of annual, standard-dose albendazole-ivermectin therapy (400 mg and 150 μg/kg; n = 26) or 4 doses of twice-yearly, increased-dose albendazole-ivermectin therapy (800 mg and 400 μg/kg; n = 25). Although microfilarial levels decreased significantly after therapy in both groups, levels were significantly lower in the high-dose, twice-yearly group at 12, 18, and 24 months. Furthermore, there was complete clearance of detectable microfilariae at 12 months in the 19 patients in the twice-yearly therapy group with data available at 12 months, compared with 9 of 21 patients in the annual therapy group (P < .001, by Fisher's exact test). This difference between the 2 groups was sustained at 18 and 24 months, with no detectable microfilariae in the patients receiving twice-yearly treatment. Worm nests detectable by ultrasonography and W. bancrofti circulating antigen levels, as measured by enzyme-linked immunosorbent assay, were decreased to the same degree in both groups at 24 months, compared with baseline. These findings suggest that increasing the dosage and frequency of albendazole-ivermectin treatment enhances suppression of microfilariae but that this effect may not be attributable to improved adulticidal activity.

Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial.

Science.gov (United States)

Depalma, Ralph G; Hayes, Virginia W; Chow, Bruce K; Shamayeva, Galina; May, Patricia E; Zacharski, Leo R

2010-06-01

This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer-specific death. Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed. At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43-134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with

Cyclosporine-A therapy-induced multiple bilateral breast and accessory axillary breast fibroadenomas: a case report

Directory of Open Access Journals (Sweden)

Darwish Ahmed

2010-08-01

Full Text Available Abstract Introduction Breast adenoma is common. However, in the setting of post-transplantation immune suppression it may be expressed differently. Case presentation A 35-year-old Sudanese woman, with a history of renal transplantation two and half years prior to presentation, was on a single immune suppression therapy in the form of cyclosporine-A since the transplantation. During a regular follow-up visit, she was noticed to have gingival hypertrophy and bilateral breast and axillary swellings. She underwent successful surgical resection of the bilateral fibroadenomas. Conclusions Cyclosporine-A therapy post renal transplantation is associated with an increased incidence of benign breast changes as fibroadenoma. Regular follow-up and appropriate selection of immunosuppressant therapy are essential in the post transplantation management of these patients.

Deconstructing continuous flash suppression.

Science.gov (United States)

Yang, Eunice; Blake, Randolph

2012-03-08

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

Neuroplasticity in Constraint-Induced Movement Therapy

DEFF Research Database (Denmark)

Blicher, Jakob; Near, Jamie; Næss-Schmidt, Erhard

2014-01-01

In healthy subjects, decreasing GABA facilitates motor learning[1]. Recent studies, using PET[2], TMS[3-5], and pharmacological challenges[6], have pointed indirectly to a decrease in neuronal inhibitory activity after stroke. Therefore, we hypothesize that a suppression of GABA levels post strok...... might be beneficial to motor recovery during Constraint-Induced Movement Therapy (CIMT)....

Evaluation of radiation therapy for advanced well-differentiated thyroid carcinoma

International Nuclear Information System (INIS)

Tatsuno, Ikuo; Tada, Akira; Choto, Shuichi; Takanaka, Tsuyoshi

1987-01-01

Eighty-two patients with advanced well-differentiated thyroid carcinoma were treated. Sixty-six patients survived for more than 10 years and 10-year-survival rate was 80.5 %. Multidisciplinary treatment, consisting of surgery, radioiodine, external irradiation and TSH suppression was studied. We emphasized that radioiodine treatment after thyroid-ectomy was unique and an ideal therapeutic model for locally advanced, distant metastatic and recurrent cases as far as radioiodine was accumulated on thyroid cancer tissue. External irradiation was sometimes effective for the remnant thyroid carcinoma and metastases. Occassionally, well-differentiated thyroid carcinoma showed good response to TSH suppression therapy using thyroid hormone. The significance of conversion of well-differentiated carcinoma of thyroid to anaplastic carcinoma was noticed. We recognized that radiation therapy was effective for advanced well-differentiated thyroid carcinoma in multidisciplinary treatment. (author)

Evaluation of radiation therapy for advanced well-differentiated thyroid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Tatsuno, Ikuo; Tada, Akira; Choto, Shuichi; Takanaka, Tsuyoshi

1987-02-01

Eighty-two patients with advanced well-differentiated thyroid carcinoma were treated. Sixty-six patients survived for more than 10 years and 10-year-survival rate was 80.5 %. Multidisciplinary treatment, consisting of surgery, radioiodine, external irradiation and TSH suppression was studied. We emphasized that radioiodine treatment after thyroid-ectomy was unique and an ideal therapeutic model for locally advanced, distant metastatic and recurrent cases as far as radioiodine was accumulated on thyroid cancer tissue. External irradiation was sometimes effective for the remnant thyroid carcinoma and metastases. Occassionally, well-differentiated thyroid carcinoma showed good response to TSH suppression therapy using thyroid hormone. The significance of conversion of well-differentiated carcinoma of thyroid to anaplastic carcinoma was noticed. We recognized that radiation therapy was effective for advanced well-differentiated thyroid carcinoma in multidisciplinary treatment.

Dexamethasone suppression test

Science.gov (United States)

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

Exogenous regucalcin suppresses the growth of human liver cancer HepG2 cells in vitro.

Science.gov (United States)

Yamaguchi, Masayoshi; Murata, Tomiyasu

2018-04-05

Regucalcin, which its gene is localized on the X chromosome, plays a pivotal role as a suppressor protein in signal transduction in various types of cells and tissues. Regucalcin gene expression has been demonstrated to be suppressed in various tumor tissues of animal and human subjects, suggesting a potential role of regucalcin in carcinogenesis. Regucalcin, which is produced from the tissues including liver, is found to be present in the serum of human subjects and animals. This study was undertaken to determine the effects of exogenous regucalcin on the proliferation in cloned human hepatoma HepG2 cells in vitro. Proliferation of HepG2 cells was suppressed after culture with addition of regucalcin (0.01 – 10 nM) into culture medium. Exogenous regucalcin did not reveal apoptotic cell death in HepG2 cells in vitro. Suppressive effects of regucalcin on cell proliferation were not enhanced in the presence of various signaling inhibitors including tumor necrosis factor-α (TNF-α), Bay K 8644, PD98059, staurosporine, worthomannin, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) or gemcitabine, which were found to suppress the proliferation. In addition, exogenous regucalcin suppressed the formation of colonies of cultured hepatoma cells in vitro. These findings demonstrated that exogenous regucalcin exhibits a suppressive effect on the growth of human hepatoma HepG2 cells, proposing a strategy with the gene therapy for cancer treatment.

Deconstructing continuous flash suppression

OpenAIRE

Yang, Eunice; Blake, Randolph

2012-01-01

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

Radioiodine therapy of differentiated thyroid cancer: AIIMS experience

International Nuclear Information System (INIS)

Padhy, A.K.; Nair, P.G.G.; ); Bal, C.S.; Pant, G.S.; Basu, A.K.

1999-01-01

After a slow start in late sixties, the procedure of 131 I therapy for Differentiated Thyroid Cancer (DTC) has gained increasing popularity with every passing year at All India Institute of Medical Sciences. This has become an integral part of TC management at AIIMS like at most other centres all over the world. There is a general consensus that near total thyroidectomy along with 131 I therapy and suppressive doses of thyroid hormones provide the best mode of treatment for DTC

Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Tucker, Jo A.; Jochems, Caroline [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Gulley, James L. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Schlom, Jeffrey, E-mail: js141c@nih.gov; Tsang, Kwong Y. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

2012-12-11

Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies.

Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

International Nuclear Information System (INIS)

Tucker, Jo A.; Jochems, Caroline; Gulley, James L.; Schlom, Jeffrey; Tsang, Kwong Y.

2012-01-01

Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

DEFF Research Database (Denmark)

Engsig, Frederik N; Zangerle, Robert; Katsarou, Olga

2014-01-01

BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years...... of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing...... age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3...

Screening for suppression in young children: the Polaroid Suppression test

NARCIS (Netherlands)

Pott, J.W.R.; Oosterveen, DK; Van Hof-van Duin, J

1998-01-01

Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

No Evidence for Decay of the Latent Reservoir in HIV-1–Infected Patients Receiving Intensive Enfuvirtide-Containing Antiretroviral Therapy

Science.gov (United States)

Gandhi, Rajesh T.; Bosch, Ronald J.; Aga, Evgenia; Albrecht, Mary; Demeter, Lisa M.; Dykes, Carrie; Bastow, Barbara; Para, Michael; Lai, Jun; Siliciano, Robert F.; Siliciano, Janet D.; Eron, Joseph J.

2010-01-01

Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. PMID:20001856

Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells

Directory of Open Access Journals (Sweden)

Hai-Bo Xing

2018-01-01

Full Text Available Pancreatic adenocarcinoma has an exceedingly poor prognosis, accounting for five-year survival of less than 5%. Presently, improving the efficacy of pancreatic adenocarcinoma treatment has been the focus of medical researchers worldwide. Recently, it has been suggested that deregulation of interleukin- (IL- 6 is caused by a key gene involved in the beginning and development of pancreatic adenocarcinoma. Herein, we investigated whether suppression of IL-6 could augment gemcitabine sensitivity in the PANC-1 cells. We found considerably higher expression of IL-6 in pancreatic adenocarcinoma tissues than that in the adjacent nontumorous tissues. Suppression of IL-6 by shRNA resulted in apoptosis as well as inhibition of cell proliferation and tumorigenicity. In addition, suppression of IL-6 remarkably promoted antitumor effect of gemcitabine, indicating that the combination of shRNA targeting IL-6 with gemcitabine may provide a potential clinical approach for pancreatic cancer therapy.

Increased T cell trafficking as adjunct therapy for HIV-1

OpenAIRE

Fryer, HR; Wolinsky, SM; McLean, AR

2018-01-01

Although antiretroviral drug therapy suppresses human immunodeficiency virus-type 1 (HIV-1) to undetectable levels in the blood of treated individuals, reservoirs of replication competent HIV-1 endure. Upon cessation of antiretroviral therapy, the reservoir usually allows outgrowth of virus and approaches to targeting the reservoir have had limited success. Ongoing cycles of viral replication in regions with low drug penetration contribute to this persistence. Here, we use a mathematical mode...

Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV.

Directory of Open Access Journals (Sweden)

Shoshana Y Kahana

Full Text Available The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States.The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural and Esri Crime (e.g., global crime index databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1 being on antiretroviral therapy (ART currently; (2 being on ART for at least 6 months; (3 missed HIV care appointments (not having missed any vs. having missed one or more appointments over the past 12 months; and (4 viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability.Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%; ART use for ≥6 months (n = 861, 45.53%; at least one missed HIV care appointment (n = 936, 49.50; and viral suppression (n = 577, 30.51%. After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent

Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

Science.gov (United States)

Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

2012-06-01

What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

Calcium hydroxide suppresses Porphyromonas endodontalis lipopolysaccharide-induced bone destruction.

Science.gov (United States)

Guo, J; Yang, D; Okamura, H; Teramachi, J; Ochiai, K; Qiu, L; Haneji, T

2014-05-01

Porphyromonas endodontalis and its main virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical diseases and alveolar bone loss. Calcium hydroxide is commonly used for endodontic therapy. However, the effects of calcium hydroxide on the virulence of P. endodontalis LPS and the mechanism of P. endodontalis LPS-induced bone destruction are not clear. Calcium hydroxide rescued the P. endodontalis LPS-suppressed viability of MC3T3-E1 cells and activity of nuclear factor-κB (NF-κB) in these cells, resulting in the reduced expression of interleukin-6 and tumor necrosis factor-α. In addition, calcium hydroxide inhibited P. endodontalis LPS-induced osteoclastogenesis by decreasing the activities of NF-κB, p38, and ERK1/2 and the expression of nuclear factor of activated T-cell cytoplasmic 1 in RAW264.7 cells. Calcium hydroxide also rescued the P. endodontalis LPS-induced osteoclastogenesis and bone destruction in mouse calvaria. Taken together, our present results indicate that calcium hydroxide suppressed bone destruction by attenuating the virulence of P. endodontalis LPS on bone cells.

Anti-Tumor Necrosis Factor-alpha in therapy of severe alcoholic hepatitis: a case report

Directory of Open Access Journals (Sweden)

M. Romano

2013-05-01

Full Text Available AIM OF THE STUDY The aim of this study is to evaluate the tolerance and effects of a single dose of infliximab combined with steroid therapy. PATIENTS AND METHODS A 44-years old man patient with chronic alcohol abuse, obesity, dyslipidemia and diabetes with AH (Maddrey’s score 32 received an association of prednisolone (80 mg/day ev and infliximab (5 mg/kg once. RESULTS At 2 weeks bilirubin decreased from 18.1 mg/dL to 6 mg/dL. At 4 weeks AST decreased from 1042 U/L to 154 U/L, ALT from 1112 U/L to 151 U/L, Maddrey’s score decreased to 17.4. Infliximab was well tolerated, but after 5 weeks the patient suffered an adverse event characterized by fever, panniculitis, septicaemia of Staphylococcus aureus treated with specific therapy. At 60 days the patient was asymptomatic and the liver function tests were normal (Maddrey’s score 10. At 6 months of follow-up: Maddrey’s score 6. CONCLUSIONS In AH, infliximab was well tolerated and associated with significant improvement in LFTs and Maddrey’s score, but these promising results should encourage large trials assessing better the strategy of therapy and criteria for enrolment of the patients.

Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.

Science.gov (United States)

Wang, Ying; Rishi, Arun K; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I; Wali, Anil

2011-11-01

Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM.

Mitochondria-Targeted Nitroxide, Mito-CP, Suppresses Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

Science.gov (United States)

Starenki, Dmytro

2013-01-01

Context: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. Objective: We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC. Design: In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined. Results: Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP–induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals. Conclusion: Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy. PMID:23509102

AChR-specific immunosuppressive therapy of myasthenia gravis.

Science.gov (United States)

Luo, Jie; Lindstrom, Jon

2015-10-15

Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

Science.gov (United States)

Peterson, Christopher W; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Jerome, Keith R; Hu, Shiu-Lok; Holmes, Michael C; Estes, Jacob D; Kiem, Hans-Peter

2018-04-01

Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

Directory of Open Access Journals (Sweden)

Christopher W Peterson

2018-04-01

Full Text Available Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP model of latent infection using simian/human immunodeficiency virus (SHIV and combination antiretroviral therapy (cART in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05, relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.

Science.gov (United States)

Mengoli, Carlo; Andreis, Samantha; Scaggiante, Renzo; Cruciani, Mario; Bosco, Oliviero; Ferretto, Roberto; Leoni, Davide; Maffongelli, Gaetano; Basso, Monica; Torti, Carlo; Sarmati, Loredana; Andreoni, Massimo; Palù, Giorgio; Parisi, Saverio Giuseppe

2017-01-01

To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log 10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log 10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log 10 HIV RNA at T0 on log 10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log 10 HIV RNA at T0 (P = 0.003) was apparent. PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Highly sensitive determination of TSH in the follow-up of TSH-suppressive therapy of patients with differentiated thyroid cancer

International Nuclear Information System (INIS)

Mann, K.; Saller, B.; Mehl, U.; Hoermann, R.; Moser, E.

1988-01-01

Basal and TRH-stimulated TSH levels were determined in 72 patients with differentiated thyroid cancer on hormonal treatment, using a highly sensitive immunoradiometric assay (IRMAclon, Henning). 43 patients were under treatment with levothyroxine (T 4 ), 29 patients with triiodothyronine (T 3 ). In 33/43 patients (77%) under T 4 - and in 18/29 patients (62%) under T 3 -treatment basal TSH levels were below 0.1 mU/l. 3 patients showed a significant response (to above 0.5 mU/l) in the TRH test despite basal values of less than 0.1 mU/l. In 2 patients with elevated basal TSH levels (0.23 and 0.60 mU/l, resp.) in the IRMAclon, total suppression of TSH secretion was suggested by a failure of TSH to rise after TRH. By retesting these samples in an own TSH IRMA, basal and stimulated TSH values were below 0.1 mU/l. In conclusion, basal and TRH-stimulated TSH levels are well correlated in most patients with thyroid cancer under hormonal treatment. However, in some cases (5/72) determination of basal TSH could not clearly define the degree of thyrotropic suppression. Thus, TRH testing is still necessary to establish definitely complete TSH suppression in patients with thyroid carcinoma under suppressive treatment. (orig.) [de

Repeated 89Sr therapy in breast cancer patient with multiple bone metastases

International Nuclear Information System (INIS)

Lee, Jae Soung; Yang, Weon Il; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo; Hong, Soung Woon

2000-01-01

The single 89 Sr therapy has been used for pain relief in patients with multiple bony metastases and it is known to be very effective without serious complications except mild bone marrow suppression. But usually repeated therapy is needed because it is not a completely curative therapy. This study was performed to evaluate the effects of repeated 89 Sr therapy on therapeutic outcome compared to first therapy. This study was performed retrospectively with fifteen breast cancer patients treated more than twice with 89 SrCl 2 against multiple bony metastases. There were total 42 cases-there were eight, four, two and one patients treated twice, three times, four times and six times respectively. The time interval between therapy was 179.1±107.5 (90-550) days. We scored zero to five about performance, analgesics, subjective pain, sleep pattern respectively and summed as the pain score (0-20). Before therapy and one month and three months after therapy the pain score was evaluated and blood leukocyte and platelet was estimated. Bone scan was performed before therapy and one, three and six months after therapy. The pain score was 6.5±2.4 (2-10) before first therapy. Among 42 cases the pain score was improved in 22 cases (52.4%), not changed in 8 cases (19.0%) and aggravated in 12 cases (28.6%). The pain score was not affected by therapy number. Bone scan showed various changes without statistical correlation with pain score. One month after therapy blood leukocyte and platelet was decreased more than 20% than before therapy in six cases (28.6%) and seven cases (16.7%) among 21 cases, respectively. The leukocyte and platelet was not more decreased as increased therapy number. The repeated 89 Sr therapy is not so different from the first therapy in effects and bone marrow suppression. Bone scan finding was independent to the pain score

Emerging genetic therapies to treat Duchenne muscular dystrophy

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Nelson, Stanley F.; Crosbie, Rachelle H.; Miceli, M. Carrie; Spencer, Melissa J.

2010-01-01

Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called `exon skipping' and `nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy. PMID:19745732

Aging and repeated thought suppression success.

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Ann E Lambert

Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies.

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Monjazeb, Arta M; Kent, Michael S; Grossenbacher, Steven K; Mall, Christine; Zamora, Anthony E; Mirsoian, Annie; Chen, Mingyi; Kol, Amir; Shiao, Stephen L; Reddy, Abhinav; Perks, Julian R; T N Culp, William; Sparger, Ellen E; Canter, Robert J; Sckisel, Gail D; Murphy, William J

2016-09-01

Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects. These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR. ©2016 American Association for Cancer Research.

Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

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Huang, Hao; Wang, Xue-Ping; Li, Xiao-Hui; Chen, Hao; Zheng, Xin; Lin, Jian-Hua; Kang, Ting; Zhang, Lin; Chen, Pei-Song

2017-08-14

The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

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Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

1999-02-04

Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

Filgrastim as a Rescue Therapy for Persistent Neutropenia in a Case of Dengue Hemorrhagic Fever with Acute Respiratory Distress Syndrome and Myocarditis

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Desh Deepak

2011-01-01

Full Text Available Pathogenesis of dengue involves suppression of immune system leading to development of characteristic presentation of haematological picture of thrombocytopenia and leucopenia. Sometimes, this suppression in immune response is responsible for deterioration in clinical status of the patient in spite of all specific and supportive therapy. Certain drugs like steroids are used for rescue therapy in conditions like sepsis. We present a novel use of filgrastim as a rescue therapy in a patient with dengue hemorrhagic fever (DHF with acute respiratory distress syndrome (ARDS, myocarditis, and febrile neutropenia and not responding to standard management.

The Role of Thought Suppression, Meta-Cognitive Factors and Negative Emotions in Prediction of Substance Dependency Disorder

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Omid Saed

2011-08-01

Full Text Available Introduction: This study investigated the role of thought suppression, meta- cognitive factors, and negative emotions in predicting of substance dependency disorder. Method: Subjects were 70 patients with substance dependence disorder and 70 normal individuals (total 140. Substance dependants were selected of outpatient treatment centers and the normal sample was selected of the general population too. Sampling methods in both samples were convenience sampling. All people were assessed by MCQ-30, White Bear Suppression Inventory, and Beck’s Anxiety and Depression Questionnaires. For data analysis, discriminant analysis were used. Results: Negative meta-cognitive beliefs about worry, depression, and thought suppression were the most significant predictors of substance dependence disorder. Conclusion: Through meta-cognitive beliefs, thought suppression and negative emotion (especially depression, substance dependency disorder can be predicted. Based on this model can be used to take a substance dependency disorder prevention approach and psychotherapy approach (based on cognitive and meta-cognitive therapies. In addition, the findings of this research can be applied in clinical and counseling environments to help substance dependant clients.

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

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Newman, Neil B; Sidhu, Manpreet K; Baby, Rekha; Moss, Rebecca A; Nissenblatt, Michael J; Chen, Ting; Lu, Shou-En; Jabbour, Salma K

2016-04-01

To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

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Newman, Neil B.; Sidhu, Manpreet K.; Baby, Rekha [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Moss, Rebecca A.; Nissenblatt, Michael J. [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Lu, Shou-En [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

2016-04-01

Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: a national multicentre cohort study.

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Prendki, V; Ferry, T; Sergent, P; Oziol, E; Forestier, E; Fraisse, T; Tounes, S; Ansart, S; Gaillat, J; Bayle, S; Ruyer, O; Borlot, F; Le Falher, G; Simorre, B; Dauchy, F-A; Greffe, S; Bauer, T; Bell, E N; Martha, B; Martinot, M; Froidure, M; Buisson, M; Waldner, A; Lemaire, X; Bosseray, A; Maillet, M; Charvet, V; Barrelet, A; Wyplosz, B; Noaillon, M; Denes, E; Beretti, E; Berlioz-Thibal, M; Meyssonnier, V; Fourniols, E; Tliba, L; Eden, A; Jean, M; Arvieux, C; Guignery-Kadri, K; Ronde-Oustau, C; Hansmann, Y; Belkacem, A; Bouchand, F; Gavazzi, G; Herrmann, F; Stirnemann, J; Dinh, A

2017-09-01

During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81-88]. The predominant pathogen involved was Staphylococcus (62.1%) (Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.

Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy

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Solomon, Ajantha; Ghneim, Khader; Ahlers, Jeffrey; Cameron, Mark J.; Smith, Miranda Z.; Spelman, Tim; McMahon, James; Velayudham, Pushparaj; Brown, Gregor; Roney, Janine; Watson, Jo; Prince, Miles H.; Hoy, Jennifer F.; Chomont, Nicolas; Fromentin, Rémi; Procopio, Francesco A.; Zeidan, Joumana; Palmer, Sarah; Odevall, Lina; Johnstone, Ricky W.; Martin, Ben P.; Sinclair, Elizabeth; Deeks, Steven G.; Hazuda, Daria J.; Cameron, Paul U.; Sékaly, Rafick-Pierre; Lewin, Sharon R.

2014-01-01

Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells. Trial Registration ClinicalTrials.gov NCT01365065 PMID:25393648

Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy.

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Julian H Elliott

2014-10-01

Full Text Available Human immunodeficiency virus (HIV persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART. The primary endpoint was change in cell associated unspliced (CA-US HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065. Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90% with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1. CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.ClinicalTrials.gov NCT01365065.

TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription.

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Gómez-Herreros, Fernando; Zagnoli-Vieira, Guido; Ntai, Ioanna; Martínez-Macías, María Isabel; Anderson, Rhona M; Herrero-Ruíz, Andrés; Caldecott, Keith W

2017-08-10

DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation 'hotspot', MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.DNA double-strand breaks (DSBs) induced by topoisomerase II (TOP2) are rejoined by TDP2-dependent non-homologous end-joining (NHEJ) but whether this promotes or suppresses translocations is not clear. Here the authors show that TDP2 suppresses chromosome translocations from DSBs introduced during gene transcription.

Doppiaggio in italiano del film 'Astérix et Obélix - Au service de Sa Majesté'. Trasposizione degli elementi culturali e umoristici

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Alessandra Rollo

2016-01-01

Full Text Available Abstract – At present, audiovisual translation is one of the most interesting and stimulating domains within the field of Translation Studies. Resting on a rich semiotic apparatus, marked by the interplay of a double channel of communication – audio/visual – with different types of signs – verbal/non-verbal codes, the audiovisual text is a complex one, whose transfer from one language into another represents a challenging task for every professional in this field. Especially in dubbing, the translator/adapter has to work on the interlinguistic level as well as on the intersemiotic level (iconic, paralinguistic elements, etc.: as many codes having great semantic potential and transmitting useful cultural information, as we shall see in the film which we have taken as the object of our analyses: Astérix et Obélix: Au Service de Sa Majesté (2012. This fourth film adaptation (except cartoons of Astérix’s adventures offers a series of gags playing on the parody of typical traditions, symbols, linguistic clichés and cultural stereotypes associated with British culture. Italian dubbing resorts to different translation strategies, some of which come under a foreignizing approach, aiming at preserving the original’s colour and mood, whereas others are in line with a domesticating approach, in order to bring the product closer to the final audience. Indeed, instead of stressing the idea of a polarization or a dichotomy between two contrasting perspectives, we find it advisable to envisage a gradation between two instances which occur at the same time and coexist in a complementary way during the translation process.   Keywords: audiovisual translation; dubbing; cultural elements; humorous elements; foreignization/domestication.     Résumé – La traduction audiovisuelle se configure à l’heure actuelle comme l’un des domaines les plus intéressants et les plus stimulants dans le panorama des etudes traductologiques. Reposant sur

Trans/figurations of modern times? Disputes over the works of Maria Komornicka (pen name Piotr Odmieniec Włast

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Mateusz Chmurski

2016-03-01

Full Text Available The article is a reflection of how the work by Maria Komornicka (pen name Piotr Odmieniec Włast was perceived in the past two decades on the basis of an analysis of a monograph by Edward Boniecki (1996, Izabela Filipiak (2006 and Brigitta Helbig-Mischewski (2010 in the context of changes in the interpretation of modern Polish literature. In the article, attention is drawn to three groups of issues which can only be identified on the basis of contemporary perception, incomplete as it is, due to the fact that all the works of Komornicka have not been published. The forms and meaning of broadly defined autobiographical writing has been re-defined, while Polish and regional literary modernism has been revised together with the involvement of literary researchers in the subject of their analyses. The author of the article suggests a schematic differentiation between updating, prospective and retrospective strategies in Komornicka’s work and a reflection on the indirect involvement in social and cultural discourses and discussions developed by contemporary researchers into Komornicka’s work.

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models.

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Chang, Andrew D; Berges, Victoria A; Chung, Sunho J; Fridman, Gene Y; Baraban, Jay M; Reti, Irving M

2016-06-01

Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2(-/y) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.

Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression by Ganoderma Lucidum Polysaccharides

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Li-Xin Sun

2014-01-01

Full Text Available Background/Aims: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-β, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. Methods: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. Results: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. Conclusion: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy.

Hepatic Enzyme Alterations in HIV Patients on Antiretroviral Therapy: A Case-Control Study in a Hospital Setting in Ghana.

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Osakunor, Derick Nii Mensah; Obirikorang, Christian; Fianu, Vincent; Asare, Isaac; Dakorah, Mavis

2015-01-01

Diagnosing hepatic injury in HIV infection can be a herculean task for clinicians as several factors may be involved. In this study, we sought to determine the effects of antiretroviral therapy (ART) and disease progression on hepatic enzymes in HIV patients. A case-control study conducted from January to May 2014 at the Akwatia Government Hospital, Eastern region, Ghana, The study included 209 HIV patients on ART (designated HIV-ART) and 132 ART-naive HIV patients (designated HIV-Controls). Data gathered included demography, clinical history and results of blood tests for hepatic enzymes. We employed the Fisher's, Chi-square, unpaired t-test and Pearson's correlation in analysis, using GraphPad Prism and SPSS. A P value 0.05). There was a significant positive correlation between hepatic enzymes (ALP, ALT, AST and GGT) for both groups (p enzymes for both groups was small. Antiretroviral therapy amongst this population has minimal effects on hepatic enzymes and does not suggest modifications in therapy. Hepatic injury may occur in HIV, even in the absence of ART and other traditional factors. Monitoring of hepatic enzymes is still important in HIV patients.

MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis

Science.gov (United States)

Qiu, Jing-Xin; Kim, Edward J.; Yu, Ai-Ming

2016-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Better understanding of pancreatic cancer biology may help identify new oncotargets towards more effective therapies. This study investigated the mechanistic actions of microRNA-1291 (miR-1291) in the suppression of pancreatic tumorigenesis. Our data showed that miR-1291 was downregulated in a set of clinical pancreatic carcinoma specimens and human pancreatic cancer cell lines. Restoration of miR-1291 expression inhibited pancreatic cancer cell proliferation, which was associated with cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 sharply suppressed the tumorigenicity of PANC-1 cells in mouse models. A proteomic profiling study revealed 32 proteins altered over 2-fold in miR-1291-expressing PANC-1 cells that could be assembled into multiple critical pathways for cancer. Among them anterior gradient 2 (AGR2) was reduced to the greatest degree. Through computational and experimental studies we further identified that forkhead box protein A2 (FOXA2), a transcription factor governing AGR2 expression, was a direct target of miR-1291. These results connect miR-1291 to the FOXA2-AGR2 regulatory pathway in the suppression of pancreatic cancer cell proliferation and tumorigenesis, providing new insight into the development of miRNA-based therapy to combat pancreatic cancer. PMID:27322206

Pressure suppressing device

International Nuclear Information System (INIS)

Naito, Makoto.

1980-01-01

Purpose: To prevent the pressure in the reactor container from excessively increasing even when vapor leaks from the dry well to a space of the suppression chamber, without passing though the suppression pool at the time of loss of coolant accident. Constitution: When vapor of a high temperature and a high pressure at the time of loss of coolant accident flows from the dry well to the suppression chamber without passing through suppression pool water, vapor dose not condense with pool water, and therefore the pressure within the chamber abnormally increases. For this reason, this abnormal pressure is detected by a pressure detector thereby to start the operations of a blower and a pump. By starting the blower, the pressure in the dry well becomes lower than the pressure in the chamber, and vapor entirely passes through the pool water and entirely condenses with the pool water. By starting the pump, the pool water is sprayed over the space of the chamber, and vapor in the space is condensed. (Yoshino, Y.)

Recent advances in the microbiological diagnosis of bloodstream infections.

Science.gov (United States)

Florio, Walter; Morici, Paola; Ghelardi, Emilia; Barnini, Simona; Lupetti, Antonella

2018-05-01

Rapid identification (ID) and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections (BSIs) are essential for the prompt administration of an effective antimicrobial therapy, which can result in clinical and financial benefits. Immediately after blood sampling, empirical antimicrobial therapy, chosen on clinical and epidemiological data, is administered. When ID and AST results are available, the clinician decides whether to continue or streamline the antimicrobial therapy, based on the results of the in vitro antimicrobial susceptibility profile of the pathogen. The aim of the present study is to review and discuss the experimental data, advantages, and drawbacks of recently developed technological advances of culture-based and molecular methods for the diagnosis of BSI (including mass spectrometry, magnetic resonance, PCR-based methods, direct inoculation methods, and peptide nucleic acid fluorescence in situ hybridization), the understanding of which could provide new perspectives to improve and fasten the diagnosis and treatment of septic patients. Although blood culture remains the gold standard to diagnose BSIs, newly developed methods can significantly shorten the turnaround time of reliable microbial ID and AST, thus substantially improving the diagnostic yield.

The role of suppression in amblyopia.

Science.gov (United States)

Li, Jingrong; Thompson, Benjamin; Lam, Carly S Y; Deng, Daming; Chan, Lily Y L; Maehara, Goro; Woo, George C; Yu, Minbin; Hess, Robert F

2011-06-13

This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Distinguishing among potential mechanisms of singleton suppression.

Science.gov (United States)

Gaspelin, Nicholas; Luck, Steven J

2018-04-01

Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Is mindfulness-based therapy an effective intervention for obsessive-intrusive thoughts: a case series.

Science.gov (United States)

Wilkinson-Tough, Megan; Bocci, Laura; Thorne, Kirsty; Herlihy, Jane

2010-01-01

Despite the efficacy of cognitive-behavioural interventions in improving the experience of obsessions and compulsions, some people do not benefit from this approach. The present research uses a case series design to establish whether mindfulness-based therapy could benefit those experiencing obsessive-intrusive thoughts by targeting thought-action fusion and thought suppression. Three participants received a relaxation control intervention followed by a six-session mindfulness-based intervention which emphasized daily practice. Following therapy all participants demonstrated reductions in Yale-Brown Obsessive-Compulsive Scale scores to below clinical levels, with two participants maintaining this at follow-up. Qualitative analysis of post-therapy feedback suggested that mindfulness skills such as observation, awareness and acceptance were seen as helpful in managing thought-action fusion and suppression. Despite being limited by small participant numbers, these results suggest that mindfulness may be beneficial to some people experiencing intrusive unwanted thoughts and that further research could establish the possible efficacy of this approach in larger samples. Copyright (c) 2009 John Wiley & Sons, Ltd.

Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model.

Science.gov (United States)

Takahashi, Junko; Murakami, Mami; Mori, Takashi; Iwahashi, Hitoshi

2018-02-09

Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

Measurement of the forward-backward asymmetry in $Z/\\gamma^{\\ast} \\rightarrow \\mu^{+}\\mu^{-}$ decays and determination of the effective weak mixing angle

CERN Document Server

Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Buchanan, Emma; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fohl, Klaus; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Gascon, David; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Edmund; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavorima; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zucchelli, Stefano

2015-11-27

The forward-backward charge asymmetry for the process $q\\bar{q} \\rightarrow Z/\\gamma^{\\ast} \\rightarrow \\mu^{+}\\mu^{-}$ is measured as a function of the invariant mass of the dimuon system. Measurements are performed using proton proton collision data collected with the LHCb detector at $\\sqrt {s} = 7$ and 8 TeV, corresponding to integrated luminosities of 1 fb$^{-1}$ and 2 fb$^{-1}$ respectively. Within the Standard Model the results constrain the effective electroweak mixing angle to be $\\text{sin} ^2\\theta ^\\text{eff} _W = 0.23142 \\pm 0.00073 \\pm 0.00052 \\pm 0.00056$, where the first uncertainty is statistical, the second systematic and the third theoretical. This result is in agreement with the current world average, and is one of the most precise determinations at hadron colliders to date.

Comprehensive suppression of all apoptosis-induced proliferation pathways as a proposed approach to colorectal cancer prevention and therapy.

Directory of Open Access Journals (Sweden)

Michael Bordonaro

Full Text Available Mutations in the WNT/beta-catenin pathway are present in the majority of all sporadic colorectal cancers (CRCs, and histone deacetylase inhibitors induce apoptosis in CRC cells with such mutations. This apoptosis is counteracted by (1 the signaling heterogeneity of CRC cell populations, and (2 the survival pathways induced by mitogens secreted from apoptotic cells. The phenomena of signaling heterogeneity and apoptosis-induced survival constitute the immediate mechanisms of resistance to histone deacetylase inhibitors, and probably other chemotherapeutic agents. We explored the strategy of augmenting CRC cell death by inhibiting all survival pathways induced by the pro-apoptotic agent LBH589, a histone deacetylase inhibitor: AKT, JAK/STAT, and ERK signaling. The apoptosis-enhancing ability of a cocktail of synthetic inhibitors of proliferation was compared to the effects of the natural product propolis. We utilized colorectal adenoma, drug-sensitive and drug-resistant colorectal carcinoma cells to evaluate the apoptotic potential of the combination treatments. The results suggest that an effective approach to CRC combination therapy is to combine apoptosis-inducing drugs (e.g., histone deacetylase inhibitors, such as LBH589 with agents that suppress all compensatory survival pathways induced during apoptosis (such as the cocktail of inhibitors of apoptosis-associated proliferation. The same paradigm can be applied to a CRC prevention approach, as the apoptotic effect of butyrate, a diet-derived histone deacetylase inhibitor, is augmented by other dietary agents that modulate survival pathways (e.g., propolis and coffee extract. Thus, dietary supplements composed by fermentable fiber, propolis, and coffee extract may effectively counteract neoplastic growth in the colon.

Dual antiretroviral therapy for HIV infection.

Science.gov (United States)

Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo

2017-08-01

For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3)

International Nuclear Information System (INIS)

Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-01-01

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF 1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free. (author)

The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.

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Ron Firestein

2008-04-01

Full Text Available Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD(+-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR, a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a beta-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates beta-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of beta-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of beta-catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in beta-catenin-driven malignancies.

Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-κB and Akt pathways

International Nuclear Information System (INIS)

Wang Xia; Chen Wenshu; Lin Yong

2007-01-01

Blockage of either nuclear factor-κB (NF-κB) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-κB activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-κB. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-κB activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-κB activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-κB and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-κB and Akt, which may be applied in lung cancer therapy

Effects of the addition of remifentanil to propofol anesthesia on seizure length and postictal suppression index in electroconvulsive therapy.

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Porter, Richard; Booth, David; Gray, Hamish; Frampton, Chris

2008-09-01

Propofol is a widely used anesthetic agent for electroconvulsive therapy (ECT). However, there are concerns that its anticonvulsant effect may interfere with the efficacy of ECT. We aimed to investigate the effects on seizure activity of the addition of the opiate remifentanil to propofol anesthesia for ECT. A retrospective analysis of 633 treatments in 73 patients was conducted. At each treatment, patients had received anesthesia with propofol alone or propofol plus remifentanil, depending on which anesthetist was providing anesthesia. Analysis of variance was performed to examine the effects of the anesthetic used, the electrode placement, the dose of electricity administered, and the stage in the course of treatment. Dependent variables were electroencephalogram seizure length and postictal suppression index (PSI). Addition of remifentanil resulted in a small but significantly lower dose of propofol being used to induce unconsciousness. Addition of remifentanil affected seizure length, mainly related to an effect when placement was right unilateral (F = 5.70; P = 0.017). There was also a significantly increased PSI (F = 4.3; P = 0.039), which was not dependent on dose or on placement. The data suggest that addition of remifentanil to propofol anesthesia significantly alters seizure indices. This may be secondary to a reduction in the amount of propofol required or to an independent effect of remifentanil. The increase in PSI in particular suggests that addition of remifentanil may improve clinical response. However, this can only be examined in a randomized controlled trial.

Thyroid suppression test with dextrothyroxine

International Nuclear Information System (INIS)

Rosenthal, D.; Fridman, J.; Ribeiro, H.B.

1978-01-01

The classic thyroid suppression test with triiodothyronine (l-T 3 ) has been shown to be efficient as an auxiliary method in the diagnosis of thyroid diseases, but should not be performed on elderly patients or on those with heart disease or a tendency to tachycardia. Since these subjects seem able to support a short period of dextro-thyronine (d-T 4 ) feeding, we compared the effect of d-T 4 and l-T 3 on the 24 hours thyroid uptake in euthyroid and hyperthyroid subjects. After basal radio-iodine uptake determination, 99 patients without hyperthyroidism and 27 with Graves' disease were randomly divided in 2 groups; one received 100μg of l-T 3 per day and the other 4 mg of d-T 4 per day, both groups being treated for a period of 10 days. At the end of this suppression period the 24 hours radio-iodine uptake was measured again and the percentual suppression index (S.I.) calculated. Since the comparison of the two groups showed no difference between the suppressive effect of l-T 3 and d-T 4 in euthyroid subjects, while dextro-thyronine, as levo-triiodothyronine, did not suppress the 24 hours uptake of hyperthyroid patients, l-T 3 or d-T 4 can be used interchangeably to test thyroid suppressibility. In the euthyroid subjects the normal range for the post-suppression uptake was 0-17.1% and for the suppression index 54,7.100% [pt

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

Energy Technology Data Exchange (ETDEWEB)

Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp

2015-05-15

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

International Nuclear Information System (INIS)

Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

2015-01-01

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action

Effects of antiretroviral therapy on immunity in patients infected with HIV.

Science.gov (United States)

Feola, D J; Thornton, A C; Garvy, B A

2006-01-01

Drug therapy for human immunodeficiency virus (HIV) is highly effective in suppressing viral replication and restoring immune function in patients with HIV. However, this same treatment can also be associated with immunotoxicity. For example, zidovudine and various other antiretroviral agents are capable of causing bone marrow suppression. Agents used to treat opportunistic infections in these individuals, including ganciclovir, foscarnet, and sulfamethoxazole-trimethoprim, can cause additional hematotoxicity. Drug-drug interactions must also be considered and managed in order to control iatrogenic causes of immunotoxicity. In this review, we examine the normal immune response to HIV, and the benefits of antiretroviral therapy in prolonging immune function. We then discuss immune-related adverse effects of drugs used to treat HIV and the opportunistic infections that are common among these patients. Finally, we address in vitro, animal, and clinical evidence of toxicity associated with various combination use of these agents.

How does methylation suppress the electron-induced decomposition of 1-methyl-nitroimidazoles?

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Kossoski, F.; Varella, M. T. do N.

2017-10-01

The efficient decomposition of nitroimidazoles (NIs) by low energy electrons is believed to underlie their radiosensitizing properties. Recent dissociative electron attachment (DEA) measurements showed that methylation at the N1 site unexpectedly suppresses the electron-induced reactions in 4(5)-NI. We report theoretical results that provide a clear interpretation of that astounding finding. Around 1.5 eV, DEA reactions into several fragments are initiated by a π* resonance, not considered in previous studies. The autoionization lifetime of this anion state, which limits the predissociation dynamics, is considerably shorter in the methylated species, thereby suppressing the DEA signals. On the other hand, the lifetime of the π* resonance located around 3 eV is less affected by methylation, which explains why DEA is still observed at these energies. Our results demonstrate how even a simple methylation can significantly modify the probabilities for DEA reactions, which may be significant for NI-based cancer therapy.

Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

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Lee, So-Yeon; Kim, Sun Ki [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Jee, Won-Hee [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Catholic University of Korea, Diagnostic Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seoul (Korea, Republic of); Kim, Jung-Man [Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

2011-02-15

To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using {kappa} coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with ({kappa} = 0.87) or without ({kappa} = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

International Nuclear Information System (INIS)

Lee, So-Yeon; Kim, Sun Ki; Jee, Won-Hee; Kim, Jung-Man

2011-01-01

To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using κ coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with (κ = 0.87) or without (κ = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

[Long-term effects of combined therapy in patients with beta-thalassemia major].

Science.gov (United States)

Bagnulo, S; Giannini, A M; Moscatelli, F; Stragapede, L; Acquafredda, A; Dammacco, A

1998-01-01

We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.

Management issues with exogenous steroid therapy

OpenAIRE

Patt, Hiren; Bandgar, Tushar; Lila, Anurag; Shah, Nalini

2013-01-01

Glucocorticoids (GCs) are extensively used for various inflammatory and autoimmune disorders, but long term use of these agents is not without complications. Almost every GC formulations (e.g. oral, topical, inhaled, etc.) can cause systemic side effects. It can range from minor side effects (e.g. weight gain) to life-threatening effects (e.g. adrenal suppression, sepsis, etc.), which may require immediate intervention. Therefore, the decision to institute steroid therapy always requires care...

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

Science.gov (United States)

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

2010-12-15

Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania

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Kelly Ben L

2010-02-01

Full Text Available Abstract Background Chronic inflammation activated by macrophage innate pathogen recognition receptors such as TLR4 can lead to a range of inflammatory diseases, including atherosclerosis, Crohn's disease, arthritis and cancer. Unlike many microbes, the kinetoplastid protozoan pathogen Leishmania has been shown to avoid and even actively suppress host inflammatory cytokine responses, such as LPS-induced IL-12 production. The nature and scope of Leishmania-mediated inflammatory cytokine suppression, however, is not well characterized. Advancing our knowledge of such microbe-mediated cytokine suppression may provide new avenues for therapeutic intervention in inflammatory disease. Methods We explored the kinetics of a range of cytokine and chemokine responses in primary murine macrophages stimulated with LPS in the presence versus absence of two clinically distinct species of Leishmania using sensitive multiplex cytokine analyses. To confirm that these effects were parasite-specific, we compared the effects of Leishmania uptake on LPS-induced cytokine expression with uptake of inert latex beads. Results Whilst Leishmania uptake alone did not induce significant levels of any cytokine analysed in this study, Leishmania uptake in the presence of LPS caused parasite-specific suppression of certain LPS-induced pro-inflammatory cytokines, including IL-12, IL-17 and IL-6. Interestingly, L. amazonensis was generally more suppressive than L. major. We also found that other LPS-induced proinflammatory cytokines, such as IL-1α, TNF-α and the chemokines MIP-1α and MCP-1 and also the anti-inflammatory cytokine IL-10, were augmented during Leishmania uptake, in a parasite-specific manner. Conclusions During uptake by macrophages, Leishmania evades the activation of a broad range of cytokines and chemokines. Further, in the presence of a strong inflammatory stimulus, Leishmania suppresses certain proinflammatory cytokine responses in a parasite

Ultraviolet light-induced suppression of antigen presentation

International Nuclear Information System (INIS)

Spellman, C.W.; Tomasi, T.B.

1983-01-01

Ultraviolet (UV) light irradiation of animals results in the development of specific T suppressor cells that inhibit antitumor immune responses. It is thought that suppression may arise as a consequence of altered antigen presentation by UV-irradiated epidermal cells. This hypothesis is based on evidence demonstrating that specific lymphoid tissues from UV-irradiated hosts exhibit impaired antigen-presenting function and that animals cannot be contact sensitized when antigens are applied to a UV-irradiated skin site. Langerhans cells of the skin are likely candidates as targets of UV-induced defects in antigen presentation as they bear Fc and C3b receptors, express Ia antigens, are of bone marrow origin, and are capable of presenting antigen in vitro. We speculate on the possible clinical usefulness of UV-induced tolerance to specific antigens such as those encountered in monoclonal antibody therapy and tissue transplantation

Optimal systemic therapy for premenopausal women with hormone receptor-positive breast cancer.

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Jankowitz, Rachel C; McGuire, Kandace P; Davidson, Nancy E

2013-08-01

Although systemic therapy is one of the cornerstones of therapy for premenopausal women with early stage breast cancer, there remain many unknowns regarding its optimal use. By accident of clinical trial design, much clinical investigation in premenopausal women has focused on chemotherapy. More recently the value of endocrine therapy (tamoxifen and ovarian suppression/ablation via surgery, LHRH agonists, or chemotherapy-induced menopause) has become apparent, and some form of endocrine therapy is viewed as standard for virtually all premenopausal women with early stage invasive breast cancer that expresses estrogen and/or progesterone receptor. Critical open questions include type and duration of endocrine therapy and the development of prognostic/predictive markers to help identify patients who are likely to benefit from chemotherapy in addition to endocrine therapy. For some years, five years of tamoxifen has been viewed as the standard endocrine therapy for premenopausal hormone-responsive breast cancer, although the ATLAS trial suggests that an additional five years of tamoxifen can be considered. The MA17 trial also suggests that an additional five years of an aromatase inhibitor can be considered for women who become postmenopausal during tamoxifen therapy. Information about the value of ovarian suppression continues to emerge, most recently with the demonstration of excellent outcome with goserelin plus tamoxifen in the ABCSG12 trial. The SOFT and TEXT trials, whose accrual is now complete, should help to define optimal endocrine therapy. In addition, use of the 21-gene recurrence score assay may help to delineate the additional value of chemotherapy for patients with node-negative breast cancer, and its utility in the setting of women with 1-3 positive lymph nodes is under study in the RxPONDER trial. Nonetheless, the need for other predictive biomarkers to select appropriate therapy remains real. Finally, attention to long term benefits and side effects

A partial differential equation model and its reduction to an ordinary differential equation model for prostate tumor growth under intermittent hormone therapy.

Science.gov (United States)

Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

2014-10-01

Hormonal therapy with androgen suppression is a common treatment for advanced prostate tumors. The emergence of androgen-independent cells, however, leads to a tumor relapse under a condition of long-term androgen deprivation. Clinical trials suggest that intermittent androgen suppression (IAS) with alternating on- and off-treatment periods can delay the relapse when compared with continuous androgen suppression (CAS). In this paper, we propose a mathematical model for prostate tumor growth under IAS therapy. The model elucidates initial hormone sensitivity, an eventual relapse of a tumor under CAS therapy, and a delay of a relapse under IAS therapy, which are due to the coexistence of androgen-dependent cells, androgen-independent cells resulting from reversible changes by adaptation, and androgen-independent cells resulting from irreversible changes by genetic mutations. The model is formulated as a free boundary problem of partial differential equations that describe the evolution of populations of the abovementioned three types of cells during on-treatment periods and off-treatment periods. Moreover, the model can be transformed into a piecewise linear ordinary differential equation model by introducing three new volume variables, and the study of the resulting model may help to devise optimal IAS schedules.

Interocular suppression

Science.gov (United States)

Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes

2017-08-01

The objective of this work is to quantify the suppressive imbalance, based on the manipulation of ocular luminance, between a group of subjects with normal binocular vision and a group of subjects with amblyopia. The result reveals that there are statistically significant differences in interocular dominance between two groups, evidencing a greater suppressive imbalance in amblyopic subjects. The technique used, proved to be a simple, easy to apply and economic method, for quantified ocular dominance. It is presented as a technique with the potential to accompany subjects with a marked dominance in one of the eyes that makes fusion difficult.

RAF Suppression Synergizes with MEK Inhibition in KRAS Mutant Cancer Cells

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Simona Lamba

2014-09-01

Full Text Available KRAS is the most frequently mutated oncogene in human cancer, yet no therapies are available to treat KRAS mutant cancers. We used two independent reverse genetic approaches to identify components of the RAS-signaling pathways required for growth of KRAS mutant tumors. Small interfering RNA (siRNA screening of 37 KRAS mutant colorectal cancer cell lines showed that RAF1 suppression was synthetic lethal with MEK inhibition. An unbiased kinome short hairpin RNA (shRNA-based screen confirmed this synthetic lethal interaction in colorectal as well as in lung cancer cells bearing KRAS mutations. Compounds targeting RAF kinases can reverse resistance to the MEK inhibitor selumetinib. MEK inhibition induces RAS activation and BRAF-RAF1 dimerization and sustains MEK-ERK signaling, which is responsible for intrinsic resistance to selumetinib. Prolonged dual blockade of RAF and MEK leads to persistent ERK suppression and efficiently induces apoptosis. Our data underlie the relevance of developing combinatorial regimens of drugs targeting the RAF-MEK pathway in KRAS mutant tumors.

Volatile suppressing method for radioactive iodine

International Nuclear Information System (INIS)

Ohara, Atsushi; Haruguchi, Keiko.

1997-01-01

In the present invention, a metal plate is disposed above the pool water surface of a suppression chamber disposed to a reactor container in order to reduce evaporation of radioactive iodine released from a suppression pool. A metal plate is disposed above the pool water surface of the suppression chamber disposed to the reactor container. In addition, a metal plate is disposed around the space connecting a bent tube extending from a dry well to underwater of suppression pool water and a gas bent tube extending from the suppression chamber to an emergency gas processing system. Spray water is supplied for cooling the suppression chamber d as a means for cooling the metal plate. Then, among iodine released to the suppression chamber, elemental iodine liberated from the pool water is deposited on the surface of the metal plate, and the amount of iodine to be flown into and processed by an emergency gas processing system or a filter bent system can be reduced. (T.M.)

Zinc supplementation suppresses the progression of bile duct ligation-induced liver fibrosis in mice.

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Shi, Fang; Sheng, Qin; Xu, Xinhua; Huang, Wenli; Kang, Y James

2015-09-01

Metallothionein (MT) gene therapy leads to resolution of liver fibrosis in mouse model, in which the activation of collagenases is involved in the regression of liver fibrosis. MT plays a critical role in zinc sequestration in the liver suggesting its therapeutic effect would be mediated by zinc. The present study was undertaken to test the hypothesis that zinc supplementation suppresses liver fibrosis. Male Kunming mice subjected to bile duct ligation (BDL) resulted in liver fibrosis as assessed by increased α-smooth muscle actin (α-SMA) and collagen I production/deposition in the liver. Zinc supplementation was introduced 4 weeks after BDL surgery via intragastric administration once daily for 2 weeks resulting in a significant reduction in the collagen deposition in the liver and an increase in the survival rate. Furthermore, zinc suppressed gene expression of α-SMA and collagen I and enhanced the capacity of collagen degradation, as determined by the increased activity of total collagenases and elevated mRNA and protein levels of MMP13. Therefore, the results demonstrate that zinc supplementation suppresses BDL-induced liver fibrosis through both inhibiting collagen production and enhancing collagen degradation. © 2014 by the Society for Experimental Biology and Medicine.

The effects of nifekalant hydrochloride on the spatial dispersion of repolarization after direct current defibrillation in patients with oral amiodarone and β-blocker therapy

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Keiko Maeda

2014-06-01

Conclusions: NIF suppressed the deterioration of the SDR after ICD shock. This might be one of the mechanisms by which NIF suppresses recurrence of ventricular tachyarrhythmia just after ICD shock in patients with oral amiodarone and β-blocker therapy.

Suppression of in vitro cell-mediated lympholysis generation by alloactivated lymphocytes. Examination of radioresistant suppressive activity

International Nuclear Information System (INIS)

Orosz, C.G.; Ferguson, R.M.

1986-01-01

We investigated the radioresistant (1000 rads) suppression of CML generation mediated by alloactivated murine splenocytes. Suppressive cells were generated in MLCs by stimulation of (A X 6R)F1 splenocytes with irradiated C57BL/10 splenocytes. Suppressive cells could lyse targets bearing H-2b alloantigens, but would not lyse parental B10.T(6R) or B10.A targets. Suppressive activity was detected by including the alloactivated (A X 6R)F1 cells in B10.T(6R) anti-B10.A(1R) MLCs. Relative to the suppressive (A X 6R)F1 cells, the B10.A(1R) lymphocytes display both parental and suppressor-inducing alloantigens. In the absence of a suppressive population, B10.A(1R) stimulators cause B10.T(6R) splenocytes to generate cytolytic activity specific for both H-2Db (suppressor-inducing) and H-2Kk (suppressor-borne) target determinants. The irradiated, alloactivated (A X 6R)F1 cells decrease the H-2Db-specific CML generated in this system, thus mediating apparent antigen-specific suppression. However, cytolytic activity concomitantly generated in the same culture against the unrelated H-2Kk target determinants is similarly reduced by the (A X 6R)F1 cells. Thus, radioresistant suppression by alloactivated splenocytes is not necessarily antigen-specific. The irradiated (A X 6R)F1 cells would not suppress the generation of H-2Kk-specific CTL in B10.T(6R) anti-B10.A MLCs. Hence, the irradiated (A X 6R)F1 cells can impede CML generation against third-party alloantigens if, and only if, those alloantigens are coexpressed with suppressor-inducing alloantigens on the stimulator cells in suppressed MLCs. Similar results were also obtained using a different histoincompatible lymphocyte combination

Sub-optimal CD4 reconstitution despite viral suppression in an urban cohort on antiretroviral therapy (ART) in sub-Saharan Africa: frequency and clinical significance.

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Nakanjako, Damalie; Kiragga, Agnes; Ibrahim, Fowzia; Castelnuovo, Barbara; Kamya, Moses R; Easterbrook, Philippa J

2008-10-28

A proportion of individuals who start antiretroviral therapy (ART) fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV research cohort in Kampala, Uganda. We analyzed data from a prospective research cohort of 559 patients initiating ART between 04/04-04/05. We described the patterns of SO-CD4 both in terms of:- I) magnitude of CD4 cell increase (a CD4 count increase ART) and II) failure to achieve a CD4 cell count above 200 cells/microl at 6,12 and 24 months of ART. Using criteria I) we used logistic regression to determine the predictors of SO-CD4. We compared the cumulative risk of clinical events (death and/or recurrent or new AIDS-defining illnesses) among patients with and without SO-CD4. Of 559 patients initiating ART, 386 (69%) were female. Median (IQR) age and baseline CD4 counts were 38 yrs (33-44) and 98 cells/microl (21-163) respectively; 414 (74%) started a d4T-based regimen (D4T+3TC+NVP) and 145 (26%) a ZDV-based regimen (ZDV+3TC+EFV). After 6, 12 and 24 months of ART, 380 (68%), 339 (61%) and 309 (55%) had attained and sustained HIV-RNA viral suppression. Of these, 78 (21%), 151 (45%) and 166 (54%) respectively had SO-CD4 based on criteria I), and 165(43%), 143(42%) and 58(19%) respectively based on criteria II). With both criteria combined, 56 (15%) and 129 (38%) had SO-CD4 at 6 and 12 months respectively. A high proportion (82% and 58%) of those that had SO-CD4 at 6 months (using criteria I) maintained SO-CD4 at 12 and 24 months respectively. There were no statistically significant differences in the incidence of clinical events among patients with [19/100PYO (12-29)] and without SO-CD4 [23/100PYO (19-28)]. Using criteria I), the frequency of SO-CD4 was 21% at 6 months. Majority of patients with SO-CD4 at 6 months maintained SO-CD4 up to 2 years. We recommend studies of CD4 T

Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

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Theresa L. Whiteside

2016-10-01

Full Text Available Tumor-derived exosomes (TEX are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions. Although TEX can also stimulate immune activity, in the microenvironments dominated by the tumor, TEX tend to mediate immune suppression thus promoting tumor progression. The TEX content, in part resembling that of the parent cell, may serve as a source of cancer biomarkers. TEX also interfere with immune therapies. A better understanding of TEX and their contribution to cancer progression and cancer patients’ response to immune therapies represents a challenging new field of investigation.

Interferon-alpha suppressed granulocyte colony stimulating factor production is reversed by CL097, a TLR7/8 agonist.

LENUS (Irish Health Repository)

Tajuddin, Tariq

2012-02-01

BACKGROUND AND AIM: Neutropenia, a major side-effect of interferon-alpha (IFN-alpha) therapy can be effectively treated by the recombinant form of granulocyte colony stimulating factor (G-CSF), an important growth factor for neutrophils. We hypothesized that IFN-alpha might suppress G-CSF production by peripheral blood mononuclear cells (PBMCs), contributing to the development of neutropenia, and that a toll-like receptor (TLR) agonist might overcome this suppression. METHODS: Fifty-five patients who were receiving IFN-alpha\\/ribavirin combination therapy for chronic hepatitis C virus (HCV) infection were recruited. Absolute neutrophil counts (ANC), monocyte counts and treatment outcome data were recorded. G-CSF levels in the supernatants of PBMCs isolated from the patients and healthy controls were assessed by enzyme-linked immunosorbent assay following 18 h of culture in the absence or presence of IFN- alpha or the TLR7\\/8 agonist, CL097. RESULTS: Therapeutic IFN-alpha caused a significant reduction in neutrophil counts in all patients, with 15 patients requiring therapeutic G-CSF. The reduction in ANC over the course of IFN-alpha treatment was paralleled by a decrease in the ability of PBMCs to produce G-CSF. In vitro G-CSF production by PBMCs was suppressed in the presence of IFN-alpha; however, co-incubation with a TLR7\\/8 agonist significantly enhanced G-CSF secretion by cells obtained both from HCV patients and healthy controls. CONCLUSIONS: Suppressed G-CSF production in the presence of IFN-alpha may contribute to IFN-alpha-induced neutropenia. However, a TLR7\\/8 agonist elicits G-CSF secretion even in the presence of IFN-alpha, suggesting a possible therapeutic role for TLR agonists in treatment of IFN-alpha-induced neutropenia.

Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

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Szczygieł Dorota

2015-09-01

Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

Type I Collagen Synthesis Marker Procollagen I N-Terminal Peptide (PINP) in Prostate Cancer Patients Undergoing Intermittent Androgen Suppression

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Hamilton, Gerhard, E-mail: gerhard.hamilton@toc.lbg.ac.at; Olszewski-Hamilton, Ulrike [Ludwig Boltzmann Cluster of Translational of Oncology, Nussdorfer Strasse 64, Vienna A-1090 (Austria); Theyer, Gerhard [Hospital Kittsee, Kittsee A-2421, Burgenland (Austria)

2011-09-15

Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy.

Assessment of hair cortisol as a potential biomarker for possible adrenal suppression due to inhaled corticosteroid use in children with asthma: A retrospective observational study.

Science.gov (United States)

Smy, Laura; Shaw, Kaitlyn; Amstutz, Ursula; Staub, Michelle; Chaudhry, Shahnaz; Smith, Anne; Carleton, Bruce; Koren, Gideon

2018-06-01

Inhaled corticosteroids (ICS) are the recommended long-term control therapy for asthma in children. However, concern exists regarding potential adrenal suppression with chronic ICS use. Our pilot study reported that hair cortisol in children was 50% lower during ICS therapy than prior to therapy, suggestive of adrenal suppression. To evaluate hair cortisol concentration (HCC) as a potential biomarker for possible adrenal suppression from ICS use in children with asthma. A retrospective observational study was performed at asthma clinics in Vancouver, Winnipeg, and Toronto, Canada. Children (n = 586) were recruited from July 2012 to December 2014 inclusive of those without asthma, with asthma not using ICS, and with asthma using ICS. The most recent three-month HCC was measured by enzyme immunoassay and compared among the groups. Quantile regression analysis was performed to identify factors potentially affecting HCC. The median HCC was not significantly different among the children: No ICS (n = 47, 6.7 ng/g, interquartile range (IQR) 3.7-9.8 ng/g), ICS Treated (n = 360, 6.5 ng/g, IQR 3.8-14.3 ng/g), and Controls (n = 53, 5.8 ng/g, IQR 4.6-16.7 ng/g). 5.6% of the children using ICS had hair cortisol <2.0 ng/g compared to none in the control groups (P < .05, comparing ICS Treated (20/360) to all Controls combined (0/100)) and only half had been exposed to systemic corticosteroids. Age, sex, BMI, and intranasal corticosteroid use were significantly associated with HCC. Results suggest HCC may be a potential biomarker for adrenal suppression as a population of children using ICS with HCC < 2.0 ng/g was identified compared to none in the control groups. Further research is needed to determine if those children have or are at risk of adrenal suppression or insufficiency. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Novel form of miR-29b suppresses bleomycin-induced pulmonary fibrosis.

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Yuko Yamada

Full Text Available MicroRNA 29b (miR-29b replacement therapy is effective for suppressing fibrosis in a mouse model. However, to develop clinical applications for miRNA mimics, the side effects of nucleic acid drugs have to be addressed. In this study, we focused on miRNA mimics in order to develop therapies for idiopathic pulmonary fibrosis. We developed a single-stranded RNA, termed "miR-29b Psh-match," that has a unique structure to avoid problems associated with the therapeutic uses of miRNAs. A comparison of miR-29b Psh-match and double-stranded one, termed "miR-29b mimic" indicated that the single-stranded form was significantly effective towards fibrosis according to both in vivo and in vitro experiments. This novel form of miR-29b may become the foundation for developing an effective therapeutic drug for pulmonary fibrosis.

Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

International Nuclear Information System (INIS)

Balaha, Mohamed; Kandeel, Samah; Barakat, Waleed

2016-01-01

Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL 4 in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL 4 induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis in chronic

Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

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Balaha, Mohamed, E-mail: Mohamed.Balaha@Med.Tanta.Edu.Eg [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Kandeel, Samah [Histology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Barakat, Waleed [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt)

2016-11-15

Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL{sub 4} in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL{sub 4} induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis

Effect of modified fasting therapy on body weight, fat and muscle mass, and blood chemistry in patients with obesity.

Science.gov (United States)

Kim, Koh-Woon; Song, Mi-Yeon; Chung, Seok-Hee; Chung, Won-Seok

2016-02-01

The aim of this study was to investigate the effects and safety of modified fasting therapy using fermented medicinal herbs and exercise on body weight, fat and muscle mass, and blood chemistry in obese subjects. Twenty-six patients participated in a 14-day fast, during which they ingested a supplement made from fermented medicinal herbs and carbohydrates (intake: 400-600 kcal/d). The schedule included 7 prefasting relief days and 14 days of stepwise reintroduction of food. The patients also took part in an exercise program that incorporated Qigong, weight training, and walking exercises. The efficacy of treatments was observed by assessing body fat mass and muscle mass, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides in each study period. Specific symptoms or side effects were reported. Body weight and body fat mass both decreased significantly by (5.16 ± 0.95) and (3.89 ± 0.79) kg (both P fasting therapy using fermented medicinal herbs and exercise could be effective and safe on obese patients.

[Multilateral Strategies Utilizing Exosomes for Cancer Therapy].

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Nishida-Aoki, Nao; Ochiya, Takahiro

2017-05-01

Exosomes are nano-sized extracellular vesicles which transfer their components such as RNA, DNA, and proteins from one cell to another cell. The components are released to the cytoplasm of the recipient cells, having an effect on the cells. Cancerderived exosomes promote cancer progression, invasion, gain of drug resistance, and metastasis. Recently, according to their characteristics, it is expected to apply exosomes to cancer therapies, such as utilizing exosomes as drug delivery systems(DDS) for anticancer drugs and as cancer vaccines to enhance immunity to cancer cells. More, as the cancer-derived exosomes have cancer-promoting effects on multiple stages, inhibiting the function of the cancer-derived exosomes would be helpful to cancer therapies by suppressing cancer progression. DDS and cancer vaccines utilizing exosomes are now undergoing clinical studies, although DDS is suffering from loading efficiency. Treatments by inhibiting the functions of cancer-derived exosomes have still only few reports at experimental levels. Recently, we showed in a mouse model that disruption of cancer-derived exosomes by antibodies could suppress lung metastasis of the human breast cancer cells. Exosomes will provide us the multiple strategies to fight with cancer, which can be applied to cancers from many organs. It is important to confirm safety and overcome technical problems to bring exosomes in practical use.

Hepatic adverse events during highly active antiretroviral therapy containing nevirapine: a case report

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Yamazhan Tansu

2002-09-01

Full Text Available Abstract Background Hepatotoxicity is one of the most serious complications of highly active antiretroviral therapy (HAART. The aim of this report is to analyse an HIV infected patient on HAART including nevirapine and taking antidepressive agents, with acute toxic hepatitis. Case presentation A 39 year old patient diagnosed as HIV positive one month ago administered to the clinical ward of the Department of Infectious Diseases and Clinical Microbiology in Ege University Medical School with high fever, malaise, nausea, diarrheae and elevated liver enzymes (ALT 1558 U/L, AST 4288 U/L. He has been using HAART including zidovudine+lamivudine (2 × 1/day and nevirapine (2 × 200 mg/day, following dose escalation for 22 days, sertralin and diazepam for 12 days and lithium for 10 days. The patient was hospitalized. Antiretroviral and antidepressant treatments were stopped. The day after admission, his fever dropped and his symptoms improved. Clinical improvement continued on the following days. The patient was discharged upon his request on the 14th day of hospitalization. The liver function tests returned to normal levels in two weeks following discharge. Conclusion Close monitoring of liver enzymes during the first 12 weeks of nevirapine therapy is critical to prevent life threatening events.

Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy

International Nuclear Information System (INIS)

Pai, Howard Huaihan; Ludgate, Charles; Pickles, Tom; Paltiel, Chuck M.Sc.; Agranovich, Alex; Berthelet, Eric; Duncan, Graeme; Kim-Sing, Charmaine; Kwan, Winkle; Lim, Jan; Liu, Mitchell; Tyldesley, Scott

2006-01-01

Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival

Probing the hadronic phase with resonances of different lifetimes in Pb-Pb collisions with ALICE arXiv

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Agrawal, Neelima

The ALICE experiment has measured the production of a rich set of hadronic resonances, such as $\\rho(770)^{0}$, ${\\rm K}^{\\ast}(892)^{0}$, $\\phi$(1020), $\\Sigma^{\\pm}$(1385), $\\Lambda(1520)$ and $\\Xi^{\\ast 0}$ in pp, p-Pb and Pb-Pb collisions at various energies at the LHC. A comprehensive overview and the latest results are presented in this paper. Special focus is given to the role of hadronic resonances for the study of final-state effects in high-energy collisions. In particular, the measurement of resonance production in heavy-ion collisions has the capability to provide insight into the existence of a prolonged hadronic phase after hadronisation. The observation of the suppression of the production of $\\Lambda(1520)$ resonance in central Pb-Pb collisions at $\\sqrt{s_{\\rm NN}}$ = 2.76 TeV adds further support to the existence of such a dense hadronic phase, as already evidenced by the ratios ${\\rm K}^{\\ast}(892)^{0}$/${\\rm K}$ and $\\rho(770)^{0}$/$\\pi$.

Pressure suppression device

International Nuclear Information System (INIS)

Mizumachi, Wataru; Fukuda, Akira; Kitaguchi, Hidemi; Shimizu, Toshiaki.

1976-01-01

Object: To relieve and absorb impact wave vibrations caused by steam and non-condensed gases releasing into the pressure suppression chamber at the time of an accident. Structure: The reactor container is filled with inert gases. A safety valve attached main steam pipe is provided to permit the excessive steam to escape, the valve being communicated with the pressure suppression chamber through an exhaust pipe. In the pressure suppression chamber, a doughnut-like cylindrical outer wall is filled at its bottom with pool water to condense the high temperature vapor released through the exhaust pipe. A head portion of a vent tube which leads the exhaust pipe is positioned at the top, and a down comer and an exhaust vent tube are locked by means of steady rests. At the bottom is mounted a pressure adsorber device which adsorbs a pressure from the pool water. (Kamimura, M.)

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

International Nuclear Information System (INIS)

Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

2015-01-01

Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

Energy Technology Data Exchange (ETDEWEB)

Cho, Eunpi [University of Washington School of Medicine, Seattle, Washington (United States); Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Mostaghel, Elahe A. [Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A. [University of Washington School of Medicine, Seattle, Washington (United States); Kurland, Brenda F. [University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Marck, Brett T. [Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Matsumoto, Alvin M. [University of Washington School of Medicine, Seattle, Washington (United States); Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Dalkin, Bruce L. [University of Washington School of Medicine, Seattle, Washington (United States); Montgomery, R. Bruce, E-mail: rbmontgo@uw.edu [University of Washington School of Medicine, Seattle, Washington (United States)

2015-06-01

Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

Gene therapy for lung cancer.

Science.gov (United States)

Toloza, Eric M; Morse, Michael A; Lyerly, H Kim

2006-09-01

Lung cancer patients suffer a 15% overall survival despite advances in chemotherapy, radiation therapy, and surgery. This unacceptably low survival rate is due to the usual finding of advanced disease at diagnosis. However, multimodality strategies using conventional therapies only minimally improve survival rates even in early stages of lung cancer. Attempts to improve survival in advanced disease using various combinations of platinum-based chemotherapy have demonstrated that no regimen is superior, suggesting a therapeutic plateau and the need for novel, more specific, and less toxic therapeutic strategies. Over the past three decades, the genetic etiology of cancer has been gradually delineated, albeit not yet completely. Understanding the molecular events that occur during the multistep process of bronchogenic carcinogenesis may make these tasks more surmountable. During these same three decades, techniques have been developed which allow transfer of functional genes into mammalian cells. For example, blockade of activated tumor-promoting oncogenes or replacement of inactivated tumor-suppressing or apoptosis-promoting genes can be achieved by gene therapy. This article will discuss the therapeutic implications of these molecular changes associated with bronchogenic carcinomas and will then review the status of gene therapies for treatment of lung cancer. (c) 2006 Wiley-Liss, Inc.

Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

Directory of Open Access Journals (Sweden)

Amanda R Lorier

2010-01-01

Full Text Available Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity.A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons.The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

Energy Technology Data Exchange (ETDEWEB)

Niu, Mingshan [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Shen, Yangling; Xu, Xiaoyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Yao, Yao; Fu, Chunling [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Yan, Zhiling [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Wu, Qingyun [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Cao, Jiang; Sang, Wei [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Zeng, Lingyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Li, Zhenyu [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Liu, Xuejiao, E-mail: liuxuejiao0923@126.com [Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China); and others

2015-07-10

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

International Nuclear Information System (INIS)

Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao

2015-01-01

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys 38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy

A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

NARCIS (Netherlands)

Dybul, M; Nies-Kraske, E; Dewar, R; Maldarelli, F; Hallahan, CW; Daucher, M; Piscitelli, SC; Ehler, L; Weigand, A; Palmer, S; Metcalf, JA; Davey, RT; Kress, DMR; Powers, A; Beck, [No Value; Frenkel, L; Baseler, M; Coffin, J; Fauci, AS

2004-01-01

Background. We previously demonstrated that short-cycle structured intermittent therapy ( SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

Science.gov (United States)

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sodium fire suppression

International Nuclear Information System (INIS)

Malet, J.C.

1979-01-01

Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

Sodium fire suppression

Energy Technology Data Exchange (ETDEWEB)

Malet, J C [DSN/SESTR, Centre de Cadarache, Saint-Paul-lez-Durance (France)

1979-03-01

Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

NARCIS (Netherlands)

Graaf, Ymke Grete Leontien de

2008-01-01

Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy.

Assessment of hepatitis B immunization status after antineoplastic therapy in children with cancer

OpenAIRE

Karaman, Serap; Vural, Sema; Yildirmak, Yildiz; Urganci, Nafiye; Usta, Merve

2011-01-01

BACKGROUND AND OBJECTIVES: Hepatitis B is a disease that is preventable with vaccination. Antibody levels after vaccination may be affected by suppression of the immune system due to cancer therapy. Children with cancer have a high risk of hepatitis B virus (HBV) infection. We aimed to assess the pretreatment immunization status against HBV infection and the rate of continuity of immunization after therapy in children with cancer. DESIGN AND SETTING: Retrospective case review of patients trea...

Comparative Metatranscriptomics of Wheat Rhizosphere Microbiomes in Disease Suppressive and Non-suppressive Soils for Rhizoctonia solani AG8

Directory of Open Access Journals (Sweden)

Helen L. Hayden

2018-05-01

Full Text Available The soilborne fungus Rhizoctonia solani anastomosis group (AG 8 is a major pathogen of grain crops resulting in substantial production losses. In the absence of resistant cultivars of wheat or barley, a sustainable and enduring method for disease control may lie in the enhancement of biological disease suppression. Evidence of effective biological control of R. solani AG8 through disease suppression has been well documented at our study site in Avon, South Australia. A comparative metatranscriptomic approach was applied to assess the taxonomic and functional characteristics of the rhizosphere microbiome of wheat plants grown in adjacent fields which are suppressive and non-suppressive to the plant pathogen R. solani AG8. Analysis of 12 rhizosphere metatranscriptomes (six per field was undertaken using two bioinformatic approaches involving unassembled and assembled reads. Differential expression analysis showed the dominant taxa in the rhizosphere based on mRNA annotation were Arthrobacter spp. and Pseudomonas spp. for non-suppressive samples and Stenotrophomonas spp. and Buttiauxella spp. for the suppressive samples. The assembled metatranscriptome analysis identified more differentially expressed genes than the unassembled analysis in the comparison of suppressive and non-suppressive samples. Suppressive samples showed greater expression of a polyketide cyclase, a terpenoid biosynthesis backbone gene (dxs and many cold shock proteins (csp. Non-suppressive samples were characterised by greater expression of antibiotic genes such as non-heme chloroperoxidase (cpo which is involved in pyrrolnitrin synthesis, and phenazine biosynthesis family protein F (phzF and its transcriptional activator protein (phzR. A large number of genes involved in detoxifying reactive oxygen species (ROS and superoxide radicals (sod, cat, ahp, bcp, gpx1, trx were also expressed in the non-suppressive rhizosphere samples most likely in response to the infection of wheat

In-Flight Suppressant Deployment Temperatures

National Research Council Canada - National Science Library

Bein, Donald

2006-01-01

.... An assessment is made of the model output versus some aircraft measurement data, fire suppressant boiling point criterion, as well as the history of altitude/temperature at which fire suppressants have been deployed...

Clinical characteristics predict benefits from eptifibatide therapy during coronary stenting: insights from the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial.

Science.gov (United States)

Puma, Joseph A; Banko, Lesan T; Pieper, Karen S; Sacchi, Terrence J; O'Shea, J Conor; Dery, Jean Pierre; Tcheng, James E

2006-02-21

In order to determine a differential benefit from treatment, we compared the long-term outcome of high-risk versus low-risk patients and evaluated survival free from death or myocardial infarction at one year. Newer anticoagulant strategies during percutaneous coronary intervention have necessitated a reanalysis of the role of intravenous GP IIb/IIIa inhibitors. The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy trial randomized 2,064 patients undergoing nonurgent coronary stent implantation to eptifibatide or placebo. High-risk characteristics were defined as age >75 years, diabetes, elevated cardiac markers, ST-segment elevation myocardial infarction within 7 days, or unstable angina within 48 h of randomization. Age <5 years, absence of diabetes, and any other reason for admission were considered low risk characterstics. There were 1,018 patients in the high-risk group (50.8% eptifibatide, 49.2% placebo) and 1,045 patients in the low-risk group (50.0% eptifibatide, 50.0% placebo). Baseline demographics were similar in both groups except for more hypertension (63% vs. 55%, respectively), peripheral vascular disease (8.2% vs. 5.2%, respectively), prior stroke (5.5% vs. 3.2%, respectively), and female gender (33% vs. 22%, respectively) in the high-risk than the low-risk group. At one year, the composite end point of death or myocardial infarction occurred in 15.89% of placebo patients and 7.99% of eptifibatide patients in the high-risk group and 9.02% of the placebo and 8.11% of eptifibatide patients in the low-risk group. Although eptifibatide treatment improved outcomes for all patients, preprocedural clinical characteristics can define a subgroup of patients who may derive greatest benefit from its use during coronary stent placement.

Monitoring the autonomic nervous activity as the objective evaluation of music therapy for severely and multiply disabled children.

Science.gov (United States)

Orita, Makiko; Hayashida, Naomi; Shinkawa, Tetsuko; Kudo, Takashi; Koga, Mikitoshi; Togo, Michita; Katayama, Sotetsu; Hiramatsu, Kozaburo; Mori, Shunsuke; Takamura, Noboru

2012-07-01

Severely and multiply disabled children (SMDC) are frequently affected in more than one area of development, resulting in multiple disabilities. The aim of the study was to evaluate the efficacy of music therapy in SMDC using monitoring changes in the autonomic nervous system, by the frequency domain analysis of heart rate variability. We studied six patients with SMDC (3 patients with cerebral palsy, 1 patient with posttraumatic syndrome after head injury, 1 patient with herpes encephalitis sequelae, and 1 patient with Lennox-Gastaut syndrome characterized by frequent seizures, developmental delay and psychological and behavioral problems), aged 18-26 (mean 22.5 ± 3.5). By frequency domain method using electrocardiography, we measured the high frequency (HF; with a frequency ranging from 0.15 to 0.4 Hz), which represents parasympathetic activity, the low frequency/high frequency ratio, which represents sympathetic activity between the sympathetic and parasympathetic activities, and heart rate. A music therapist performed therapy to all patients through the piano playing for 50 min. We monitored each study participant for 150 min before therapy, 50 min during therapy, and 10 min after therapy. Interestingly, four of 6 patients showed significantly lower HF components during music therapy than before therapy, suggesting that these four patients might react to music therapy through the suppression of parasympathetic nervous activities. Thus, music therapy can suppress parasympathetic nervous activities in some patients with SMDC. The monitoring changes in the autonomic nervous activities could be a powerful tool for the objective evaluation of music therapy in patients with SMDC.

The suppression of manganese superoxide dismutase decreased the survival of human glioblastoma multiforme T98G cells

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Novi S. Hardiany

2017-05-01

Full Text Available Background: Glioblastoma multiforme (GBM is a primary malignant brain tumor which has poor prognosis. High incidence of oxidative stress-based therapy resistance could be related to the high antioxidant status of GBM cells. Our previous study has reported that manganese superoxide dismutase (MnSOD antioxidant expression was significantly higher in high grade glioma than in low grade. The aim of this study was to analyze the impact of MnSOD suppression toward GBM cell survival.Methods: This study is an experimental study using human glioblastoma multiforme T98G cell line. Suppression of MnSOD expression was performed using in vitro transfection MnSOD-siRNA. The MnSOD expression was analyzed by measuring the mRNA using real time RT-PCR, protein using ELISA technique, and specific activity of enzyme using inhibition of xantine oxidase. Concentration of reactive oxygen species (ROS intracellular was determined by measuring superoxide radical and hydrogen peroxide. Cell survival was analyzed by measuring viability, proliferation, and cell apoptosis.Results: In vitro transfection of MnSOD-siRNA suppressed the mRNA, protein, and specific activity of MnSOD. This treatment significantly increased the concentration of superoxide radical; however, it did not influence the concentration of hydrogen peroxide. Moreover, viability MnSOD-suppressing cell significantly decreased, accompanied by increase of cell apoptosis without affecting cell proliferation.Conclusion: The suppression of MnSOD expression leads to decrease glioblastoma multiforme cell survival, which was associated to the increase of cell apoptotic.

Valor preditivo de marcadores séricos de fibrose hepática em pacientes portadores de hepatite crônica viral C Predictive value of serum markers of hepatic fibrosis in patients with chronic hepatitis C

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Leila Maria Soares Tojal de Barros Lima

2008-06-01

Full Text Available INTRODUÇÃO: Os marcadores séricos têm sido empregados na avaliação da fibrose hepática em pacientes portadores de hepatite crônica C (HCC. OBJETIVOS: Avaliar a capacidade do índice aspartato aminotransferase (AST/alanina aminotransferase (ALT, dos níveis séricos de gama-glutamiltransferase (GGT, contagem de plaquetas, do índice AST/plaquetas (APRI e do ácido hialurônico (AH em predizer a intensidade da fibrose hepática na HCC e a variação desses marcadores após tratamento com interferon. PACIENTES E MÉTODOS: Em 72 pacientes portadores de hepatite C determinamos no soro o índice AST/ALT, GGT, plaquetas, índice APRI (obtido pelo quociente AST/plaquetas e o AH, que foram comparados ao estadiamento histológico, segundo os critérios de METAVIR. Receberam tratamento com interferon e ribavirina 65 pacientes. Os indivíduos que concluíram o tratamento (n = 33 realizaram nova dosagem dos marcadores séricos de fibrose para comparar com os níveis pré-tratamento. RESULTADOS: Observamos que a GGT, a contagem de plaquetas, o índice APRI e o AH se correlacionaram com estádio de doença hepática (p INTRODUCTION: Serum markers have been used in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC. AIMS: We evaluated the capacity of aspartate aminotransferase (AST/alanine aminotransferase (ALT ratio, gama-glutamyltransferase (GGT levels, platelet count, the AST to platelet ratio index (APRI and serum hyaluronic acid (HA to predict the intensity of hepatic fibrosis in patients with CHC and the variation of these markers after therapy with interferon. PATIENTS AND METHODS: In 72 patients with hepatitis C, AST/ALT ratio, GGT levels, platelet count, the APRI index (calculated as the ratio of AST to platelets and serum HA concentration were determined and compared to histological staging according to the scoring system of METAVIR. Sixty-five patients received interferon and ribavirin therapy. The individuals that

Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer.

Science.gov (United States)

Santagata, Sara; Napolitano, Maria; D'Alterio, Crescenzo; Desicato, Sonia; Maro, Salvatore Di; Marinelli, Luciana; Fragale, Alessandra; Buoncervello, Maria; Persico, Francesco; Gabriele, Lucia; Novellino, Ettore; Longo, Nicola; Pignata, Sandro; Perdonà, Sisto; Scala, Stefania

2017-09-29

With the intent to identify biomarkers in renal cell carcinoma (RCC) the functional status of T-regulatory cells (Tregs) was investigated in primary RCC. Tregs were isolated from tumoral-(TT), peritumoral tissue-(PT) and peripheral blood-(PB) of 42 primary RCC patients and function evaluated through effector T cells (Teff) proliferation, cytokines release and demethylation of Treg Specific Region (TSDR). The highest value of Tregs was detected in TT with the uppermost amount of effector-Tregs-(CD4 + CD25 hi FOXP3 hi CD45RA - ). PB-RCC Tregs efficiently suppress Teff proliferation compared to healthy donor (HD)-Tregs and, at the intrapatient evaluation, TT-derived Tregs were the most suppressive. Higher demethylation TSDR was detected in TT- and PB-RCC Tregs vs HD-Tregs ( P <0,001). CXCR4 is highly expressed on Tregs, thus we wished to modulate Tregs function through CXCR4 inhibition. CXCR4 antagonism, elicited by a new peptidic antagonist, Peptide-R29, efficiently reversed Tregs suppression of Teff proliferation. Thus Tregs functional evaluation precisely reflects Tregs status and may be a reliable biomarker of tumoral immune response. In addition, treatment with CXCR4 antagonist, impairing Tregs function, could improve the anticancer immune response, in combination with conventional therapy and/or immunotherapy such as checkpoints inhibitors.

Suppression effects on musical and verbal memory.

Science.gov (United States)

Schendel, Zachary A; Palmer, Caroline

2007-06-01

Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues.

Modelling Ebola virus dynamics: Implications for therapy.

Science.gov (United States)

Martyushev, Alexey; Nakaoka, Shinji; Sato, Kei; Noda, Takeshi; Iwami, Shingo

2016-11-01

Ebola virus (EBOV) causes a severe, often fatal Ebola virus disease (EVD), for which no approved antivirals exist. Recently, some promising anti-EBOV drugs, which are experimentally potent in animal models, have been developed. However, because the quantitative dynamics of EBOV replication in humans is uncertain, it remains unclear how much antiviral suppression of viral replication affects EVD outcome in patients. Here, we developed a novel mathematical model to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and evaluated the effects of different antivirals. We found that nucleoside analogue- and siRNA-based therapies are effective if a therapy with a >50% inhibition rate is initiated within a few days post-symptom-onset. In contrast, antibody-based therapy requires not only a higher inhibition rate but also an earlier administration, especially for otherwise fatal cases. Our results demonstrate that an appropriate choice of EBOV-specific drugs is required for effective EVD treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Suppress to feel and remember less: Neural correlates of explicit and implicit emotional suppression on perception and memory.

Science.gov (United States)

Katsumi, Yuta; Dolcos, Sanda

2018-02-09

Available evidence suggests that emotion regulation can modulate both immediate (emotional experience) and long-term (episodic memory) effects of emotion, and that both explicit and implicit forms may be effective. However, neural mechanisms by which explicit and implicit emotional suppression affect these phenomena remain unclear, particularly regarding their effects on memory. In this study, participants rated the emotional content of negative and neutral images, following explicit (verbal instructions) or implicit (priming) induction of emotional suppression goals, during functional magnetic resonance imaging. Participants' memory for the images was tested one week later. Behaviorally, explicit suppression reduced emotional ratings of negative images, whereas both explicit and implicit suppression reduced subsequent memory. At the neural level, the engagement of explicit suppression was uniquely associated with decreased activity in the amygdala (AMY), during emotional ratings, and in the AMY and inferior frontal gyrus (IFG), during successful encoding. Although both explicit and implicit suppression diminished functional connectivity between these regions and the hippocampus (HC) linked to successful encoding, explicit suppression was uniquely associated with interference with AMY-HC interactions, which no longer predicted subsequent memory for the explicitly-suppressed items. Overall, these findings advance our understanding of the common and dissociable mechanisms of explicit and implicit emotional suppression on perception and memory, and suggest their impact on both bottom-up and top-down mechanisms involved in emotion-cognition interactions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pharmacotherapy for uveitis: current management and emerging therapy

Science.gov (United States)

Barry, Robert J; Nguyen, Quan Dong; Lee, Richard W; Murray, Philip I; Denniston, Alastair K

2014-01-01

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual function for patients with the minimum possible side effects. PMID:25284976

Efeitos da farinha de folhas de mandioca sobre a atividade das enzimas AST, ALT, FA e lipídios hepáticos de ratos Wistar Effects of cassava leaves flour on the AST, ALT, ALP enzymes activity and hepatic lipids of Wistar rats

Directory of Open Access Journals (Sweden)

Daniela Séfora de Melo

2008-12-01

Full Text Available Folhas de mandioca possuem substâncias como ligninas e saponinas que podem apresentar efeito hipolipidêmico. Todavia, um estudo recente relatou aumento no peso do fígado de ratos alimentados com dietas contendo farinha de folhas de mandioca (FFM - Manihot esculenta Crantz cv. Cacao, tornando-se necessário um estudo mais aprofundado dos efeitos desta farinha sobre os parâmetros hepáticos. Para este estudo, um ensaio biológico com 32 ratos machos Wistar foi conduzido por um período de 7 semanas, sendo os tratamentos: dieta controle e dietas contendo 5, 10 e 15% de FFM. As dietas contendo FFM não apresentaram efeitos sobre as atividades das enzimas Aspartato Aminotransferase (AST e Fosfatase Alcalina (FA, mas aumentaram significativamente a atividade da enzima alanina aminotransferase (ALT. O estudo histopatológico revelou vacuolização do citoplasma dos hepatócitos para todos os grupos. No entanto, a freqüência de animais com vacuolização acentuada foi superior nos grupos que receberam dietas com FFM, apresentando também maiores teores de lipídios e colesterol total hepáticos e maior relação peso fígado/peso corporal. Estes resultados indicam que os antinutrientes presentes nas folhas de mandioca, como taninos, cianeto e saponinas, podem ser responsáveis pela redução da função hepática nos animais alimentados com FFM.Cassava leaves contain substances such as lignins and saponins that can present the hypolipidemic effect. However, a recent study has reported an increase in liver weight of rats fed diet containing cassava leaves flour (CLF - Manihot esculenta Crantz cv. Cacao. Thus, a further study of the effect of this flour on the hepatic parameters is necessary. For the development of this study, a biological assay with 32 male Wistar rats was conducted for a period of 7 weeks with the following treatments: control diet and diets containing 5, 10, and 15% of CLF. The diets containing CLF showed no effects on the

Biomarkers of Oxidative Stress and Personalized Treatment of Pulmonary Tuberculosis: Emerging Role of Gamma-Glutamyltransferase

Directory of Open Access Journals (Sweden)

Etienne Mokondjimobe

2012-01-01

Full Text Available Background. The objectives were (i to evaluate the impact of acute pulmonary tuberculosis (PTB and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of 34.7±5.8 years with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n=1 developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0–day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR.

Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

Energy Technology Data Exchange (ETDEWEB)

Nichols, R. Charles, E-mail: rnichols@floridaproton.org [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Williams, Christopher R.; Costa, Joseph A. [Division of Urology, University of Florida Shands Hospital, Jacksonville, FL (United States); Mendenhall, Nancy P. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

2012-03-01

Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

International Nuclear Information System (INIS)

Nichols, R. Charles; Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng; Williams, Christopher R.; Costa, Joseph A.; Mendenhall, Nancy P.

2012-01-01

Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART: a cross-sectional study.

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Johannes S Gach

Full Text Available The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA 10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02 and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA 5 years, p = 0.08. All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.

Mdm2 Deficiency Suppresses MYCN-Driven Neuroblastoma Tumorigenesis In Vivo

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Zaowen Chen

2009-08-01

Full Text Available Neuroblastoma is derived from neural crest precursor components of the peripheral sympathetic nervous system and accounts for more than 15% of all pediatric cancer deaths. A clearer understanding of the molecular basis of neuroblastoma is required for novel therapeutic approaches to improve morbidity and mortality. Neuroblastoma is uniformly p53 wild type at diagnosis and must overcome p53-mediated tumor suppression during pathogenesis. Amplification of the MYCN oncogene correlates with the most clinically aggressive form of the cancer, and MDM2, a primary inhibitor of the p53 tumor suppressor, is a direct transcriptional target of, and positively regulated by, both MYCN and MYCC. We hypothesize that MDM2 contributes to MYCN-driven tumorigenesis helping to ameliorate p53-dependent apoptotic oncogenic stress during tumor initiation and progression. To study the interaction of MYCN and MDM2, we generated an Mdm2 haploinsufficient transgenic animal model of neuroblastoma. In Mdm2+/-MYCN transgenics, tumor latency and animal survival are remarkably extended, whereas tumor incidence and growth are reduced. Analysis of the Mdm2/p53 pathway reveals remarkable p53 stabilization counterbalanced by epigenetic silencing of the p19Arf gene in the Mdm2 haploinsufficient tumors. In human neuroblastoma xenograft models, conditional small interfering RNA-mediated knockdown of MDM2 in cells expressing wild-type p53 dramatically suppresses tumor growth in a p53-dependent manner. In summary, we provided evidence for a crucial role for direct inhibition of p53 by MDM2 and suppression of the p19ARF/p53 axis in neuroblastoma tumorigenesis, supporting the development of therapies targeting these pathways.

Probiotics-mediated suppression of cancer.

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So, Stephanie S Y; Wan, Murphy L Y; El-Nezami, Hani

2017-01-01

Probiotics can be used as an adjuvant for cancer prevention or/and treatment through their abilities to modulate intestinal microbiota and host immune response. Although most of the recent reviews have focused on the potential role of probiotics against colon cancer, only few of them include the probiotic effect on extraintestinal cancers. The present review covers the most important findings from the literature published during the past 20 months (from January 2015 to August 2016) regarding the probiotics-mediated suppression of both gastrointestinal and extraintestinal cancers and the underlying mechanisms. A comprehensive literature search in Pubmed, Science direct and Google scholar databases was conducted to locate all relevant articles that investigated the effect of probiotics on prevention/treatment of both gastrointestinal and extraintestinal cancers. Different mechanisms for the beneficial effects of probiotics against cancer were also discussed, mainly via modulation of gut microbiota which thereby influences host metabolism and immunity. Despite laboratory-based studies having demonstrated encouraging outcomes that probiotics possess antitumor effects, the benefits should not be exaggerated before we get more results from human clinical trials. These are very important before the medical community can accept the use of probiotics as an alternative therapy for cancer control.

Electrical Storm: Incidence, Prognosis and Therapy.

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Sagone, Antonio

2015-12-01

The term "electrical storm" indicates a life-threatening clinical condition characterized by the recurrence of hemodynamically unstable ventricular tachycardia and/or ventricular fibrillation, in particular in patients with ICD implanted for primary or secondary prevention. Although there isn't a shared definition of electrical storm, nowadays the most accepted definition refers to three or more separate arrhythmia episodes leading to ICD therapies including antitachycardia pacing or shock occurring over a single 24 hours' time period. Clinical presentation can be dramatic and triggering mechanism are not clear at all yet, but electrical storm is associated with high mortality rates and low patients quality of life, both in the acute phase and in the long term. The first line therapy is based on antiarrhythmic drugs to suppress electrical storm, but in refractory patients, interventions such as catheter ablation or in some cases surgical cardiac sympathetic denervation might be helpful. Anyhow, earlier interventional management can lead to better outcomes than persisting with antiarrhythmic pharmacologic therapy and, when available, an early interventional approach should be preferred.

Bone Marrow Gene Therapy for HIV/AIDS

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Elena Herrera-Carrillo

2015-07-01

Full Text Available Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS caused by human immunodeficiency virus (HIV. This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described.

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

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Christian Bressy

2017-06-01

Full Text Available Oncolytic virus (OV therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53 or another p53 family member (TP63 or TP73 were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

Suppression of choriocarcinoma invasion and metastasis following blockade of BDNF/TrkB signaling

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Kawamura, Kazuhiro; Kawamura, Nanami; Okamoto, Naoki; Manabe, Motomu

2013-01-01

Brain-derived neurotrophic factor (BDNF) acts through its cognate receptor tyrosine kinase-B (TrkB) to regulate diverse physiological functions in reproductive and other tissues. In normal and malignant trophoblastic cells, the BDNF/TrkB signaling promotes cell growth. Due to the highly malignant nature of choriocarcinoma, we investigated possible involvement of this system in choriocarcinoma cell invasion and metastasis. We demonstrated that treatment of cultured choriocarcinoma cells, known to express both BDNF and TrkB, with a soluble TrkB ectodomain or a Trk receptor inhibitor K252a suppressed cell invasion accompanied with decreased expression of matrix metalloproteinase-2, a cell invasion marker. In vivo studies using a tumor xenograft model in athymic nude mice further showed inhibition of cell invasion from tumors to surrounding tissues following the suppression of endogenous TrkB signaling. For an in vivo model of choriocarcinoma metastasis, we performed intravenous injections of JAR cells expressing firefly luciferase into severe combined immunodeficiency (SCID) mice. Treatment with K252a inhibited metastasis of tumors to distant organs. In vivo K252a treatment also suppressed metastatic tumor growth as reflected by decreased cell proliferation and increased apoptosis and caspases-3/7 activities, together with reduced tissue levels of a tumor marker, human chorionic gonadotropin-β. In vivo suppression of TrkB signaling also led to decreased expression of angiogenic markers in metastatic tumor, including cluster of differentiation 31 and vascular endothelial growth factor A. Our findings suggested essential autocrine/paracrine roles of the BDNF/TrkB signaling system in choriocarcinoma invasion and metastasis. Inhibition of this signaling could serve as the basis to develop a novel therapy for patients with choriocarcinoma

Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing.

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Datsen George Wei

2014-04-01

Full Text Available Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD, a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM compared with vorinostat (VOR; EC50 = 3,950 nM and other histone deacetylase (HDAC inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM. The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART, a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART.

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-week results of a randomized trial.

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Barbara Rossetti

Full Text Available Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption per protocol at week 48.Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm or continue current ART (continuation arm.In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm. The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005. The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030. At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm.Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

The impact of nevirapine- versus protease inhibitor-based regimens on virological markers of HIV-1 persistence during seemingly suppressive ART.

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Kiselinova, Maja; Anna, Maria; Malatinkova, Eva; Vervish, Karen; Beloukas, Apostolos; Messiaen, Peter; Bonczkowski, Pawel; Trypsteen, Wim; Callens, Steven; Verhofstede, Chris; De Spiegelaere, Ward; Vandekerckhove, Linos

2014-01-01

The source and significance of residual plasma HIV-1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)-based regimens achieve a greater HIV-1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP- vs PI-based ART on the virological markers of HIV persistence in peripheral blood. The study population comprised 161 HIV-1 infected patients receiving either NVP-based (n=81) or PI-based (n=80) ART and showing a HIV-1 RNA load stably suppressed ART, with median (IQR) levels of 5 (3-6) and 5 (3-8) copies/mL, respectively. HIV-1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV-1 DNA levels were median 282 (120-484) and 213 (87-494) copies/106 PBMCs in the two groups respectively, and were lowest (ART HIV-1 RNA load (p=0.0001). In this comprehensive characterization of patients on long-term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP-based over PI-based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV-1 expression as an important cohort for future HIV cure studies.

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

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Hsin-Hung Li

2015-10-01

Full Text Available In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression, the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature and divisive normalization contribute to interocular suppression.

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

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Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

2015-10-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

Psychopathology and Thought Suppression: A Quantitative Review

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Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

2012-01-01

Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference

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Tavangar Seyed

2007-06-01

Full Text Available Abstract Background The diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach. Methods The study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses. Results There are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6th month after the start of suppressive L-thyroxine therapy in post-menopausal women. Conclusion It seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.

The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis.

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Sahin, Ozlem; Ziaei, Alireza

2014-07-01

This study was designed to investigate whether the antiinflammatory and antiproliferative activity of oral and intravitreal methotrexate (MTX) suppresses intraocular inflammation in patients with presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis. Interventional prospective study including three cases with presumed latent syphilitic uveitis treated with intravenous penicillin and oral MTX, and two cases with presumed tuberculosis-related uveitis treated with standard antituberculosis therapy and intravitreal MTX injections. Treatment efficacy of all cases was assessed by best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography. Four eyes of 3 patients with presumed latent syphilitic uveitis had improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema in 6 months with oral MTX therapy. No recurrence of intraocular inflammation was observed in 6 months to 18 months of follow-up period after cessation of MTX. Two eyes of two patients with presumed tuberculosis-related uveitis showed improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema after intravitreal injections of MTX. No recurrence of intraocular inflammation was observed in 6 months to 8 months of follow-up period after cessation of antituberculous therapy. For the first time in the treatment of presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis, we believe that MTX might have an adjunctive role to suppress intraocular inflammation, reduce uveitic macular edema, and prevent the recurrences of the diseases.

In the suppression of regge cut contributions

International Nuclear Information System (INIS)

Chia, S.P.

1975-07-01

It is shown that contributions of reggeon-pomeron cuts are suppressed in amplitudes with opposite natural to the reggeon. This suppression grows logarithmically with energy. The suppression in the πP cut is, however, found to be weak. Consequence on conspiracy is discussed

Compton suppression gamma ray spectrometry

International Nuclear Information System (INIS)

Landsberger, S.; Iskander, F.Y.; Niset, M.; Heydorn, K.

2002-01-01

In the past decade there have been many studies to use Compton suppression methods in routine neutron activation analysis as well as in the traditional role of low level gamma ray counting of environmental samples. On a separate path there have been many new PC based software packages that have been developed to enhance photopeak fitting. Although the newer PC based algorithms have had significant improvements, they still suffer from being effectively used in weak gamma ray lines in natural samples or in neutron activated samples that have very high Compton backgrounds. We have completed a series of experiments to show the usefulness of Compton suppression. As well we have shown the pitfalls when using Compton suppression methods for high counting deadtimes as in the case of neutron activated samples. We have also investigated if counting statistics are the same both suppressed and normal modes. Results are presented in four separate experiments. (author)

Development of Viral Vectors for Gene Therapy for Chronic Pain

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Yu Huang

2011-01-01

Full Text Available Chronic pain is a major health concern that affects millions of people. There are no adequate long-term therapies for chronic pain sufferers, leading to significant cost for both society and the individual. The most commonly used therapy for chronic pain is the application of opioid analgesics and nonsteroidal anti-inflammatory drugs, but these drugs can lead to addiction and may cause side effects. Further studies of the mechanisms of chronic pain have opened the way for development of new treatment strategies, one of which is gene therapy. The key to gene therapy is selecting safe and highly efficient gene delivery systems that can deliver therapeutic genes to overexpress or suppress relevant targets in specific cell types. Here we review several promising viral vectors that could be applied in gene transfer for the treatment of chronic pain and further discuss the possible mechanisms of genes of interest that could be delivered with viral vectors for the treatment of chronic pain.

Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: a case report

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Zarallo Luis

2007-05-01

Full Text Available Abstract Background Fusarium spp. is being isolated with increasing frequency as a pathogen in oncohematologic patients. Caspofungin and amphotericin B have been reported to have synergistic activity against Fusarium spp. Case presentation We herein report a case of disseminated fusariosis diagnosed by chest CT scan and positive blood cultures to Fusarium spp. Because the patient's clinical condition deteriorated, CRP levels increased, and blood cultures continued to yield Fusarium spp. despite liposomal amphotericin B monotherapy up to 5 mg/kg daily, treatment with caspofungin was added. Within 2 weeks of onset of combined antifungal therapy, the chest CT scan demonstrated a progressive resolution of the pulmonary lesions. Upon discontinuation of intravenous antifungals, the patient received suppressive therapy with oral voriconazole. Three months later, a chest CT scan showed no abnormalities. Twenty-five months after discontinuation of all antifungal therapy, the patient remains in complete remission of her neoplastic disease with no signs of clinical activity of the Fusarium infection. Conclusion This is the first description of successful treatment of disseminated fusariosis in a pediatric patient with acute lymphoblastic leukemia with caspofungin and amphotericin B followed by oral suppressive therapy with voriconazole.

Gene therapy in animal models of autosomal dominant retinitis pigmentosa

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Rossmiller, Brian; Mao, Haoyu

2012-01-01

Gene therapy for dominantly inherited genetic disease is more difficult than gene-based therapy for recessive disorders, which can be treated with gene supplementation. Treatment of dominant disease may require gene supplementation partnered with suppression of the expression of the mutant gene either at the DNA level, by gene repair, or at the RNA level by RNA interference or transcriptional repression. In this review, we examine some of the gene delivery approaches used to treat animal models of autosomal dominant retinitis pigmentosa, focusing on those models associated with mutations in the gene for rhodopsin. We conclude that combinatorial approaches have the greatest promise for success. PMID:23077406

[Significance of emotion-focused concepts to cognitive-behavioral therapy].

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Lammers, C-H

2006-09-01

Emotions are the central process of motivation and play a key role in adaptive behavior in humans. Although cognitive-behavioral therapy stresses the importance of changing both cognition and behavior, there is growing emphasis on direct therapeutic work on emotions and emotional processing, as problematic emotional processes are at the core of nearly all psychic disorders. This type of work is the goal of emotion-focused psychotherapy, which centers on direct change of problematic emotions, especially those which are usually suppressed resp. overregulated by the patient. This paper examines the basic phobic/emotional conflict, the problematic emotional processes arising from this conflict, and the importance to cognitive-behavioral therapy of their potentially integrative role.

Baicalein suppresses the androgen receptor (AR)-mediated prostate cancer progression via inhibiting the AR N-C dimerization and AR-coactivators interaction.

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Xu, Defeng; Chen, Qiulu; Liu, Yalin; Wen, Xingqiao

2017-12-01

Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression. PCa cells including LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with baicalein and luciferase assay was used to evaluate their effect on the AR transactivation. Cell growth and IC 50 were determined by MTT assay after 48 hrs treatment. RT-PCR was used to evaluate the mRNA levels of AR target genes including PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR and PSA protein expression. The natural product of baicalein can selectively inhibit AR transactivation with little effect on the other nuclear receptors, including ERα, and GR. At a low concentration, 2.5 μM of baicalein effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Mechanism dissection suggest that baicalein can suppress AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive LNCaP cells and castration resistant CWR22Rv1 cells, that may involve the inhibiting the AR N/C dimerization and AR-coactivators interaction. Baicalein may be developed as an effective anti-AR therapy via its ability to inhibit AR transactivation and AR-mediated PCa cell growth.

Poppers: more evidence of suppressed immunity.

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James, J S

1999-08-20

Evidence from studies in mice shows that exposure to isobutyl nitrite suppresses the immune system. This immune suppression allows for bacterial growth in the lungs and livers of infected mice and can inhibit the ability of mediastinal lymph nodes to respond to antigen-specific stimulation. The mechanism for immune suppression may be a reduction in CD4+ and CD8+ T cell populations in the mediastinal lymph nodes following pulmonary infection with Listeria monocytogenes.

Immunostimulatory Gene Therapy Using Oncolytic Viruses as Vehicles

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Angelica Loskog

2015-11-01

Full Text Available Immunostimulatory gene therapy has been developed during the past twenty years. The aim of immunostimulatory gene therapy is to tilt the suppressive tumor microenvironment to promote anti-tumor immunity. Hence, like a Trojan horse, the gene vehicle can carry warriors and weapons into enemy territory to combat the tumor from within. The most promising immune stimulators are those activating and sustaining Th1 responses, but even if potent effects were seen in preclinical models, many clinical trials failed to show objective responses in cancer patients. However, with new tools to control ongoing immunosuppression in cancer patients, immunostimulatory gene therapy is now emerging as an interesting option. In parallel, oncolytic viruses have been shown to be safe in patients. To prolong immune stimulation and to increase efficacy, these two fields are now merging and oncolytic viruses are armed with immunostimulatory transgenes. These novel agents are racing towards approval as established cancer immunotherapeutics.

A new rapid method for direct antimicrobial susceptibility testing of bacteria from positive blood cultures.

Science.gov (United States)

Barnini, Simona; Brucculeri, Veronica; Morici, Paola; Ghelardi, Emilia; Florio, Walter; Lupetti, Antonella

2016-08-12

Rapid identification and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections can lead to prompt appropriate antimicrobial therapy. To shorten species identification, in this study bacteria were recovered from monomicrobial blood cultures by serum separator tubes and spotted onto the target plate for direct MALDI-TOF MS identification. Proper antibiotics were selected for direct AST based on species identification. In order to obtain rapid AST results, bacteria were recovered from positive blood cultures by two different protocols: by serum separator tubes (further referred to as PR1), or after a short-term subculture in liquid medium (further referred to as PR2). The results were compared with those obtained by the method currently used in our laboratory consisting in identification by MALDI-TOF and AST by Vitek 2 or Sensititre on isolated colonies. The direct MALDI-TOF method concordantly identified with the current method 97.5 % of the Gram-negative bacteria and 96.1 % of the Gram-positive cocci contained in monomicrobial blood cultures. The direct AST by PR1 and PR2 for all isolate/antimicrobial agent combinations was concordant/correct with the current method for 87.8 and 90.5 % of Gram-negative bacteria and for 93.1 and 93.8 % of Gram-positive cocci, respectively. In particular, 100 % categorical agreement was found with levofloxacin for Enterobacteriaceae by both PR1 and PR2, and 99.0 and 100 % categorical agreement was observed with linezolid for Gram-positive cocci by PR1 and PR2, respectively. There was no significant difference in accuracy between PR1 and PR2 for Gram-negative bacteria and Gram-positive cocci. This newly described method seems promising for providing accurate AST results. Most importantly, these results would be available in a few hours from blood culture positivity, which would help clinicians to promptly confirm or streamline an effective antibiotic therapy in patients with bloodstream

Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

Science.gov (United States)

Sordillo, Peter P; Helson, Lawrence

2015-01-01

The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

International Nuclear Information System (INIS)

Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

2006-01-01

Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

Study of $(W/Z)H$ production and Higgs boson couplings using $H \\rightarrow WW^{\\ast}$ decays with the ATLAS detector

CERN Document Server

Aad, Georges; Abdallah, Jalal; Abdinov, Ovsat; Aben, Rosemarie; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Affolder, Tony; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; 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Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozic, Ivan; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Bristow, Kieran; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Brown, Jonathan; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bryngemark, Lene; Buanes, Trygve; 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Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerio, Benjamin; Cerny, Karel; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chang, Philip; Chapleau, Bertrand; Chapman, John Derek; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Childers, John Taylor; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Choi, Kyungeon; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christodoulou, Valentinos; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioara, Irina Antonela; Ciocio, Alessandra; Citron, Zvi Hirsh; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey Rogers; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Doglioni, Caterina; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dyndal, Mateusz; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Erdmann, Johannes; Ereditato, Antonio; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Francis, David; Franconi, Laura; Franklin, Melissa; Fraternali, Marco; Freeborn, David; French, Sky; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Geisler, Manuel Patrice; Gemme, Claudia; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gibbard, Bruce; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giromini, Paolo; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Guan, Liang; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Gupta, Shaun; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Hall, David; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Makoto; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Hejbal, Jiri; Helary, Louis; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hinman, Rachel Reisner; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohlfeld, Marc; Hohn, David; Holmes, Tova Ray; Homann, Michael; Hong, Tae Min; Hooft van Huysduynen, Loek; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Qipeng; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Ilchenko, Iurii; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivarsson, Jenny; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansky, Roland; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jejelava, Juansher; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Yi; Jiggins, Stephen; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kajomovitz, Enrique; Kalderon, Charles William; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karamaoun, Andrew; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharlamov, Alexey; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kivernyk, Oleh; Kladiva, Eduard; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, J örn Christian; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Shu; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Liblong, Aaron; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan; Long, Robin Eamonn; Looper, Kristina Anne; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maier, Thomas; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mantoani, Matteo; Mapelli, Livio; March, Luis; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marjanovic, Marija; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazza, Simone Michele; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Mortensen, Simon Stark; Morton, Alexander; Morvaj, Ljiljana; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Ralph Soeren Peter; Mueller, Thibaut; Muenstermann, Daniel; Mullen, Paul; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nomachi, Masaharu; Nomidis, Ioannis; Nooney, Tamsin; Norberg, Scarlet; Nordberg, Markus; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Palma, Alberto; Pan, Yibin; Panagiotopoulou, Evgenia; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Pauly, Thilo; Pearce, James; Pearson, Benjamin; Pedersen, Lars Egholm; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penwell, John; Perepelitsa, Dennis; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Pettersson, Nora Emilia; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Pickering, Mark Andrew; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinfold, James; Pingel, Almut; Pinto, Belmiro; Pires, Sylvestre; Pitt, Michael; Pizio, Caterina; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Pluth, Daniel; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Polesello, Giacomo; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Prell, Soeren; Price, Darren; Price, Lawrence; Primavera, Margherita; Prince, Sebastien; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopapadaki, Eftychia-sofia; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Ptacek, Elizabeth; Puddu, Daniele; Pueschel, Elisa; Puldon, David; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quarrie, David; Quayle, William; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Rajagopalan, Srinivasan; Rammensee, Michael; Rangel-Smith, Camila; Rauscher, Felix; Rave, Stefan; Ravenscroft, Thomas; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reisin, Hernan; Relich, Matthew; Rembser, Christoph; Ren, Huan; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Rud, Viacheslav; Rudolph, Christian; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Saddique, Asif; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saimpert, Matthias; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sannino, Mario; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sasaki, Osamu; Sasaki, Yuichi; Sato, Koji; Sauvage, Gilles; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Scarfone, Valerio; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R~Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Schiavi, Carlo; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitt, Stefan; Schneider, Basil; Schnellbach, Yan Jie; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schroeder, Christian; Schuh, Natascha; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schwegler, Philipp; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Sessa, Marco; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyedruhollah; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Shushkevich, Stanislav; Sicho, Petr; Sidiropoulou, Ourania; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silver, Yiftah; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Dorian; Simoniello, Rosa; Sinervo, Pekka; Sinev, Nikolai; Siragusa, Giovanni; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinner, Malcolm Bruce; Skottowe, Hugh Philip; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Matthew; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopczak, Andre; Sopko, Bruno; Sopko, Vit; Sorin, Veronica; Sosa, David; Sosebee, Mark; Sotiropoulou, Calliope Louisa; Soualah, Rachik; Soueid, Paul; Soukharev, Andrey; South, David; Spagnolo, Stefania; Spalla, Margherita; Spanò, Francesco; Spearman, William Robert; Spettel, Fabian; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; Spreitzer, Teresa; St Denis, Richard Dante; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Stavina, Pavel; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramaniam, Rajivalochan; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Shota; Suzuki, Yu; Svatos, Michal; Swedish, Stephen; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Taccini, Cecilia; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Shuji; Tannenwald, Benjamin Bordy; Tannoury, Nancy; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Ray; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tiouchichine, Elodie; Tipton, Paul; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; True, Patrick; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turra, Ruggero; Turvey, Andrew John; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Ueda, Ikuo; Ueno, Ryuichi; Ughetto, Michael; Ugland, Maren; Uhlenbrock, Mathias; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valderanis, Chrysostomos; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; Van Der Leeuw, Robin; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vannucci, Francois; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloso, Filipe; Velz, Thomas; Veneziano, Stefano; Ventura, Andrea; 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Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Xiaoxiao; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; Wharton, Andrew Mark; White, Andrew; White, Martin; White, Ryan; White, Sebastian; Whiteson, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, Alan; Wilson, John; Wingerter-Seez, Isabelle; Winklmeier, Frank; Winter, Benedict Tobias; Wittgen, Matthias; Wittkowski, Josephine; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wu, Mengqing; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xu, Da; Xu, Lailin; Yabsley, Bruce; Yacoob, Sahal; Yakabe, Ryota; Yamada, Miho; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yao, Liwen; Yao, Weiming; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yen, Andy L; Yildirim, Eda; Yorita, Kohei; Yoshida, Rikutaro; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, David Ren-Hwa; Yu, Jaehoon; Yu, Jiaming; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Yusuff, Imran; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanello, Lucia; Zanzi, Daniele; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Jinlong; Zhang, Lei; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Chen; Zhou, Lei; Zhou, Li; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zwalinski, Lukasz

2015-08-27

A search for Higgs boson production in association with a $W$ or $Z$ boson, in the $H \\rightarrow WW^{\\ast}$ decay channel, is performed with a data sample collected with the ATLAS detector at the LHC in proton-proton collisions at centre-of-mass energies $\\sqrt{s}=7$ TeV and 8 TeV, corresponding to integrated luminosities of 4.5 ${\\rm fb}^{-1}$ and 20.3 ${\\rm fb}^{-1}$, respectively. The $WH$ production mode is studied in two-lepton and three-lepton final states, while two-lepton and four-lepton final states are used to search for the $ZH$ production mode. The observed significance, for the combined $WH$ and $ZH$ production, is 2.5 standard deviations while a significance of 0.9 standard deviations is expected in the Standard Model Higgs boson hypothesis. The ratio of the combined $WH$ and $ZH$ signal yield to the Standard Model expectation, $\\mu_{VH}$, is found to be $\\mu_{VH} =3.0^{+1.3}_{-1.1}{\\, {(\\rm stat.)}}^{+1.0}_{-0.7}{\\,{(\\rm sys.)}}$ for the Higgs boson mass of 125.36 GeV. The $WH$ and $ZH$ produc...

Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication.

Science.gov (United States)

McBrien, Julia Bergild; Kumar, Nitasha A; Silvestri, Guido

2018-02-10

In this article, we summarize the role of CD8 + T cells during natural and antiretroviral therapy (ART)-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8 + T cell-based HIV cure strategies. Evidence suggests that CD8 + T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8 + T cells is responsible for control of viremia. However, it has been proposed that CD8 + T cells also use non-cytolytic mechanisms to control SIV infection. More recently, CD8 + T cells were shown to be required to fully suppress virus production in ART-treated SIV-infected macaques, suggesting that CD8 + T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8 + T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Applying Magneto-rheology to Reduce Blood Viscosity and Suppress Turbulence to Prevent Heart Attacks

Science.gov (United States)

Tao, R.

Heart attacks are the leading causes of death in USA. Research indicates one common thread, high blood viscosity, linking all cardiovascular diseases. Turbulence in blood circulation makes different regions of the vasculature vulnerable to development of atherosclerotic plaque. Turbulence is also responsible for systolic ejection murmurs and places heavier workload on heart, a possible trigger of heart attacks. Presently, neither medicine nor method is available to suppress turbulence. The only method to reduce the blood viscosity is to take medicine, such as aspirin. However, using medicine to reduce the blood viscosity does not help suppressing turbulence. In fact, the turbulence gets worse as the Reynolds number goes up with the viscosity reduction by the medicine. Here we report our new discovery: application of a strong magnetic field to blood along its flow direction, red blood cells are polarized in the magnetic field and aggregated into short chains along the flow direction. The blood viscosity becomes anisotropic: Along the flow direction the viscosity is significantly reduced, but in the directions perpendicular to the flow the viscosity is considerably increased. In this way, the blood flow becomes laminar, turbulence is suppressed, the blood circulation is greatly improved, and the risk for heart attacks is reduced. While these effects are not permanent, they last for about 24 hours after one magnetic therapy treatment.

Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation.

Science.gov (United States)

Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W

2014-09-24

Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P < 0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P = 0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4 cell count or CNS penetration-efficacy score. Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.

Regional Extent of Peripheral Suppression in Amblyopia.

Science.gov (United States)

Babu, Raiju J; Clavagnier, Simon; Bobier, William R; Thompson, Benjamin; Hess, Robert F

2017-04-01

Previously, we have mapped amblyopic eye suppression within the central 20° of the visual field and observed a gradient of suppression that is strongest in central vision and weakens with increasing eccentricity. In this study, using a large dichoptic display, we extend our novel suppression mapping approach further into the periphery (from 20°-60°) to assess whether suppression continues to decline with eccentricity or plateaus. Sixteen participants with amblyopia (10 with strabismus, 6 with anisometropia without strabismus; mean age: 37.9 ± 11 years) and six normal observers (mean age: 28.3 ± 5 years) took part. The visual stimulus (60° diameter), viewed from 57 cm, was composed of four concentric annuli (5° radius) with alternate contrast polarities starting from an eccentricity of 10°. Each annulus was divided into eight sectors subtending 45° of visual angle. Participants adjusted the contrast of a single sector presented to the fellow eye to match the perceived contrast of the remaining stimulus elements that were presented to the amblyopic eye. A matching contrast that was lower in the fellow eye than the amblyopic eye indicated suppression. Patients with strabismus exhibited significantly stronger interocular suppression than controls across all eccentricities (P = 0.01). Patients with anisometropia did not differ from controls (P = 0.58). Suppression varied significantly with eccentricity (P = 0.005) but this effect did not differ between patient groups (P = 0.217). In amblyopia, suppression is present beyond the central 10° in patients with strabismus. Suppression becomes weaker at greater eccentricities and this may enable peripheral fusion that could be used by binocular treatment methods.

High levels of adherence and viral suppression in a nationally representative sample of HIV-infected adults on antiretroviral therapy for 6, 12 and 18 months in Rwanda.

Directory of Open Access Journals (Sweden)

Batya Elul

Full Text Available BACKGROUND: Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART in Africa. METHODS: We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL measurements. Multivariable logistic regression examined predictors of non-perfect (40 copies/ml. RESULTS: Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months; younger age; reporting severe (vs. no or few side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL; alcohol use; and attending sites which initiated ART services in 2003-2004 and 2005 (vs. 2006-2007; sites with ≥600 (vs. <600 patients on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL. CONCLUSIONS: High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.

Postpartum Engagement in HIV Care: An Important Predictor of Long-term Retention in Care and Viral Suppression.

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Adams, Joëlla W; Brady, Kathleen A; Michael, Yvonne L; Yehia, Baligh R; Momplaisir, Florence M

2015-12-15

Human immunodeficiency virus (HIV)-infected women are at risk of virologic failure postpartum. We evaluated factors influencing retention in care and viral suppression in postpartum HIV-infected women. We conducted a retrospective cohort analysis (2005-2011) of 695 deliveries involving 561 HIV-infected women in Philadelphia. Multivariable logistic regression evaluated factors, including maternal age, race/ethnicity, substance use, antiretroviral therapy during pregnancy, timing of HIV diagnosis, previous pregnancy with HIV, adequacy of prenatal care, and postpartum HIV care engagement (≥ 1 CD4 count or viral load [VL] test within 90 days of delivery), associated with retention in care (≥ 1 CD4 count or VL test in each 6-month interval of the period with ≥ 60 days between tests) and viral suppression (VL ≤ 200 copies/mL at the last measure in the period) at 1 and 2 years postpartum. Overall, 38% of women engaged in HIV care within 90 days postpartum; with 39% and 31% retained in care and virally suppressed, respectively, at 1 year postpartum, and 25% and 34% retained in care and virally suppressed, respectively, at 2 years postpartum. In multivariable analyses, women who engaged in HIV care within 90 days of delivery were more likely to be retained (adjusted odds ratio [AOR], 11.38; 95% confidence interval [CI], 7.74-16.68) and suppressed (AOR, 2.60 [95% CI, 1.82-3.73]) at 1 year postpartum. This association persisted in the second year postpartum for both retention (AOR, 6.19 [95% CI, 4.04-9.50]) and suppression (AOR, 1.40 [95% CI, 1.01-1.95]). The prevalence of postpartum HIV-infected women retained in care and maintaining viral suppression is low. Interventions seeking to engage women in care shortly after delivery have the potential to improve clinical outcomes. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review

International Nuclear Information System (INIS)

Sasse, André D; Sasse, Elisa; Carvalho, Albertina M; Macedo, Ligia T

2012-01-01

Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity. Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals. Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long-term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy. Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases

Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer

International Nuclear Information System (INIS)

Frusciante, V.; Dicembrino, F.; Carnevale, V.; Scillitani, A.; Zingrillo, M.; Ghiggi, M.R.; Giannatempo, G.M.; Minisola, S.

1998-01-01

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T 4 ) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T 4 suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T 4 . All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward's triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T 4 or results of thyroid function tests. Our data show that carefully monitored l-T 4 therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur. (orig.)

Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer

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Frusciante, V.; Dicembrino, F. [Department of Nuclear Medicine, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Carnevale, V. [Division of Internal Medicine, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Scillitani, A.; Zingrillo, M.; Ghiggi, M.R. [Division of Endocrinology, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Giannatempo, G.M. [Department of Radiology, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Minisola, S. [Istituto di II Clinica Medica, Universita degli Studi di Roma ``La Sapienza``, Rome (Italy)

1998-02-01

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T{sub 4}) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T{sub 4} suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T{sub 4}. All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward`s triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T{sub 4} or results of thyroid function tests. Our data show that carefully monitored l-T{sub 4} therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur. (orig.) With 1 fig., 2 tabs., 36 refs.

CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

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Tsai, Cheng Ying [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Douglas, David R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Li, Rui [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Tennant, Christopher D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); di Mitri, Simone [Elettra–Sincrotrone Trieste, 34149 Basovizza, Trieste, Italy

2016-05-01

The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

Therapy of endemic goiter and hypothyroidism

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Luft, D.

1983-09-12

Successful treatment of endemic goitre depends on the correct diagnosis and the comprehension of the pathophysiologic changes as well. Several criteria, e.g. anamnestic data, general clinical condition, local symptoms and signs, certainty of diagnosis, contraindications, rates of success, and side effects, determine the particular form of therapy (suppression with thyroid hormones, surgical resection, radio-iodine). The decision criteria are discussed. Prophylaxis of recurrent goitre with either thyroid hormones or iodine salts is necessary after successful treatment. Some endemic goitres behave like either hyper- or hypothyroidism. Treatment with thyroid hormones of patients with latent hyperthyroidism is senseless and dangerous, whereas other methods of treatment may be applied. An unequivocal indication for treatment exists in patients with latent hypothyroidism accompanied by goitre, but not in all patients without goitre. Hormonal replacement therapy of manifest hypothydroidism is simple, but long term success is not achieved in all patients.

Therapy of endemic goiter and hypothyroidism

International Nuclear Information System (INIS)

Luft, D.

1983-01-01

Successful treatment of endemic goitre depends on the correct diagnosis and the comprehension of the pathophysiologic changes as well. Several criteria, e.g. anamnestic data, general clinical condition, local symptoms and signs, certainty of diagnosis, contraindications, rates of success, and side effects, determine the particular form of therapy (suppression with thyroid hormones, surgical resection, radio-iodine). The decision criteria are discussed. Prophylaxis of recurrent goitre with either thyroid hormones or iodine salts is necessary after successful treatment. Some endemic goitres behave like either hyper- or hypothyroidism. Treatment with thyroid hormones of patients with latent hyperthyroidism is senseless and dangerous, whereas other methods of treatment may be applied. An unequivocal indication for treatment exists in patients with laent hypothyroidism accompanied by goitre, but not in all patients without goitre. Hormonal replacement therapy of manifest hypothydroidism is simple, but long term success is not achieved in all patients. (orig.) [de

Maternal deaths following nevirapine-based antiretroviral therapy

Directory of Open Access Journals (Sweden)

E Bera

2012-10-01

Full Text Available We report 2 cases illustrating that it is too simplistic to link nevirapine (NVP toxicity exclusively to individuals with immune preservation. Not enough is known about the mechanism of hepatotoxicity or cutaneous eruption to predict these events. This type of hypersensitivity reaction occurs rarely among HIV-exposed infants taking NVP prophylaxis or antiretroviral therapy (ART-experienced adults with complete plasma viral load suppression. Conversely, HIV-uninfected adults and ART-naive pregnant women appear to be disproportionately affected by the adverse effects of NVP.

GENE EXPRESSION DYNAMICS IN PATIENTS WITH SEVERE THERAPY-RESISTANT ASTHMA DURING TREATMENT PERIOD

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Ye. S. Kulikov

2014-01-01

Full Text Available Introduction: The leading mechanisms and causes of severe therapy resistant asthma are poorly understood. The aim of this study was to define global patterns of gene expression in adults with severe therapy-resistant asthma in dynamic during treatment period.Methods: Performed 24-week prospective interventional study in parallel groups. Severe asthma patients was aposterior divided at therapy sensitive and resistant patients according to ATS criteria. Global transcriptome profile was characterized using the Affymetrix HuGene ST1.0 chip. Cluster analysis was performed.Results and conclusion: According to our data several mechanisms of therapy resistance may be considered: increased levels of nitric oxide and beta2-agonists nitration, dysregulation of endogenous steroids secretion and involvement in the pathogenesis of Staphylococcus aureus. Absence of suppression of gene expression KEGG-pathway “asthma" may reflect the low efficiency or long period of anti-inflammatory therapy effect realization.

The role of chloroplasts in plant pathology.

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Sowden, Robert G; Watson, Samuel J; Jarvis, Paul

2018-04-13

Plants have evolved complex tolerance systems to survive abiotic and biotic stresses. Central to these programmes is a sophisticated conversation of signals between the chloroplast and the nucleus. In this review, we examine the antagonism between abiotic stress tolerance (AST) and immunity: we propose that to generate immunogenic signals, plants must disable AST systems, in particular those that manage reactive oxygen species (ROS), while the pathogen seeks to reactivate or enhance those systems to achieve virulence. By boosting host systems of AST, pathogens trick the plant into suppressing chloroplast immunogenic signals and steer the host into making an inappropriate immune response. Pathogens disrupt chloroplast function, both transcriptionally-by secreting effectors that alter host gene expression by interacting with defence-related kinase cascades, with transcription factors, or with promoters themselves-and post-transcriptionally, by delivering effectors that enter the chloroplast or alter the localization of host proteins to change chloroplast activities. These mechanisms reconfigure the chloroplast proteome and chloroplast-originating immunogenic signals in order to promote infection. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Suppression of gastric cancer dissemination by ephrin-B1-derived peptide.

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Tanaka, Masamitsu; Kamata, Reiko; Yanagihara, Kazuyoshi; Sakai, Ryuichi

2010-01-01

Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bidirectional signaling through cell-cell contacts. High expression of B-type ephrin is associated with high invasion potential of tumors, and we previously observed that signaling through the C-terminus of ephrin-B1 mediates the migration and invasion of cells, and is involved in the promotion of carcinomatous peritonitis in vivo. Here we show that the intracellular introduction of a synthetic peptide derived from ephrin-B1 C-terminus blocks ephrin-B1 mediated signaling in scirrhous gastric cancer cells. Treatment of cancer cells with a fusion peptide consisting of HIV-TAT and amino acids 331-346 of ephrin-B1 (PTD-EFNB1-C) suppressed the activation of RhoA, mediated by the association of ephrin-B1 with an adaptor protein Dishevelled, and also inhibited extracellular secretion of metalloproteinase. Moreover, injection of PTD-EFNB1-C peptide into the peritoneal cavity of nude mice suppressed carcinomatous peritonitis of intraperitoneally transplanted scirrhous gastric cancer cells. These results indicate the possible application of ephrin-B1 C-terminal peptide to develop novel protein therapy for scirrhous gastric carcinoma, especially in the stage of tumor progression, including peritoneal dissemination.

Optimal Control of Drug Therapy in a Hepatitis B Model

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Jonathan E. Forde

2016-08-01

Full Text Available Combination antiviral drug therapy improves the survival rates of patients chronically infected with hepatitis B virus by controlling viral replication and enhancing immune responses. Some of these drugs have side effects that make them unsuitable for long-term administration. To address the trade-off between the positive and negative effects of the combination therapy, we investigated an optimal control problem for a delay differential equation model of immune responses to hepatitis virus B infection. Our optimal control problem investigates the interplay between virological and immunomodulatory effects of therapy, the control of viremia and the administration of the minimal dosage over a short period of time. Our numerical results show that the high drug levels that induce immune modulation rather than suppression of virological factors are essential for the clearance of hepatitis B virus.

Further research needed to support a policy of antiretroviral therapy as an HIV prevention initiative

DEFF Research Database (Denmark)

Rodger, Alison J; Bruun, Tina; Vernazza, Pietro

2013-01-01

The results from the HPTN 052 trial have increased the focus on use of antiretroviral therapy (ART) for prevention of HIV transmission; however, condom use also effectively prevents HIV transmission. Studies in heterosexual serodiscordant couples with viral suppression have so far only reported f...

Waldenström makroglobulinemili hastada rituksimab tedavisi sonrası gelişen gizli hepatit B reaktivasyonu

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Vedat Aslan

2012-12-01

Full Text Available The anti-CD20 monoclonal antibody rituximab has beenused extensively in the treatment of B-cell lymphoma.Several studies reported hepatitis B virus (HBV reactivationafter rituximab. The majority of these cases havebeen described in chronic carriers of HBV, whereas reactivationin occult hepatitis B virus (OHBV carriers mayoccur.The presented case with the diagnosis of Waldenström’smacroglobulinemia was HBsAg negative and anti HBcIgGpositive before chemotherapy. The patient was started onCVP (cyclophosphamide, vincristine, prednisolone chemotherapy.However, no clinical or laboratory responsewas obtained and the patient was considered unresponsiveto three cycles of CVP therapy. Therefore R-CHOP(rituximab, cyclophosphamide, adriamycin, vincristineand prednisolone was planned as the second therapy.Laboratory work-up after the first cycle of R-CHOP therapyrevealed an aspartate aminotransferase (AST levelof 267 U/L and alanine aminotransferase (ALT level of318 U/L. HBsAg and anti HBcIgG were positive and HBVDNA was 56400 IU/ml. Lamivudin 100 mg/day was started.Four weeks after the initiation of lamivudin therapy,ALT and AST levels returned to normal. Currently, the patienthas received the fourth cycle of R-CHOP therapy.ALT and AST levels continue to be in normal range. Thiscondition was considered to be the reactivation of OHBVfollowing rituximab.The aim of this case presentation is to call attention toHBV reactivation possibility in cases taking immunosupressivemedications like Rituximab. J Clin Exp Invest2012; 3(4: 541-544Key words: Waldenström’s macroglobulinemia, rituximab,occult HBV infection

Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

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Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

2006-01-01

Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.

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Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L; Liao, Gongxian; Hoffman, Brad E; Leong, Kam W; Terhorst, Cox; Daniell, Henry; Herzog, Roland W

2015-04-09

Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)-dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80(+) cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103(+) and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4(+) regulatory T cells (CD4(+)CD25(-)LAP(+) cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4(+)CD25(+) regulatory T cells systemically suppressed anti-FIX responses. © 2015 by The American Society of Hematology.

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3). Combination effect on the metastatic tumors

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Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-03-01

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF/sub 1/ mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

CD4+ Count-Guided Interruption of Antiretroviral Treatment. The Strategies for Mangement of Antiretroviral Therapy (SMART) Study Group

DEFF Research Database (Denmark)

El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD

2006-01-01

had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less......BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who...... the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society....

Benchmark enclosure fire suppression experiments - phase 1 test report.

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Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

2007-06-01

A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

Bilateral optic neuritis in a child diagnosed with Gd-enhanced MR imaging using fat-suppression technique

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Okamoto, K.; Ogawa, R.; Furusawa, T.; Sakai, K. [Dept. of Radiology, Niigata Univ. School of Medicine, Niigata (Japan); Ito, J.; Tokiguchi, S. [Dept. of Radiology, Niigata University School of Dentistry (Japan); Takagi, M. [Dept. of Ophthalmology, Niigata Univ. School of Medicine (Japan)

1999-05-01

A 4-year-old boy developed bilateral optic neuritis. Although precise neuro-ophthalmological evaluation was difficult, the diagnosis was made with gadolinium-enhanced MR imaging using fat-suppression technique in the initial stage of the disease. Enhancement and enlargement of the intraorbital and intracanalicular optic nerve were demonstrated bilaterally as well as protrusion of the optic nerve head. The disease responded dramatically to intravenous steroid therapy. The etiologies in children usually differ from those in adolescent and adult patients. (orig.) With 1 fig., 13 refs.

Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

Science.gov (United States)

Lapsia, Sameer; Koganti, Siva; Spadaro, Salvatore; Rajapakse, Ramona; Chawla, Anupama; Bhaduri-McIntosh, Sumita

2016-02-01

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. © 2015 Wiley Periodicals, Inc.

Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.

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Janardhanan, Manju; Amberkar V, Mohan Babu; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N

2014-09-01

The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/μL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.

Photodynamic therapy: A new vista in management of periodontal diseases

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Yogesh Doshi

2010-01-01

Full Text Available Aim: The purpose of this review was to evaluate the effectiveness of photodynamic therapy (PDT for periodontitis. This review also elucidates application of photodynamic therapy for noninvasive management of periodontitis without leading to bacterial resistance. Background: Periodontal diseases are one of the major causes of tooth loss in adults and are considered primarily an anaerobic bacterial infections caused by the so-called red complex species. Bacteria present in a biofilm community, enzymes, endotoxins, and other cytotoxic factors lead to tissue destruction and initiate chronic inflammation. Since many years pioneers have been working to provide logical and cost-effective therapy for management of periodontitis. Periodontal researchers have found that PDT is advantageous to suppress anaerobic bacteria. Clinical Significance: Applications of PDT in dentistry are growing rapidly. PDT application has an adjunctive benefit besides mechanical treatment at sites with difficult access. Necessity for flap surgery may be reduced, patient comfort may increase, and treatment time may decrease. The application of photosensitizing dyes and their excitation by visible light enables effective killing of periodonto-pathogens. The introduction of laser along with photosensitizers has brought a revolutionary change. Conclusion: The application of photodynamic therapy in management of periodontal diseases is very valuable. The therapy should be combined with nonsurgical periodontal therapy. Proper clinical application of photodynamic therapy can and will help patients who are systemically compromised and cannot undergo surgical therapy.

Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

Directory of Open Access Journals (Sweden)

Sandra A Springer

Full Text Available HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD.From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

Androgens as therapy for androgen receptor-positive castration-resistant prostate cancer

Directory of Open Access Journals (Sweden)

Lin Hui-Ping

2011-08-01

Full Text Available Abstract Prostate cancer is the most frequently diagnosed non-cutaneous tumor of men in Western countries. While surgery is often successful for organ-confined prostate cancer, androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. Shortening the period of androgen ablation therapy may benefit prostate cancer patients. Intermittent Androgen Deprivation therapy improves quality of life, reduces toxicity and medical costs, and delays disease progression in some patients. Cell culture and xenograft studies using androgen receptor (AR-positive castration-resistant human prostate cancers cells (LNCaP, ARCaP, and PC-3 cells over-expressing AR suggest that androgens may suppress the growth of AR-rich prostate cancer cells. Androgens cause growth inhibition and G1 cell cycle arrest in these cells by regulating c-Myc, Skp2, and p27Kip via AR. Higher dosages of testosterone cause greater growth inhibition of relapsed tumors. Manipulating androgen/AR signaling may therefore be a potential therapy for AR-positive advanced prostate cancer.

Usefulness of combined fat- and fluid-suppressed SPIR-FLAIR images in optic neurits : Comparison with fat-suppressed SPIR or STIR images

International Nuclear Information System (INIS)

Kim, Hye Yeon; Son, Seok Hyun; Eun, Choong Ki; Han, Sang Suk

2001-01-01

To compare the usefulness of combined fat- and fluid-suppressed selective partial inversion recovery-fluid attenuated inversion recovery(SPIR-FLAIR) images in the detection of high signal intensity of the optic nerve in optic neuritis with that of fat-suppressed selective partial inversion recovery(SPIR) or short inversion time inversion recovery(STIR) images. Two radiologists independently analyzed randomly mixed MR images of 16 lesions in 14 patients (M:F=7:7; mean age, 40 years) in whom optic neuritis had been clinically diagnosed. All subjects underwent both SPIR-FLAIR and fat-suppressed SPIR or STIR imaging, in a blind fashion. In order to evaluate the optic nerve, coronal images perpendicular to its long axis were obtained. The detection rate of high signal intensity of the optic nerve, the radiologists preferred imaging sequences, and intersubject consistency of detection were evaluated. 'High signal intensity' was defined as the subjective visual evaluation of increased signal intensity compared with that of the contralateral optic nerve or that of white matter. The mean detection rate of high signal intensity of the optic nerve was 90% for combined fat- and fluid-suppressed SPIR-FLAIR images, and 59% for fat-suppressed SPIR or STIR images. In all cases in which the signal intensity observed on SPIR-FLAIR images was normal, that on fat-suppressed SPIR or STIR images was also normal. The radiologists preferred the contrast properties of SPIR-FLAIR to those of fat-suppressed SPIR or STIR images. In the diagnosis of optic neuritis using MRI, combined fat- and fluid-suppressed SPIR-FLAIR images were more useful for the detection of high signal intensity of the optic nerve than fat-suppressed SPIR or STIR images. For the evaluation of optic neuritis, combined fat- and fluid-suppressed SPIR-FLAIR imaging is superior to fat-suppressed SPIR or STIR imaging

Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

OpenAIRE

El-Badri, Nagwa; Ghoneim, Mohamed A.

2013-01-01

Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy...

Exploring Genetic Suppression Interactions on a Global Scale

OpenAIRE

van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C.; Yamaguchi, Takafumi N.; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire

2016-01-01

Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insig...

Glutamine supplementation suppresses herpes simplex virus reactivation.

Science.gov (United States)

Wang, Kening; Hoshino, Yo; Dowdell, Kennichi; Bosch-Marce, Marta; Myers, Timothy G; Sarmiento, Mayra; Pesnicak, Lesley; Krause, Philip R; Cohen, Jeffrey I

2017-06-30

Chronic viral infections are difficult to treat, and new approaches are needed, particularly those aimed at reducing reactivation by enhancing immune responses. Herpes simplex virus (HSV) establishes latency and reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and proliferation of activated T cells requires increased metabolism of glutamine. Here, we found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1-infected mice and HSV-2-infected guinea pigs. Transcriptome analysis of trigeminal ganglia from latently HSV-1-infected, glutamine-treated WT mice showed upregulation of several IFN-γ-inducible genes. In contrast to WT mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in latently HSV-1-infected IFN-γ-KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-γ-producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

Chondromalacia patellae: fat-suppressed MR imaging.

Science.gov (United States)

Rose, P M; Demlow, T A; Szumowski, J; Quinn, S F

1994-11-01

To evaluate the accuracy of fat-suppressed magnetic resonance (MR) imaging in diagnosing chondromalacia patellae. Seventy-one patients underwent fat-suppressed MR imaging and arthroscopy of the patellofemoral compartment. Findings were classified as early or advanced chondromalacia or as normal and were correlated with arthroscopic findings. Early and advanced stages of chondromalacia patellae were reliably detected, with positive predictive values of 85% and 92%, respectively. Specificity in early stages was 94% and in late stages was 98%. However, the overall accuracies did not differ substantially from those reported in studies that did not use fat-suppressed imaging. Axial, fat-suppressed MR imaging accurately depicts changes caused by chondromalacia patellae. Early stages can be seen as intrasubstance changes of increased signal intensity. Results of this study suggest a high degree of specificity in excluding both early and advanced changes.

Acid suppressants for managing gastro-oesophageal reflux and gastro-oesophageal reflux disease in infants: a national survey.

Science.gov (United States)

Bell, Jane C; Schneuer, Francisco J; Harrison, Christopher; Trevena, Lyndal; Hiscock, Harriet; Elshaug, Adam G; Nassar, Natasha

2018-02-22

To evaluate the diagnosis and management of reflux and gastro-oesophageal reflux disease (GORD) in infants aged reflux and GORD and their management including prescribing of acid-suppressant medicines (proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs)) and counselling, advice or education. Of all infants' visits, 512 (2.7%) included a diagnosis of reflux (n=413, 2.2%) or GORD (n=99, 0.5%). From 2006 to 2016, diagnostic rates decreased for reflux and increased for GORD. Prescribing of acid suppressants occurred in 43.6% visits for reflux and 48.5% visits for GORD, similar to rates of counselling, advice or education (reflux: 38.5%, GORD: 43.4% of visits). Prescribing of PPIs increased (statistically significant only for visits for reflux), while prescribing of H2RAs decreased. Overprescribing of acid suppressants to infants may be occurring. In infants, acid-suppressant medicines are no better than placebo and may have significant negative side effects; however, guidelines are inconsistent. Clear, concise and consistent guidance is needed. GPs and parents need to understand what is normal and limitations of medical therapy. We need a greater understanding of the influences on GP prescribing practices, of parents' knowledge and attitudes and of the pressures on parents of infants with these conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Suppressed visual looming stimuli are not integrated with auditory looming signals: Evidence from continuous flash suppression.

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Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond

2015-01-01

Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.

Thought Suppression Research Methods: Paradigms, Theories, Methodological Concerns

Directory of Open Access Journals (Sweden)

Niczyporuk Aneta

2016-12-01

Full Text Available It is hard to provide an unequivocal answer to the question of whether or not thought suppression is effective. Two thought suppression paradigms - the “white bear” paradigm and the think/no-think paradigm - give mixed results. Generally, “white bear” experiments indicate that thought suppression is counterproductive, while experiments in the think/no-think paradigm suggest that it is possible to effectively suppress a thought. There are also alternative methods used to study thought suppression, for instance the directed forgetting paradigm or the Stroop task. In the article, I describe the research methods used to explore thought suppression efficacy. I focus on the “white bear” and the think/no-think paradigms and discuss theories proposed to explain the results obtained. I also consider the internal and external validity of the methods used.

Accentuation-suppression and scaling

DEFF Research Database (Denmark)

Sørensen, Thomas Alrik; Bundesen, Claus

2012-01-01

The limitations of the visual short-term memory (VSTM) system have become an increasingly popular field of study. One line of inquiry has focused on the way attention selects objects for encoding into VSTM. Using the framework of the Theory of Visual Attention (TVA; Bundesen, 1990 Psychological...... a scaling mechanism modulating the decision bias of the observer and also through an accentuation-suppression mechanism that modulates the degree of subjective relevance of objects, contracting attention around fewer, highly relevant objects while suppressing less relevant objects. These mechanisms may...

Comprehensive Effects of Suppression of MicroRNA-383 in Human Bone-Marrow-Derived Mesenchymal Stem Cells on Treating Spinal Cord Injury

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Guo-Jun Wei

2018-05-01

Full Text Available Background/Aims: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs promotes neural cell regeneration after spinal cord injury (SCI. Recently, we showed that suppression of microRNA-383 (miR-383 in MSCs increased the protein levels of glial cell line derived neurotrophic factor (GDNF, resulting in improved therapeutic effects on SCI. However, the overall effects of miR-383 suppression in MSCs on SCI therapy were not determined yet. Here, we addressed this question. Methods: We used bioinformatics tools to predict all miR-383-targeting genes, confirmed the functional bindings in a dual luciferase reporter assay. The effects of alteration of candidate genes in MSCs on cell proliferation were analyzed by MTT assay and by Western blotting for PCNA. The effects on angiogenesis were assessed by HUVEC assay. The effects on SCI in vivo were analyzed by transplantation of the modified MSCs into nude rats that underwent SCI. Results: Suppression of miR-383 in MSCs not only upregulated GDNF protein, but also increased vascular endothelial growth factor A (VEGF-A and cyclin-dependent kinase 19 (CDK19, two other miR-383 targets. MiR-383-suppression-induced increases in CDK19 resulted in a slight but significant increase in MSC proliferation, while miR-383-suppression-induced increases in VEGF-A resulted in a slight but significant increase in MSC-mediated angiogenesis. Conclusions: Upregulation of CDK19 and VEGF-A by miR-383 suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats.

Treatment results of nasopharyngeal carcinoma with chemotherapy (cisplatin and 5-fluorouracil) and radiation therapy

International Nuclear Information System (INIS)

Fuwa, Nobukazu; Kato, Eriko; Ito, Yosiyuki; Kikuti, Yuzo

1995-01-01

Sixteen patients with nasopharyngeal cancer were treated with a combination chemotherapy consisting of cisplatin and 5-fluorouracil and radiation therapy. Systemic chemotherapy with cisplatin (50 mg/m 2 , 2 days) and 5-fluorouracil (700 mg/m 2 , 5 days) was given successively with radiation therapy. The complications of chemotherapy were generally acceptable except one patient who was shocked by cisplatin. The survival rate was significantly improved compared with historical control cases. The main reason for this effectiveness was the improvement of localized control. The suppression of distant metastasis is the subject of future research. (author)

Idiopathic scoliosis, growth zones, magnetic therapy.

Science.gov (United States)

Arsenev, A; Dudin, M; Lednev, V; Belova, N; Mikhailov, V; Sokolov, G

2012-01-01

The study has been performed to investigate the influence of pulsed magnetic field on the bone growth plates to get new grounds of magneto therapy in AIS treatment. Were used methods of "strong" and "weak" pulsed magnetic fields influence. Application of pulsed magnetic field causes an authentic inhibition of chondrocytes' active proliferation processes, decreases the index of labeled nuclei, indicating the suppression of DNA synthesis, takes place an increase in the unit weight of the more "mature" differentiated chondrocytes. The final result of these effects is the accelerated synostosis of bones' growth plates. Regardless of the reasons that cause growth infringements, the operating organ in the chain is the body's growth plate. Therefore, the appliance of magnetic fields in AIS treatment can be considered as a perspective one concerning growth plates' functional activity local management. To our point of view, the potential of magneto therapy methods in child's orthopedic treatment is significantly higher compared with modern practice.

Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival and

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Dmytro Starenki

2015-12-01

Full Text Available BackgroundMedullary thyroid carcinoma (MTC is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077, a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria.MethodsThe effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53, and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts.ResultsMKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts.ConclusionMKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC.

Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto.

Science.gov (United States)

Pan, Hung-Chuan; Yang, Dar-Yu; Ho, Shu-Peng; Sheu, Meei-Ling; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou

2009-08-23

Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.

Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto

Directory of Open Access Journals (Sweden)

Pan Hung-Chuan

2009-08-01

Full Text Available Abstract Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days; Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.

Molecular biology-based diagnosis and therapy for pancreatic cancer

International Nuclear Information System (INIS)

Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

2011-01-01

Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

Charmonium formation and suppression in nuclear matter

International Nuclear Information System (INIS)

Xu Jiajun; Wang Jia; Zhuang Chao; Zhuang Pengfei

2005-01-01

The coupling Schroedinger equations describing the evolution of cc-bar states in nuclear matter are analytically and systematically solved via perturbation method, and the correlation between charmonium formation and nuclear absorption is investigated. After calculating J/Ψ and Ψ' suppression in nucleon-nucleus collisions and comparing with experiment data, it is found that the formation time effect plays an important rule in charmonium suppression, especially in Ψ' suppression. (authors)

miR-216b suppresses breast cancer growth and metastasis by targeting SDCBP

International Nuclear Information System (INIS)

Jana, Samir; Sengupta, Suman; Biswas, Subir; Chatterjee, Annesha; Roy, Himansu; Bhattacharyya, Arindam

2017-01-01

Breast cancer is the most deadly cancer among women and the second leading cause of cancer death worldwide. Treatment effectiveness is complicated with tumor invasiveness/drug resistance. To tailor treatments more effectively to individual patients, it is important to define tumor growth and metastasis at molecular levels. SDCBP is highly overexpressed and associated with a strikingly poor prognosis in breast cancer. However the post transcriptional regulation of SDCBP overexpression remains to be an unexplored area. Our study reveals that miR-216b directly regulates SDCBP expression by binding to its 3′UTR region. miR-216b is a tumor suppressive miRNA and it is underexpressed during metastatic breast cancer. Consequently, overexpression of miR-216b resulted in decreased proliferation, migration and invasion in BC cell lines by modulating the expression of SDCBP. Inhibition of miR-216b divergent the tumor suppressive role by inducing the growth proliferation, migration and invasion in vitro. There is therefore a negative correlation between the expression of miR-216b and its target gene SDCBP in the BC tissue samples as well as cell lines. Simultaneous expression of miR-216b and SDCBP rescued the growth, migration and invasion effect suggesting that tumor suppressive action of miR-216b may be directly mediated by SDCBP. In summary, the study identifies miR-216b as a regulator of SDCBP expression in breast cancer which can potentially be targeted for developing newer therapies for the effective treatment of this killer disease.

One-tone suppression in the frog auditory nerve

DEFF Research Database (Denmark)

Christensen-Dalsgaard, J; Jørgensen, M B

1996-01-01

Sixty-seven fibers of a sample of 401 in the auditory nerve of grassfrogs (Rana temporaria) showed one-tone suppression, i.e., their spontaneous activity was suppressed by tones. All fibers were afferents from the amphibian papilla with best frequencies between 100 and 400 Hz. Best suppression...

Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders.

Science.gov (United States)

Conelea, Christine A; Wellen, Brianna; Woods, Douglas W; Greene, Deanna J; Black, Kevin J; Specht, Matthew; Himle, Michael B; Lee, Han-Joo; Capriotti, Matthew

2018-01-01

Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression.

Combustion suppressing device for leaked sodium

International Nuclear Information System (INIS)

Ooto, Akihiro.

1985-01-01

Purpose: To suppress the atmospheric temperature to secure the building safety and shorten the recovery time after the leakage in a chamber for containing sodium leaked from coolant circuit equipments or pipeways of LMFBR type rector by suppressing the combustion of sodium contained in the chamber. Constitution: To the inner wall of a chamber for containing sodium handling equipments, are vertically disposed a panel having a coolant supply port at the upper portion and a coolant discharge port at the lower portion thereof and defined with a coolant flowing channel and a panel for sucking the coolant discharged from the abovementioned panel and exhausting the same externally. Further, a corrugated combustion suppressing plate having apertures for draining the condensated leaked sodium is disposed near the sodium handling equipments. If ruptures are resulted to the sodium handling equipments or pipeway, leaked sodium is passed through the drain apertures in the suppressing plate and stored at the bottom of the containing chamber. (Horiuchi, T.)

131I therapy of thyroid cancer patients

International Nuclear Information System (INIS)

Reiners, C.; Farahati, J.

1999-01-01

Thyroid cancer is a rare malignancy with wide inter ethnic and geographic variations. In Germany thyroid carcinoma is the 13. most frequent malignancy (2.7 new cases yearly per 100,000 inhabitants). The overall temporal incidence is increasing slightly in recent years. The most common types of cancer are papillary (60-80%) and follicular cancers (10-20%). The relevant prognostic indicators are tumor stage and distant metastases. The mean survival rates in papillary thyroid cancer usually exceed 90%, whereas in follicular thyroid cancer they amount to approximately 80%. The standard treatment procedure in differentiated papillary and follicular thyroid cancer consists of total thyroidectomy followed by adjuvant ablative therapy with radioiodine. Only in papillary thyroid cancer stage pT 1 N 0 M 0 lobectomy alone is considered to be appropriate. In patients with locally invasive differentiated thyroid cancers stage pT 4 adjuvant percutaneous radiation therapy is a treatment option. Radioiodine therapy has to be performed under the stimulative influence of TSH. Usually TSH suppressive medication with Levothyroxine has to be withdrawn approximately 4 weeks prior to radioiodine therapy. In the future, exogenous stimulation by recombinant TSH may be used instead of thyroid hormone withdrawal. It has been proved by different studies that ablative radioiodine therapy reduces the frequency of recurrences and tumor spread in patients with thyroid cancer significantly. In patients with distant metastases, up to 50% of complete responses may be achieved with radioiodine treatment

Treatment of vitiligo vulgaris with the combination therapy of topical steroid and vitamin D3 compound

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Yoko Konishi

2012-06-01

Full Text Available We reported here two cases of vitiligo vulgaris successfully treated with the combination therapy of topical steroid and vitamin D3 compound and currently maintained by vitamin D3 analog without any adverse effects: skin atrophy, striae or telangiectasia on the exposed areas. The best-known mechanism of topical vitamin D3 analog is the enhancement of keratinocytes differentiation and anti-proliferative effects. Vitamin D3 analog is also reported to suppress T-cell mediated immunity, T-cell skin recruitment, and skin infiltration via down-regulating cutaneous lymphocyte antigen expression. Furthermore, vitamin D3 compounds are known to influence melanocyte maturation and differentiation and also to up-regulate melanogenesis. Autoreactive lymphocytes against melanocytes are one of the causes. Topical vitamin D3 analog may control vitiligo itself, however stronger immunosuppressive effects of topical corticosteroid may contribute to rapid re-pigmentation suppressing auto-reactive lymphocytes. The topical combination therapy is a simple, effective and safe option for vitiligo vulgaris in sun-exposed areas.

Effectiveness of L-thyroxine treatment on TSH suppression during pregnancy in patients with a history of thyroid carcinoma after total thyroidectomy and radioiodine ablation

International Nuclear Information System (INIS)

Krhin, Blaz; Besic, Nikola

2012-01-01

There are scarce data about the optimal increase of L-thyroxine dose during pregnancy in patients with a history of thyroid carcinoma. The first aim of the study was to find out if routine therapeutic measures enable adequate TSH suppression in pregnancy. The other aim was to find out the optimal dose of L-thyroxine for TSH suppression in pregnant women. In this retrospective observational study, we analysed 36 pregnancies of 32 women with a history of thyroid carcinoma. Before pregnancy, all of them underwent total thyroidectomy and radioiodine ablation of thyroid remnant, and they were on suppressive doses of L-thyroxine. Thyroid function tests were obtained before, during and after pregnancy. Mean L-thyroxine dose before pregnancy, in the first, second and, third trimester and after delivery was 149, 147, 155, 165 and 158 micrograms daily, respectively. TSH concentration remained suppressed in 9 pregnancies, it was within normal range in 22 and elevated in 5 pregnancies. The mean dose of L-thyroxine in patients with suppressed TSH before pregnancy, in the first, second and, third trimester and after delivery was 154, 154, 164, 160 and 161 micrograms daily, respectively. When the dose had to be changed, the mean increase of the dose was 31.5 micrograms daily. The range of changes in TSH concentration during pregnancy in the patients who have been on suppressive L-thyroxine therapy before conception is quite wide. TSH was adequately suppressed in only 25% of pregnancies. The dose of L-thyroxine in patients with suppressed TSH in the first, second and third trimester was 154, 164 and 160 micrograms daily, respectively

Thyroxin hormone suppression treatment

International Nuclear Information System (INIS)

Samuel, A.M.

1999-01-01

One of the important modalities of treatment of thyroid cancer (TC) after surgery is the administration of thyroxin as an adjuvant treatment. The analysis supports the theory that thyroid suppression plays an important role in patient management. 300 μg of thyroxin, as this is an adequate dose for suppression is given. Ideally the dose should be tailored by testing s-TSH levels. However, since a large number of the patients come from out station cities and villages this is impractical. We therefore depend on clinical criteria of hyperthyroid symptoms and adjust the dose. Very few patients need such adjustment

Beyond viral suppression of HIV

DEFF Research Database (Denmark)

Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

2016-01-01

BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation.

Science.gov (United States)

Hamad, Rania; Jayakumar, Calpurnia; Ranganathan, Punithavathi; Mohamed, Riyaz; El-Hamamy, Mahmoud M I; Dessouki, Amina A; Ibrahim, Abdelazim; Ramesh, Ganesan

2015-08-01

Cisplatin is a highly effective chemotherapeutic drug used to treat a wide variety of solid tumors. However, its use was limited due its dose-limiting toxicity to the kidney. Currently, there are no therapies available to treat or prevent cisplatin nephrotoxicity. Honey is a naturally occurring complex liquid and widely used in traditional Ayurvedic medicine to treat many illnesses. However, its effect on cisplatin nephrotoxicity is unknown. To determine the role of honey in cisplatin nephrotoxicity, animals were pretreated orally for a week and then cisplatin was administered. Honey feeding was continued for another 3 days. Our results show that animals with cisplatin-induced kidney dysfunction, as determined by increased serum creatinine, which received honey feeding had less kidney dysfunction. Improved kidney function was associated with better preservation of kidney morphology in honey-treated group as compared to the cisplatin alone-treated group. Interestingly, honey feeding significantly reduced cisplatin-induced tubular epithelial cell death, immune infiltration into the kidney as well as cytokine and chemokine expression and excretion as compared to cisplatin treated animals. Western blot analysis shows that cisplatin-induced increase in phosphorylation of NFkB was completely suppressed with honey feeding. In conclusion, honey feeding protects the kidney against cisplatin nephrotoxicity through suppression of inflammation and NFkB activation. © 2015 Wiley Publishing Asia Pty Ltd.

Literature and art therapy in post-stroke psychological disorders.

Science.gov (United States)

Eum, Yeongcheol; Yim, Jongeun

2015-01-01

Stroke is one of the leading causes of morbidity and long-term disability worldwide, and post-stroke depression (PSD) is a common and serious psychiatric complication of stroke. PSD makes patients have more severe deficits in activities of daily living, a worse functional outcome, more severe cognitive deficits and increased mortality as compared to stroke patients without depression. Therefore, to reduce or prevent mental problems of stroke patients, psychological treatment should be recommended. Literature and art therapy are highly effective psychological treatment for stroke patients. Literature therapy divided into poetry and story therapy is an assistive tool that treats neurosis as well as emotional or behavioral disorders. Poetry can add impression to the lethargic life of a patient with PSD, thereby acting as a natural treatment. Story therapy can change the gloomy psychological state of patients into a bright and healthy story, and therefore can help stroke patients to overcome their emotional disabilities. Art therapy is one form of psychological therapy that can treat depression and anxiety in stroke patients. Stroke patients can express their internal conflicts, emotions, and psychological status through art works or processes and it would be a healing process of mental problems. Music therapy can relieve the suppressed emotions of patients and add vitality to the body, while giving them the energy to share their feelings with others. In conclusion, literature and art therapy can identify the emotional status of patients and serve as a useful auxiliary tool to help stroke patients in their rehabilitation process.

Animal experiments to investigate biological-chemical radiation protection and the therapy of radiolesions

International Nuclear Information System (INIS)

Brueckner, V.

1974-01-01

The influence of a combined therapy of radiation protection agents and erythropoetin on the radiation-induced suppression of erythropoiesis in mice is studied with the aid of the radioiron utilization test. After whole-body irradiation with 500 R, the erythropoietic system is so severely affected that erythropoetin application alone does not yield any results. AET (significant) and Cysteamin (insignificant), on the other hand, protect the bone marrow to a certain degree. The protected bone marrow provides a better base for erythropoetin therapy than the bone marrow of the irradiated and unprotected animals. Compared to the application of radiation protection agents alone, the combined therapy with AET and erythropoetin increases the radioiron incorporation in the erythrocytes by 7.5% while the therapy with Cysteamin and erythropoetin results in a 19.3% increase. In spite of these methods, however, the radioiron incorporation rate of the control animals was not reached. (BSC/AK) [de

Locoregional injection of F-18 radiopharmaceuticals suppresses tumor xenograft growth in rats

Energy Technology Data Exchange (ETDEWEB)

Wong, C -L [The Univ. of Texas M.D. Anderson Cancer Center, Texas (United States)

2004-07-01

The energetic positrons (0.633 Mev) from F-18 dissipate kinetic energies before annihilation to produce two 0.511 Mev photons which also contribute to the radiation absorbed dose to the surroundings. In living organism, the contribution from the positron itself to the surrounding tissues (up to 2 mm) is larger than from the 2 photons. Apoptosis has been reported in rat tumors after systemic injection of F-18 FDG although no growth retardation was noted. This study is designed to exploit the pharmacokinetic advantages of locoregional injection of positron emitters in the suppression of tumor growth in rats. Methods: Groups of Fisher 344 adult female rats were inoculated with rat mammary tumors (100,000 cells) intramuscularly (IM) in the thigh. Locoregional injection with F-18 NaF or F-18 FDG was accomplished in days 3 or 7 with single doses of increasing strengths (0.2 to 3 mCi). Tumor growth rates were noted and compared to control (sham injection with saline). The locoregional distribution and clearance of F-18 were estimated from serial tomograms using a Concord MicroPET (R4) after intramuscular injection of 0.1-0.2 mCi of F-18 NaF or F-18 FDG in groups of triplicate rats. Results: A dose-related pattern of tumor suppression is noted with F-18 FDG, whether treatment occurs in day 3 or 7 after inoculation. Additional experiment of injection of 5 mci of F-18 FDG at day 14 also suppressed the growth of a well-formed tumor. Tumor suppression by F-18 NaF is less obvious and only occurs with high dose (2 mCi). MicroPET images demonstrate that F-18 FDG is retained in the injection site while F-18 NaF dissipates rapidly. Conclusion: Locoregional injection of positron-emitters may be sufficient to suppress tumor growth. The mechanism is likely related to the pharmacokinetic profile of the compound within the tissue. Discussion: Locoregional application of radionuclides may provide feasible alternatives to slow tumor growth or prevent tumor recurrence. The use of

Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.

NARCIS (Netherlands)

Ananworanich, J.; Gorowara, M.; Avihingsanon, A.; Kerr, S.J.; Heesch, N. van; Khongpetch, C.; Uanithirat, A.; Hill, A.; Ruxrungtham, K.; Burger, D.M.

2012-01-01

Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were

Prevalence of low bone mineral density among HIV patients on long-term suppressive antiretroviral therapy in resource limited setting of western India.

Science.gov (United States)

Dravid, Ameet; Kulkarni, Milind; Borkar, Amit; Dhande, Sachin

2014-01-01

Bone mineral density (BMD) assessment in HIV patients is sparsely done in resource limited settings. We conducted a cross-sectional study of BMD amongst HIV patients following up in our clinic from 1 June to 1 December 2013 by performing dual-energy X-ray absorptiometry scan (Lunar Prodigy Advanced DXA System, GE Healthcare) of lumbar spine and hip. Patients on long term (≥12 months), virologically suppressive antiretroviral therapy (ART) were included. Patients who were ART naïve were included as control population. Virologic failures were excluded. Low BMD was defined by WHO T-score criteria (normal: T score ≥-1;osteopenia: T score between -1 and -2.5 SD; osteoporosis: T score ≤-2.5 SD). Baseline risk factors associated with low BMD like age, low BMI, lipoatrophy, diabetes mellitus, current smoking, current alcohol intake, steroid exposure and menopause were recorded. ART-related factors associated with low BMD like ART duration, exposure to tenofovir and exposure to protease inhibitors (PI) were studied. A total of 536 patients (66% males, 496 ART experienced and 40 ART naïve) were included in this analysis. Median age was 42 years, mean BMI 23.35 kg/m(2) and median CD4 count 146 cells/mm(3). All ART experienced patients had plasma viral loadpatients in our cohort is a matter of deep concern due to its association with pathological fractures. Bone mineral loss was seen irrespective of ART used. Association of low BMD with low baseline CD4 count strengthens the case for early ART.

Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

International Nuclear Information System (INIS)

Zheng, Liu; Weilun, Zhang; Minghong, Jiang; Yaxi, Zhang; Shilian, Liu; Yanxin, Liu; Dexian, Zheng

2012-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy

Inhibition of glycogen synthase kinase-3β attenuates glucocorticoid-induced suppression of myogenic differentiation in vitro.

Directory of Open Access Journals (Sweden)

Zhenyu Ma

Full Text Available Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD, the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3β (GSK-3β is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3β, an inactive form of GSK-3β, suggesting that glucocorticoids affect GSK-3β activity. We then investigated whether GSK-3β inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3β: pharmacological inhibition with LiCl and GSK-3β gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3β inhibition attenuated glucocorticoid-induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3β in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3β may be a strategy for preventing glucocorticoid-induced muscle degeneration.

Suppressive effect of AMP-activated protein kinase on the epithelial-mesenchymal transition in retinal pigment epithelial cells.

Directory of Open Access Journals (Sweden)

Ryo Matoba

Full Text Available The epithelial-mesenchymal transition (EMT in retinal pigment epithelial (RPE cells plays a central role in the development of proliferative vitreoretinopathy (PVR. The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF-α (10 ng/ml and transforming growth factor (TGF-β2 (5 ng/ml. 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, a potent activator of AMPK, significantly suppressed TNF-α and TGF-β2-induced cellular aggregate formation (p < 0.01. Dipyridamole almost completely reversed the suppressive effect of AICAR, whereas 5'-amino-5'-deoxyadenosine restored aggregate formation by approximately 50%. AICAR suppressed the downregulation of E-cadherin and the upregulation of fibronectin and α-smooth muscle actin by TNF-α and TGF-β2. The levels of matrix metalloproteinase (MMP-2, MMP-9, interleukin-6, and vascular endothelial growth factor were significantly decreased by AICAR. Activation of the mitogen-activated protein kinase and mammalian target of rapamycin pathways, but not the Smad pathway, was inhibited by AICAR. These findings indicate that AICAR suppresses the EMT in RPE cells at least partially via activation of AMPK. AMPK is a potential target molecule for the prevention and treatment of PVR, so AICAR may be a promising candidate for PVR therapy.

Social hierarchy and depression: the role of emotion suppression.

Science.gov (United States)

Langner, Carrie A; Epel, Elissa S; Matthews, Karen A; Moskowitz, Judith T; Adler, Nancy E

2012-01-01

Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The coronary artery risk development in young adults [CARDIA] study; Cutter et al., 1991). Much as in study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression.

The clinical impact of immunodeficiency and viraemia in the era of combined antiretroviral therapy for HIV-1 infection

NARCIS (Netherlands)

Zhang, S.

2015-01-01

Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal. We studied the characteristics of episodes of

Disease Suppressive Soils: New Insights from the Soil Microbiome.

Science.gov (United States)

Schlatter, Daniel; Kinkel, Linda; Thomashow, Linda; Weller, David; Paulitz, Timothy

2017-11-01

Soils suppressive to soilborne pathogens have been identified worldwide for almost 60 years and attributed mainly to suppressive or antagonistic microorganisms. Rather than identifying, testing and applying potential biocontrol agents in an inundative fashion, research into suppressive soils has attempted to understand how indigenous microbiomes can reduce disease, even in the presence of the pathogen, susceptible host, and favorable environment. Recent advances in next-generation sequencing of microbiomes have provided new tools to reexamine and further characterize the nature of these soils. Two general types of suppression have been described: specific and general suppression, and theories have been developed around these two models. In this review, we will present three examples of currently-studied model systems with features representative of specific and general suppressiveness: suppression to take-all (Gaeumannomyces graminis var. tritici), Rhizoctonia bare patch of wheat (Rhizoctonia solani AG-8), and Streptomyces. To compare and contrast the two models of general versus specific suppression, we propose a number of hypotheses about the nature and ecology of microbial populations and communities of suppressive soils. We outline the potential and limitations of new molecular techniques that can provide novel ways of testing these hypotheses. Finally, we consider how this greater understanding of the phytobiome can facilitate sustainable disease management in agriculture by harnessing the potential of indigenous soil microbes.

The Use of Virtual Reality in Craving Assessment and Cue-Exposure Therapy in Substance Use Disorders

Science.gov (United States)

Hone-Blanchet, Antoine; Wensing, Tobias; Fecteau, Shirley

2014-01-01

Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs) and a predictive factor of relapse. Various methods to study craving exist; however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse. Current behavioral therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving. They facilitate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioral training especially in real social and environmental contexts with peer pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality (VR) is gaining interest in the development of cue-reactivity paradigms and practices new skills in treatment. VR enhances ecological validity of traditional craving-induction measurement. In this review, we discuss results from (1) studies using VR and alternative virtual agents in the induction of craving and (2) studies combining cue-exposure therapy with VR in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interactions that are associated with drug-seeking behaviors and peer pressure. Findings indicate that VR can successfully increase craving. Studies combining cue–exposure therapy with virtual environment, however, reported mitigated success so far. PMID:25368571

The use of virtual reality in craving assessment and cue-exposure therapy in substance use disorders

Directory of Open Access Journals (Sweden)

Antoine eHone-Blanchet

2014-10-01

Full Text Available Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs and a predictive factor of relapse. Various methods to study craving exist, however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse.Current behavioural therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving. They facilitate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioural training especially in real social and environmental contexts with peer-pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality is gaining interest in the development of cue-reactivity paradigms and practice new skills in treatment. Virtual reality enhances ecological validity of traditional craving induction measurement. In this review, we discuss results from 1 studies using virtual reality and alternative virtual agents in the induction of craving and 2 studies combining cue-exposure therapy with virtual reality in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interactions that are associated with drug seeking behaviours and peer pressure.Findings indicate that virtual reality can successfully increase craving. Studies combining cue exposure-therapy with virtual environment however reported mitigated success so far.

The Effectiveness of Dialectical Behavior Therapy Skills Training Group Vs. Cognitive Therapy Group on Reducing Depression and Suicide Attempts for Borderline Personality Disorder in Taiwan.

Science.gov (United States)

Lin, Tsung-Jen; Ko, Huei-Chen; Wu, Jo Yung-Wei; Oei, Tian Po; Lane, Hsien-Yuan; Chen, Chung-Hey

2018-03-12

Effectiveness of the condensed Dialectical Behavior Therapy Skills Training Group (DBTSTG) was compared to the Cognitive Therapy Group (CTG) in reducing depression and suicide reattempt, and modifying emotion regulation strategies among those with borderline personality disorder (BPD). Eighty-two depressed BPD college students with a suicidal history within the past six-months were randomly allocated to DBTSTG or CTG. Both groups had similar reductions in suicide reattempts and depression after the intervention and 6-month follow-ups. However, the CTG showed improvements in cognitive errors, but the DBTSTG revealed increases in acceptance and decreases in suppression scores. Both groups were effective in decreasing depression and suicide reattempt in BPD college students, probably through increasing adaptive antecedent-focused or response-focused strategies of emotion regulation, respectively.

anti-retroviral therapy related liver injury (arli): a series of 11 cases

African Journals Online (AJOL)

2013-12-02

Dec 2, 2013 ... liver function tests as evidenced by the normal AST and ALT. ... test (RPHA) method. Intervention: The ..... Harris M., Montaner- J.S.G. Clinical use of non- nucleoside ... De Maat M., Mathot R., Veldkamp A., Huitma A.,. Mulder J.

Venture capital: States suffer as suppression expenses climb

Science.gov (United States)

Krista Gebert

2008-01-01

The high cost of suppressing wildfires is taking a toll on federal and state agencies alike. Large wildland fires are complex, costly events influenced by a vast array of physical, climatic, and social factors. During five of the last eight years, the Forest Services' wildfire suppression expenditures have topped $1 billion, and total federal wildland suppression...