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Sample records for reversible severe combined

  1. Combining or Separating Forward and Reverse Logistics

    DEFF Research Database (Denmark)

    Herbert-Hansen, Zaza Nadja Lee; Larsen, Samuel; Nielsen, Anders

    2017-01-01

    Purpose – While forward logistics handles and manages the flow of goods downstream in the supply chain from suppliers to customers, reverse logistics (RL) manages the flow of returned goods upstream. A firm can combine reverse logistics with forward logistics, keep the flows separated, or choose......-research addresses intra-RL issues while the relationship between forward and reverse logistics is under-researched. This paper contributes to RL-theory by identifying the contextual factors that determine the most advantageous relationship between forward and reverse logistics, and proposes a novel decision making...

  2. Acute reversible Charles Bonnet syndrome precipitated by sudden severe anemia.

    Science.gov (United States)

    Kaeser, Pierre-Francois; Borruat, Francois-Xavier

    2009-01-01

    To report the sudden onset of reversible Charles Bonnet syndrome precipitated byacute severe anemia. The charts of three patients (Usher syndrome, bilateral macular degeneration, and bilateral retinal vein occlusion) with acute Charles Bonnet syndrome in the setting of severe anemia were reviewed. Anemia resulted from bladder surgery, recto-colitis, and severe urinary tract infection. Hemoglobin ranged from 78 to 86 g/L. Decreased visual acuity and formed visual hallucinations (giants, flowers, animals) were present in all three patients. Rapid reversal of Charles Bonnet syndrome and visual acuity improvement followed blood transfusion. Acute severe anemia can precipitate Charles Bonnet syndrome, which may be reversible by blood transfusion.

  3. Learning about Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    Skip to main content Learning About Severe Combined Immunodeficiency (SCID) Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding ...

  4. Reversal of a Severe Case of Self-Mutilation

    Science.gov (United States)

    Muttar, A. K.; And Others

    1975-01-01

    A particularly severe case of self-injurious behavior in a multiply (visually, mentally, and emotionally) handicapped 10-year-old girl was successfully treated by response contingent shock, combined with rewards. (DB)

  5. Determinants of recovery from severe posterior reversible encephalopathy syndrome.

    Directory of Open Access Journals (Sweden)

    Stephane Legriel

    Full Text Available OBJECTIVE: Few outcome data are available about posterior reversible encephalopathy syndrome (PRES. We studied 90-day functional outcomes and their determinants in patients with severe PRES. DESIGN: 70 patients with severe PRES admitted to 24 ICUs in 2001-2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS of 5 (good recovery on day 90. MAIN RESULTS: Consciousness impairment was the most common clinical sign, occurring in 66 (94% patients. Clinical seizures occurred in 57 (81% patients. Median mean arterial pressure was 122 (105-143 mmHg on scene. Cerebral imaging abnormalities were bilateral (93% and predominated in the parietal (93% and occipital (86% white matter. Median number of brain areas involved was 4 (3-5. Imaging abnormalities resolved in 43 (88% patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14% patients. The most common causes were drug toxicity (44% and hypertensive encephalopathy (41%. On day 90, 11 (16% patients had died, 26 (37% had marked functional impairments (GOS, 2 to 4, and 33 (56% had a good recovery (GOS, 5. Factors independently associated with GOS<5 were highest glycaemia on day 1 (OR, 1.22; 95%CI, 1.02-1.45, p = 0.03 and time to causative-factor control (OR, 3.3; 95%CI, 1.04-10.46, p = 0.04, whereas GOS = 5 was associated with toxaemia of pregnancy (preeclampsia/eclampsia (OR, 0.06; 95%CI, 0.01-0.38, p = 0.003. CONCLUSIONS: By day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.

  6. Reversible cognitive, motor, and driving impairments in severe hypothyroidism.

    Science.gov (United States)

    Smith, Charles D; Grondin, Richard; LeMaster, William; Martin, Barbara; Gold, Brian T; Ain, Kenneth B

    2015-01-01

    Hypothyroidism has been associated with cognitive and motor impairments that are likely to constitute hazards in the operation of motor vehicles and a public safety risk. However, there is a paucity of data that would provide an evidence basis for recommendations to hypothyroid patients. The purpose of this study was to determine the specific neurological and psychological deficits consequent to hypothyroidism and whether they are of sufficient magnitude to impede the safe operation of motor vehicles. Repeated measurements were obtained in euthyroid, hypothyroid, and euthyroid hormone replaced states of thyroid cancer outpatients, at an academic medical center, who underwent thyroid hormone withdrawal preparation for radioiodine scanning. Study design used a within-subjects longitudinal "A-B-A" with each subject tested at three visits in the same sequence: euthyroid, hypothyroid, and euthyroid for a total of 32 subjects. Data on clinical status and cognitive performance were collected using standard instruments, including ThyDQoL and ThySRQ measures, National Adult Reading Test, Boston Naming Test, Mini-Mental State Exam, Wechsler Adult Intelligence Test-Revised, Letter Fluency FAS, and Beck Depression Inventory. Fine-motor function was measured with an automated assessment panel, and driving performance on a commercial driving simulator. In severe hypothyroidism (median thyrotropin 83.2 mIU/L), fine-motor performance of hands and reaction times in emergency braking tests were slowed, as well as subjective slowing reported on structured clinical scales. Depression was present, typified by vegetative and mood alterations, but lacking reported guilt and lowered self-esteem seen in other types of depression. Cognitive impairment was characterized by declines on speeded executive tests. In contrast, episodic memory performance improved over time regardless of thyroid hormone status. Braking times increased in hypothyroidism by 8.5%, equivalent to reports of effects

  7. Posterior reversible encephalopathy syndrome in patient of severe ...

    African Journals Online (AJOL)

    neuroradiologic condition, not commonly reported in the literature. PRES is an uncommon complication of severe preeclampsia/eclampsia. We report the management of one patient with postpartum preeclampsia as an association of HELLP syndrome ...

  8. Novel combination of reverse engineering and vapid prototyping in medicine

    CSIR Research Space (South Africa)

    Schenker, R

    1999-08-01

    Full Text Available The technologies of reverse engineering and rapid prototyping are emerging as useful new tools in medicine. One application is of particular interest in orthopaedic, dental and reconstructive surgery. It involves the imaging, modelling...

  9. Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia.

    Directory of Open Access Journals (Sweden)

    Abbie Chapman Johnson

    Full Text Available Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO4 is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB disruption and neuroinflammation that lowers seizure threshold. Further, MgSO4 decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP was combined with a high cholesterol diet (HC to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg required to elicit seizure in RUPP + HC ± MgSO4 and compared to normal pregnant controls (n = 6/group; gestational day 20. RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼ 65% lower vs. control (12.4 ± 1.7 vs. 36.7 ± 3.9 mg/kg PTZ; p<0.05 that was reversed by MgSO4 (45.7 ± 8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC. BBB permeability to sodium fluorescein, measured in-vivo (n = 5-7/group, was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9 ± 1.0 vs. 12.2 ± 0.3 counts/gram ×1000; p<0.05 and was unaffected by MgSO4 (15.6 ± 1.0 counts/gram ×1000; p<0.05 vs. controls. In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35 ± 2% of microglia being active compared to 9 ± 2% in normal pregnancy (p<0.01; n = 3-8/group. MgSO4 treatment reversed neuroinflammation, reducing microglial activation to 6 ± 2% (p<0.01 vs. RUPP+HC. Overall, RUPP+HC rats were in a state of augmented

  10. Long term combination treatment for severe idiopathic pulmonary arterial hypertension

    Science.gov (United States)

    Affuso, Flora; Cirillo, Plinio; Ruvolo, Antonio; Carlomagno, Guido; Fazio, Serafino

    2010-01-01

    We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event. PMID:21160759

  11. Severe Postpartum Headache and Hypertension Caused by Reversible Cerebral Vasoconstriction Syndrome: A Case Report.

    Science.gov (United States)

    McIlroy, Ed; Sethuraman, Rajamani; Woograsingh, Reshma; Nelson-Piercy, Catherine; Gilbert-Kawai, Edward

    2017-07-10

    Reversible cerebrovascular vasoconstriction syndrome is an uncommon condition that presents as severe headache and hypertension. Recent literature suggests a 1% incidence in postpartum headache cases. It can cause subarachnoid hemorrhages, cerebral ischemia, and seizures. It is often misdiagnosed as postdural puncture headache or preeclampsia. In this case, a postpartum woman, who had received epidural anesthesia for labor, presented 5 days postpartum with severe headache that did not resolve with an epidural blood patch. She then became more hypertensive and suffered a grand mal seizure. When treatment for eclampsia failed to resolve her symptoms, magnetic resonance angiography was performed. It demonstrated the pathognomic signs of reversible cerebrovascular vasoconstriction syndrome. Her symptoms resolved with nimodipine.

  12. Posterior reversible leukoencephalopathy syndrome (PRES) associated with severe eclampsia: Clinical and biochemical features.

    Science.gov (United States)

    Camara-Lemarroy, Carlos R; Escobedo-Zúñiga, Nicolás; Villarreal-Garza, Estefania; García-Valadez, Erick; Góngora-Rivera, Fernando; Villarreal-Velázquez, Héctor J

    2017-01-01

    Posterior Reversible Encephalopathy Syndrome (PRES) and eclampsia share clinical characteristics and patients may present with a combination of these two entities. Our aim was to study the proportion of patients with eclampsia having evidence of PRES in their brain imaging. Retrospective study of pregnant patients diagnosed as having eclampsia that underwent brain magnetic resonance imaging (MRI) during their hospitalization. MRI diagnosis of PRES was assessed by 2 investigators blinded to group. We included a total of 29 patients with eclampsia, out of which 17 (58.6%) had MRI evidence of PRES. When patients with eclampsia and eclampsia/PRES were compared, there was no difference in demographic characteristics such as age, weight or multiparity. Patients with eclampsia/PRES had higher levels of creatinine, liver enzymes, mean platelet volume and there was a trend towards higher proteinuria. Infants of mothers with eclampsia/PRES also had worse 1min APGAR scores. PRES appears to accompany eclampsia in over half of all cases. The clinical picture of patients with eclampsia with or without associated PRES is similar, but certain biochemical characteristics suggest that PRES might be indicative of a more severe disease process. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  13. Combined Reverse-Brayton Joule Thompson Hydrogen Liquefaction Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Shimko, Martin A. [Gas Equipment Engineering Corporation, Milford, CT (United States); Dunn, Paul M. [Gas Equipment Engineering Corporation, Milford, CT (United States)

    2011-12-31

    The following is a compilation of Annual Progress Reports submitted to the DOE’s Fuel Cell Technologies Office by Gas Equipment Engineering Corp. for contract DE-FG36-05GO15021. The reports cover the project activities from August 2005 through June 2010. The purpose of this project is to produce a pilot-scale liquefaction plant that demonstrates GEECO’s ability to meet or exceed the efficiency targets set by the DOE. This plant will be used as a model to commercialize this technology for use in the distribution infrastructure of hydrogen fuel. It could also be applied to markets distributing hydrogen for industrial gas applications. Extensive modeling of plant performance will be used in the early part of the project to identify the liquefaction cycle architecture that optimizes the twin goals of increased efficiency and reduced cost. The major challenge of the project is to optimize/balance the performance (efficiency) of the plant against the cost of the plant so that the fully amortized cost of liquefying hydrogen meets the aggressive goals set by DOE. This project will design and build a small-scale pilot plant (several hundred kg/day) that will be both a hardware demonstration and a model for scaling to larger plant sizes (>50,000 kg/day). Though an effort will be made to use commercial or near-commercial components, key components that will need development for either a pilot- or full-scale plant will be identified. Prior to starting pilot plant fabrication, these components will be demonstrated at the appropriate scale to demonstrate sufficient performance for use in the pilot plant and the potential to achieve the performance used in modeling the full-scale plant.

  14. Gene Therapy for RAG-deficient Severe Combined Immunodeficiency

    NARCIS (Netherlands)

    K. Pike (Karin)

    2007-01-01

    textabstractSevere combined immunodeficiency (SCID) is a rare class of primary, inherited, immunodeficiency causing infants to suffer from persistent diarrhea, opportunistic infections and a failure to thrive. RAG proteins play a crucial role in the initiation of V(D)J recombination of

  15. Posterior Reversible Encephalopathy Syndrome in severe preeclampsia: case report and literature review

    OpenAIRE

    AYGÜN, Banu KUMBAK; Baykuş, Yakup; Berilgen, Said; Kavak, Burçin; Çelik, Hüsnü; GÜRATEŞ, Bilgin

    2010-01-01

    We describe a 23 year old primigravid patient with severe preeclampsia complicated by posterior reversible encephalopathy syndrome (PRES), who presented with sensory and motor deficits and amnesia in the postpartum period Cranial magnetic resonance imaging (MRI) showed abnormal areas in the white matter of bilateral parieto-occipital lobes, indicating brain edema which disappeared completely on the follow-up scan taken four weeks after delivery together with complete symptom regression. The d...

  16. Hip-inspired implant for revision of failed reverse shoulder arthroplasty with severe glenoid bone loss

    OpenAIRE

    Uri, Ofir; Bayley, Ian; Lambert, Simon

    2014-01-01

    Background and purpose Glenoid reconstruction and inverted glenoid re-implantation is strongly advocated in revisions of failed reverse shoulder arthroplasty (RSA). Nevertheless, severe glenoid deficiency may preclude glenoid reconstruction and may dictate less favorable solutions, such as conversion to hemiarthropasty or resection arthropasty. The CAD/CAM shoulder (Stanmore Implants, Elstree, UK), a hip arthroplasty-inspired implant, may facilitate glenoid component fixation in these challen...

  17. Successful nonsibling bone marrow transplantation in severe combined immunodeficiency

    DEFF Research Database (Denmark)

    Ramsøe, K; Skinhøj, P; Andersen, V

    1978-01-01

    Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA-A a......A); tests of cell-mediated immunity are normal. Apart from slight upper respiratory infections, the patient has been healthy. Physical and psychological development have been normal....

  18. Gene recognition by combination of several gene-finding programs.

    Science.gov (United States)

    Murakami, K; Takagi, T

    1998-01-01

    A number of programs have been developed to predict the eukaryotic gene structures in DNA sequences. However, gene finding is still a challenging problem. We have explored the effectiveness when the results of several gene-finding programs were re-analyzed and combined. We studied several methods with four programs (FEXH, GeneParser3, GEN-SCAN and GRAIL2). By HIGHEST-policy combination method or BOUNDARY method, approximate correlation (AC) improved by 3-5% in comparison with the best single gene-finding program. From another viewpoint, OR-based combination of the four programs is the most reliable to know whether a candidate exon overlaps with the real exon or not, although it is less sensitive than GENSCAN for exon-intron boundaries. Our methods can easily be extended to combine other programs. We have developed a server program (Shirokane System) and a client program (GeneScope) to use the methods. GeneScope is available through a WWW site (http://gf.genome.ad.jp/). (katsu,takagi)@ims.u-tokyo.ac.jp

  19. Unexpectedly large enhancement of a severely constricted field with reversed Galilean telescopes.

    Science.gov (United States)

    Campbell, M C; Ellison, P J; Strong, J G; Lovasik, J V

    1989-04-01

    A 25-year-old female presented with severely constricted visual fields secondary to stroke associated with mitral valve prolapse. Repeatably measured central fields of less than 4 degrees diameter showed an unexpected enlargement up to 20 to 40 degrees diameter, when fitted with reversed full field 1.3x and 1.7x Galilean telescopes. Although initial tests indicated no psychogenic component, fields of approximately 20 degrees diameter were eventually obtained through an imitation telescope made with 2 plano lenses. This technique may be useful in determining whether there is a psychogenic component to inexplicable field results in other patients.

  20. The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom-Programmable Circuits

    Science.gov (United States)

    2017-03-23

    The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom- Programmable Circuits Raza Shafiq Hamid Mahmoodi Houman Homayoun Hassan... programmable circuits. While functionality of programmable cells are only known to trusted parties, effective techniques for activation and propagation...of the cells are introduced. The ATPG attack carefully studies dependency of programmable cells to develop their (partial) truth tables. Results

  1. A severe skeletal Class II correction by activator headgear combination

    Directory of Open Access Journals (Sweden)

    Shivam Agrawal

    2016-01-01

    Full Text Available Skeletal Class II malocclusion with mandibular deficiency and maxillary excess is a severe skeletal problem encountered in growing individuals. Correction of mandibular deficiency and maxillary excess in a skeletal Class II patient with a vertical growth pattern poses a great challenge. The control of vertical dimension becomes very important as downward and backward rotation of mandible will exaggerate the facial convexity. The present case signifies the importance of functional jaw orthopedic treatment in a vertically growing female patient with mandibular deficiency and maxillary vertical excess. Activator headgear combination was used for skeletal correction which was followed by fixed mechanotherapy. Superimposition of pretreatment and posttreatment cephalometric tracings shows desired treatment outcomes.

  2. Combination of several algorithms while solving the forecasting problem

    Directory of Open Access Journals (Sweden)

    Chumachenko O.I.

    2016-04-01

    Full Text Available The forecasting problem is undoubtedly one of the most important for humanity, but also it is standing next to the most difficult ones because there is no guarantee that the predicted process behavior will not change dramatically in the future. The aim of the paper is to develop a new forecasting method that uses an approach of several models combining and test its quality on a set of test data. For this purpose, the main existing forecasting methods were considered, such as artificial neural networks, group method of data handling and linear regression. For the combination of forecasting models the bagging approach was chosen. The proposed method was implemented in a software environment Matlab and tested (along with several existing methods on 11 sets of test data. The fact that among the methods that were tested, the proposed one showed the best results, indicating the possibility of its successful application in practice is a scientific novelty and practical significance of the article.

  3. Genistein, a soy phytoestrogen, reverses severe pulmonary hypertension and prevents right heart failure in rats.

    Science.gov (United States)

    Matori, Humann; Umar, Soban; Nadadur, Rangarajan D; Sharma, Salil; Partow-Navid, Rod; Afkhami, Michelle; Amjedi, Marjan; Eghbali, Mansoureh

    2012-08-01

    Pretreatment with a phytoestrogen genistein has been shown to attenuate the development of pulmonary hypertension (PH). Because PH is not always diagnosed early, we examined whether genistein could also reverse preexisting established PH and prevent associated right heart failure (RHF). PH was induced in male rats by 60 mg/kg of monocrotaline. After 21 days, when PH was well established, rats received daily injection of genistein (1 mg/kg per day) for 10 days or were left untreated to develop RHF by day 30. Effects of genistein on human pulmonary artery smooth muscle cell and endothelial cell proliferation and neonatal rat ventricular myocyte hypertrophy were assessed in vitro. Severe PH was evident 21 days after monocrotaline, as peak systolic right ventricular pressure increased to 66.35±1.03 mm Hg and right ventricular ejection fraction reduced to 41.99±1.27%. PH progressed to RHF by day 30 (right ventricular pressure, 72.41±1.87 mm Hg; RV ejection fraction, 29.25±0.88%), and mortality was ≈75% in RHF rats. Genistein therapy resulted in significant improvement in lung and heart function as right ventricular pressure was significantly reduced to 43.34±4.08 mm Hg and right ventricular ejection fraction was fully restored to 65.67±1.08% similar to control. Genistein reversed PH-induced pulmonary vascular remodeling in vivo and inhibited human pulmonary artery smooth muscle cell proliferation by ≈50% in vitro likely through estrogen receptor-β. Genistein also reversed right ventricular hypertrophy (right ventricular hypertrophy index, 0.35±0.029 versus 0.70±0.080 in RHF), inhibited neonatal rat ventricular myocyte hypertrophy, and restored PH-induced loss of capillaries in the right ventricle. These improvements in cardiopulmonary function and structure resulted in 100% survival by day 30. Genistein restored PH-induced downregulation of estrogen receptor-β expression in the right ventricle and lung. In conclusion, genistein therapy not only rescues

  4. Maraviroc and reverse transcriptase inhibitors combinations as potential preexposure prophylaxis candidates.

    Science.gov (United States)

    Herrera, Carolina; Armanasco, Naomi; García-Pérez, Javier; Ziprin, Paul; Olejniczak, Natalia; Alcamí, José; Nuttall, Jeremy; Shattock, Robin J

    2016-04-24

    Receptive anal intercourse in both men and women is associated with the highest probability for sexual acquisition of HIV infection. As part of a program to develop an effective prevention strategy, we performed an ex-vivo preclinical evaluation to determine the efficacy of multiple double combinations of maraviroc (MVC) and reverse transcriptase inhibitors (RTIs). The entry inhibitor, MVC, a nucleotide RTI, tenofovir and two non-nucleoside RTIs, UC781 and TMC120 (dapivirine, DPV), were used in double, combinations against a panel of CCR5-using clade B and clade C HIV-1 isolates and against MVC-escape variants. A gel-formulated version of MVC-DPV combination was also tested. Indicator cells, cocultures of immature dendritic cells with CD4T cells, and colorectal tissue explants were used to assess antiviral activity of drug combinations. All dual MVC-RTI combinations tested inhibited MVC-sensitive and resistant isolates in cellular and colorectal explants models. All the combinations were positive with no reduction in the activity of MVC. In tissue explants, the combinations against all viral isolates tested produced an increase in the activity of MVC. An initial gel-formulation of MVC-DPV combination showed greater and prolonged antiviral activity of MVC in mucosal tissue explants. This study demonstrates that combinations based on antiretroviral drugs inhibiting HIV transmission at viral entry and reverse transcription have potential as prevention strategies against colorectal transmission of HIV-1 including MVC-resistant isolates. Preclinical evaluation with colorectal tissue explants indicates that a gel-formulation of MVC-DPV is an effective candidate colorectal microbicide.

  5. Separate and Concentrate Lactic Acid Using Combination of Nanofiltration and Reverse Osmosis Membranes

    Science.gov (United States)

    Li, Yebo; Shahbazi, Abolghasem; Williams, Karen; Wan, Caixia

    The processes of lactic acid production include two key stages, which are (a) fermentation and (b) product recovery. In this study, free cell of Bifidobacterium longum was used to produce lactic acid from cheese whey. The produced lactic acid was then separated and purified from the fermentation broth using combination of nanofiltration and reverse osmosis membranes. Nanofiltration membrane with a molecular weight cutoff of 100-400 Da was used to separate lactic acid from lactose and cells in the cheese whey fermentation broth in the first step. The obtained permeate from the above nanofiltration is mainly composed of lactic acid and water, which was then concentrated with a reverse osmosis membrane in the second step. Among the tested nanofiltration membranes, HL membrane from GE Osmonics has the highest lactose retention (97±1%). In the reverse osmosis process, the ADF membrane could retain 100% of lactic acid to obtain permeate with water only. The effect of membrane and pressure on permeate flux and retention of lactose/lactic acid was also reported in this paper.

  6. Reversal of Jaundice in Two Patients with Inoperable Cholangiocarcinoma Treated with Cisplatin and Gemcitabine Combination

    Directory of Open Access Journals (Sweden)

    Maarten Criel

    2012-01-01

    Full Text Available Two patients are presented with severe jaundice, due to inoperable cholangiocarcinoma. The chemotherapeutic approach in patients with severe jaundice is discussed. Many schedules of chemotherapy were developed in this tumor type with normal serum bilirubin. We report here the first successful use of cisplatin and gemcitabine combination chemotherapy in these patients. Tolerability was good and liver function tests gradually improved.

  7. Combination therapy for inhibitor reversal in haemophilia A using monoclonal anti-CD20 and rapamycin.

    Science.gov (United States)

    Biswas, Moanaro; Rogers, Geoffrey L; Sherman, Alexandra; Byrne, Barry J; Markusic, David M; Jiang, Haiyan; Herzog, Roland W

    2017-01-05

    Development of antibodies (inhibitors) against coagulation factor VIII (FVIII) is a major complication of intravenous replacement therapy in haemophilia A (HA). Current immune tolerance induction (ITI) regimens are not universally effective. Rituximab, a B cell-depleting antibody against CD20, has shown mixed results for inhibitor reversal in patients. This study aims to develop a combinatorial therapy for inhibitor reversal in HA, using anti-murine CD20 (anti-mCD20) antibody and rapamycin, which targets both B and T cell responses. Additionally, it extensively characterises the role of the IgG backbone in B cell depletion by anti-CD20 antibodies. For this, inhibitors were generated in BALB/c-HA mice by weekly IV injection of FVIII. Subsequently, anti-mCD20 (18B12) with IgG2a or IgG1 backbone was injected IV in two doses three weeks apart and B cell depletion and recovery was characterised. Rapamycin was administered orally 3x/week (for 1 month) while continuing FVIII injections. Altering the IgG backbone of anti-mCD20 from IgG2a to IgG1 reduced overall depletion of B cells (including memory B cells), and marginal zone, B-10, and B-1b cells were specifically unaffected. While neither antibody was effective alone, in combination with rapamycin, anti-mCD20 IgG2a but not IgG1 was able to reverse inhibitors in HA mice. This regimen was particularly effective for starting titres of ~10 BU. Although IgG1 anti-mCD20 spared potentially tolerogenic B cell subsets, IgG2a directed sustained hyporesponsiveness when administered in conjunction with rapamycin. This regimen represents a promising treatment for inhibitor reversal in HA, as both of these compounds have been extensively used in human patients.

  8. Hip-inspired implant for revision of failed reverse shoulder arthroplasty with severe glenoid bone loss

    Science.gov (United States)

    2014-01-01

    Background and purpose Glenoid reconstruction and inverted glenoid re-implantation is strongly advocated in revisions of failed reverse shoulder arthroplasty (RSA). Nevertheless, severe glenoid deficiency may preclude glenoid reconstruction and may dictate less favorable solutions, such as conversion to hemiarthropasty or resection arthropasty. The CAD/CAM shoulder (Stanmore Implants, Elstree, UK), a hip arthroplasty-inspired implant, may facilitate glenoid component fixation in these challenging revisions where glenoid reconstruction is not feasible. We questioned (1) whether revision arthroplasty with the CAD/CAM shoulder would alleviate pain and improve shoulder function in patients with failed RSA, not amenable to glenoid reconstruction, (2) whether the CAD/CAM hip-inspired glenoid shell would enable secure and durable glenoid component fixation in these challenging revisions. Patients and methods 11 patients with failed RSAs and unreconstructable glenoids underwent revision with the CAD/CAM shoulder and were followed-up for mean 35 (28–42) months. Clinical outcomes included the Oxford shoulder score, subjective shoulder value, pain rating, physical examination, and shoulder radiographs. Results The average Oxford shoulder score and subjective shoulder value improved statistically significantly after the revision from 50 to 33 points and from 17% to 48% respectively. Pain rating at rest and during activity improved significantly from 5.3 to 2.3 and from 8.1 to 3.8 respectively. Active forward flexion increased from 25 to 54 degrees and external rotation increased from 9 to 21 degrees. 4 patients required reoperation for postoperative complications. No cases of glenoid loosening occurred. Interpretation The CAD/CAM shoulder offers an alternative solution for the treatment of failed RSA that is not amenable to glenoid reconstruction. PMID:24650026

  9. Perfect quantum state engineering by the combination of the counterdiabatic driving and the reverse-engineering technique

    Science.gov (United States)

    Wu, Qi-Cheng; Huang, Bi-Hua; Chen, Ye-Hong; Shi, Zhi-Cheng; Song, Jie; Xia, Yan

    2017-10-01

    We propose a method to design shortcuts to adiabaticity for implementing perfect quantum state engineering by the combination of the counterdiabatic driving and the reverse engineering technique. Based on the method, we can design simple schemes to realize the intended dynamics. For the sake of clearness, we apply this method to several examples including two-level, three-level and four-level system. We show that fast quantum state engineering can be realized by utilizing simply-designed auxiliary Hamiltonian. Furthermore, a suitable choice of the control parameters can eliminate the additional couplings in the introduced auxiliary Hamiltonian. Numerical simulation reveals that the constructed scheme is reliable and robust against various dissipation effects and the fluctuations of control parameters in current technology.

  10. The role of biomarkers in dilated cardiomyopathy: Assessment of clinical severity and reverse remodeling.

    Science.gov (United States)

    Amorim, Sandra; Campelo, Manuel; Moura, Brenda; Martins, Elisabete; Rodrigues, João; Barroso, Isaac; Faria, Margarida; Guimarães, Tiago; Macedo, Filipe; Silva-Cardoso, José; Maciel, Maria Júlia

    2017-10-05

    Biomarkers in dilated cardiomyopathy (DCM) reflect various pathobiological processes, including neurohormonal activation, oxidative stress, matrix remodeling, myocyte injury and myocyte stretch. We assessed the role of biomarkers in clinical and echocardiographic parameters and in left ventricular (LV) reverse remodeling (LVRR). In this prospective study of 50 DCM patients (28 men, aged 59±10 years) with LV ejection fraction (LVEF) 10 U in LVEF after optimal medical therapy. Baseline LVEF was 25.4±9.8% and LV end-diastolic diameter (LVEDD)/body surface area (BSA) was 34.2±4.5 mm/m(2). LVRR occurred in 34% of patients within 17.6±15.6 months. No correlation was found between B-type natriuretic peptide (BNP), 25-hydroxyvitamin D (25(OH)D), CA-125, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) [Lp(a)], noradrenaline, adrenaline, renin or aldosterone and LVRR. Patients in NYHA class III or IV, with pulmonary congestion or ankle edema, had higher CA-125, cystatin C, BNP and hs-CRP levels (p<0.05). CA-125 was correlated with BNP (r=0.61), hs-CRP (r=0.56) and uric acid (r=0.52) (all p=0.01). BNP correlated directly with LVEDD (r=0.49), LV volumes (r=0.51), pulmonary artery systolic pressure (PASP) (r=0.43) and E/e' (r=0.31), and was inversely correlated with LVEF (r=-0.50) and e' velocity (r=-0.32) (p<0.05). CA-125 was positively correlated with left atrial volume/BSA (r=0.46), E/A ratio (r=0.60) and PASP (r=0.49) (p<0.05). No correlation was found between biomarkers and LVRR, but CA-125, BNP and hs-CRP were predictors of clinical severity and congestion. BNP correlated with parameters of systolic and diastolic dysfunction, while CA-125 correlated with measures of diastolic dysfunction. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Comparison and combination of several MeSH indexing approaches.

    Science.gov (United States)

    Yepes, Antonio Jose Jimeno; Mork, James G; Demner-Fushman, Dina; Aronson, Alan R

    2013-01-01

    MeSH indexing of MEDLINE is becoming a more difficult task for the group of highly qualified indexing staff at the US National Library of Medicine, due to the large yearly growth of MEDLINE and the increasing size of MeSH. Since 2002, this task has been assisted by the Medical Text Indexer or MTI program. We extend previous machine learning analysis by adding a more diverse set of MeSH headings targeting examples where MTI has been shown to perform poorly. Machine learning algorithms exceed MTI's performance on MeSH headings that are used very frequently and headings for which the indexing frequency is very low. We find that when we combine the MTI suggestions and the prediction of the learning algorithms, the performance improves compared to any single method for most of the evaluated MeSH headings.

  12. Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Werner Wunderli

    Full Text Available Infants with severe primary combined immunodeficiency (SCID and children post-allogeneic hematopoietic stem cell transplantation (HSCT are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.

  13. Successful combined approach to a severe Fournier′s gangrene

    Directory of Open Access Journals (Sweden)

    Tommaso Agostini

    2014-01-01

    Full Text Available We present a case of a successful reconstruction of a severe Fournier′s gangrene (FG involving the scrotum, the perineum, the right ischial area and extended to the lower abdomen. There are many different surgical techniques to repair and reconstruct the defect following debridement in FG. The authors treated this complex wound using negative pressure wound therapy (NPWT, dermal regeneration template and a split-thickness skin graft. Complete recovery was achieved and no major complications were observed. The patient showed a satisfying functional and aesthetic result.

  14. A Combined Approach to Severe Multi-Organ Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Habibollah Saadat

    2009-03-01

    Full Text Available Severe coronary artery disease often coexists with peripheral vascular atherosclerosis. The assessment of the supra-aortic circulation is, therefore, of clinical relevance. We herein describe a case of coronary artery disease treated with surgical revascularization using the internal mammary artery and thereafter the progressive atherosclerotic disease of the native coronary arteries as well as the left subclavian and left renal arteries. We also describe and discuss the clinical presentation, the diagnostic procedures, and the therapeutic approach with respect to the percutaneous transluminal angioplasty of the subclavian, renal, and right coronary arteries.

  15. Severe reversible pulmonary hypertension in smoldering multiple myeloma: two cases and review of the literature.

    Science.gov (United States)

    Feyereisn, Wayne L; Fenstad, Eric R; McCully, Robert B; Lacy, Martha Q

    2015-03-01

    An association between pulmonary hypertension (PH) and POEMS syndrome (characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) as well as other plasma cell dyscrasias, including multiple myeloma (MM), has been shown to exist. Recent case reports have identified a reversible form of PH that occurs outside of previously identified etiologies. We report two cases of PH in the setting of smoldering MM (SMM) that resolved with chemotherapy and stem cell transplantation. Although other features were individualized among the cases (dermatomyositis, scleromyxedema), treatment of MM and SMM resulted in a normalization of right ventricular systolic pressure and improvement in right ventricular dysfunction that was previously unresponsive to PH therapies. The magnitude and sustained nature of reversibility in these four cases could offer clues about the pathophysiology and treatment of PH.

  16. Severe cervical glandular cell lesions and severe cervical combined lesions - Predictive value of the Papanicolaou smear

    NARCIS (Netherlands)

    Erp, AJMV; Smedts, FMM; Vooijs, GP

    2004-01-01

    BACKGROUND. The purpose of the current study was to determine the accuracy of routinely screened cervical smears to predict a glandular cell lesion in histologically confirmed cases of cervical adenocarcinoma in situ (AIS), invasive adenocarcinoma (ADCA), adenosquamous carcinoma (ADSQCA), and severe

  17. HPLC/ICP-MS in combination with "reverse" online isotope dilution in drug metabolism studies.

    Science.gov (United States)

    Meermann, Björn; Hulstaert, Anne; Laenen, Aline; Van Looveren, Cis; Vliegen, Maarten; Cuyckens, Filip; Vanhaecke, Frank

    2012-03-06

    During the development of a new drug compound, its metabolism needs to be unraveled. For quantification of the metabolites formed, the drug under investigation is traditionally synthesized with a radiolabel ((14)C or (3)H) and the metabolites present in different matrixes (blood, urine, feces) upon drug administration are determined by means of high-performance liquid chromatography (HPLC) coupled to radiodetection. This approach allows for quantification of the metabolites formed and enables a straightforward distinction between exogenous (i.e., drug-related) and endogenous species (as only the radiolabeled species are detected). However, in some cases, the use of a radiolabeled compound in human in vivo studies is not advisible, e.g., for drug compounds or their metabolites showing a long plasma or tissue half-life. In cases where the candidate drug molecule contains an element detectable by means of inductively coupled plasma mass spectrometry (ICP-MS), HPLC/ICP-MS is a promising alternative approach. However, the method lacks specificity when a distinction between drug-related species and endogenous compounds containing the same target element needs to be accomplished. As a result, we have developed an HPLC/ICP-MS-based method combined with "reverse" online isotope dilution ("reverse" online ID) for metabolite quantification. The methodology was evaluated by the analysis of feces samples from rats dosed with a (81)Br-labeled drug compound. The method allows for both (i) valid quantification of the drug metabolites and (ii) distinction among endogenous, exogenous, and "mixed" species, based on their isotopic "fingerprint". A good repeatability (relative standard deviation of 4.2%) and limit of detection (0.35 mg of drug compound L(-1) of feces extract), of the same order of magnitude as those observed for "normal" online ID HPLC/ICP-MS and HPLC/radiodetection, were achieved.

  18. Cryopreservation of Human Adipose-Derived Stem Cells in Combination with Trehalose and Reversible Electroporation.

    Science.gov (United States)

    Dovgan, Barbara; Barlič, Ariana; Knežević, Miomir; Miklavčič, Damijan

    2017-02-01

    New cryopreservation approaches for medically applicable cells are of great importance in clinical medicine. Current protocols employ the use of dimethyl sulfoxide (DMSO), which is toxic to cells and causes undesirable side effects in patients, such as cardiac arrhythmias, neurological events, and others. Trehalose, a nontoxic disaccharide, has been already studied as a cryoprotectant. However, an efficient approach for loading this impermeable sugar into mammalian cells is missing. In our study, we assessed the efficiency of combining reversible electroporation and trehalose for cryopreservation of human adipose-derived stem cells. First, we determined reversible electroporation threshold by loading of propidium iodide into cells. The highest permeabilization while maintaining high cell viability was reached at 1.5 kV/cm, at 8 pulses, 100 µs, and 1 Hz. Second, cells were incubated in 250 or 400 mM trehalose and electroporated before cryopreservation. After thawing, 83.8 ± 1.8 % (mean ± SE) cell recovery was obtained at 250 mM trehalose. By using a standard freezing protocol (10 % DMSO in 90 % fetal bovine serum), cell survival after thawing was about 91.5 ± 1.6 %. We also evaluated possible effects of electroporation on cells' functionality before and after thawing. Successful cell growth and efficient adipogenic and osteogenic differentiation were achieved. In conclusion, electroporation seems to be an efficient method for loading nonpermeable trehalose into human adipose-derived stem cells, allowing long-term cryopreservation in DMSO-free and xeno-free conditions.

  19. Analysis of a Combined Antenna Arrays and Reverse-Link Synchronous DS-CDMA System over Multipath Rician Fading Channels

    OpenAIRE

    Kim Yong-Seok; Whang Keum-Chan

    2005-01-01

    We present the BER analysis of antenna array (AA) receiver in reverse-link asynchronous multipath Rician channels and analyze the performance of an improved AA system which applies a reverse-link synchronous transmission technique (RLSTT) in order to effectively make a better estimation of covariance matrices at a beamformer-RAKE receiver. In this work, we provide a comprehensive analysis of user capacity which reflects several important factors such as the ratio of the specular component pow...

  20. A case report of Schatzker type VI tibial plateau fracture treated with double reverse traction closed reduction combined with minimally invasive percutaneous plate osteosynthesis technique: A case report.

    Science.gov (United States)

    Li, Dian-Qing; Song, De-Ye; Ni, Jiang-Dong; Ding, Mu-Liang; Huang, Jun

    2017-11-01

    The knee joint is an important weight-bearing joint, tibial plateau fractures affect knee function and stability. High-energy intra-articular fractures involving the tibial plateau can cause management-related problems such as wound dehiscence; severe comminution leading to malalignment; and delayed complications such as varus collapse, implant failure, and arthritis of the knee joint. The treatment of severe or complex tibial plateau fractures can be quite difficult. Traditional methods of open reduction and plating require extensive exposures, which may further compromise soft tissue and devascularize bone fragments, leading to infection. In this case, a novel device, double reverse traction combined with MIPPO technique, was used and provided the possibility of minimally invasive and personalized orthopedic surgery to treat severe comminuted Schatzker type VI tibial plateau fracture and tibial shaft fracture and got satisfactory results. A previously healthy 56-year-old man presented to the emergency room after a fall from a height, who lost the movement of the left knee with pain and swelling. X-rays showed a tibial plateau comminuted fracture, Schatzker type VI, and tibial shaft fracture. Applying less extensile exposure and the indirect reduction technique of double reverse traction and closed reduction combined with minimally invasive percutaneous plate osteosynthesis (MIPPO) technique, we got satisfactory recovery of the severe comminuted Schatzker type VI tibial plateau fracture and tibial shaft fracture. This severe comminuted fracture and tibial shaft fracture were successfully reduced and got satisfactory recovery of knee joint function. Double reverse traction combined with MIPPO technique can reduce the risk of surgical complications, such as bleeding, oozing, and wound infection. It can be applied in patients with comorbidities such as cardiac disease, hypertension, and heart failure who may otherwise not be candidates for surgery. The cost burden is

  1. Therapeutic efficacy of valproic acid in a combined monocrotaline and chronic hypoxia rat model of severe pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Beidi Lan

    Full Text Available Pulmonary hypertension (PH is a serious disease with poor prognosis. Reports show that cells in remodeled pulmonary arteries of PH patients have similar characteristics to cancer cells, such as exuberant inflammation, increased proliferation, and decreased apoptosis. An ideal strategy for developing PH therapies is to directly target pulmonary vascular remodeling. High levels of histone deacetylase (HDAC expression and activity are found in certain cancers, and research has shown the potential of HDAC inhibitors in repressing tumor growth via anti-inflammatory and anti-proliferative effects. To date, little is known about the effectiveness of HDAC inhibitors against pulmonary vascular remodeling in severe PH.To investigate whether class I HDAC inhibitors suppress or reverse the development of severe PH in rats.Male Sprague-Dawley rats were injected with a single, subcutaneous dose of monocrotaline (60 mg/kg, and were exposed to chronic hypoxia to induce severe PH. Valproic acid, a class I HDAC inhibitor, was administered to rats daily via gastric gavage (300 mg/kg in a PH prevention study (during the first 3 weeks or a PH reversal study (from 3 to 5 weeks. At the end of experiment, hemodynamic indices were measured, ventricular hypertrophy indices were calculated and vascular remodeling phenotypes were analyzed.After 3 weeks exposure to a combined stimulation of monocrotaline and chronic hypoxia, rats exhibited a reduced body weight, elevated right ventricular systolic pressure, an increased Fulton index, right ventricle weight ratio, medial wall thickness and muscularized peripheral pulmonary arteries. These parameters for PH evaluation were exacerbated from 3 to 5 weeks. Daily administration of valproic acid therapy prevented and partially reversed the development of severe PH in rats, and decreased inflammation and proliferation in remodeled pulmonary arteries.These data show that class I HDAC inhibitors may be effective for treating severe

  2. Rapidly reversible albumin and beta 2-microglobulin hyperexcretion in recent severe essential hypertension

    DEFF Research Database (Denmark)

    Christensen, Cramer

    1983-01-01

    Seven young patients with newly diagnosed severe hypertension were studied for one week. The mean age was 34.9 years (range 28-44). The mean initial values +/- s.d. for systolic and diastolic pressures were 223 +/- 27 and 141 +/- 8 mmHg, respectively. Secondary hypertension was excluded by conven...

  3. Neural Correlates of Reversal Learning in Severe Mood Dysregulation and Pediatric Bipolar Disorder

    Science.gov (United States)

    Adleman, Nancy E.; Kayser, Reilly; Dickstein, Daniel; Blair, R. James R.; Pine, Daniel; Leibenluft, Ellen

    2011-01-01

    Objective: Outcome and family history data differentiate children with severe mood dysregulation (SMD), a syndrome characterized by chronic irritability, from children with "classic" episodic bipolar disorder (BD). Nevertheless, the presence of cognitive inflexibility in SMD and BD highlights the need to delineate neurophysiologic similarities and…

  4. Surgical Revascularization Reverses Cerebral Cortical Thinning in Patients With Severe Cerebrovascular Steno-Occlusive Disease

    NARCIS (Netherlands)

    Fierstra, Jorn; MacLean, David B.; Fisher, Joseph A.; Han, Jay S.; Mandell, Daniel M.; Conklin, John; Poublanc, Julien; Crawley, Adrian P.; Regli, Luca; Mikulis, David J.; Tymianski, Michael

    Background and Purpose-Chronic deficiencies in regional blood flow lead to cerebral cortical thinning without evidence of gross tissue loss at the same time as potentially negatively impacting on neurological and cognitive performance. This is most pronounced in patients with severe occlusive

  5. Effect of pancreatic kallikrein combined with magnesium sulfate therapy on disease severity of patients with severe preeclampsia

    Directory of Open Access Journals (Sweden)

    Yi Yang

    2016-10-01

    Full Text Available Objective: To study the clinical effect of pancreatic kallikrein combined with magnesium sulfate therapy on severe preeclampsia. Methods: A total of 47 patients with severe preeclampsia treated in our hospital from May 2013 to October 2015 were retrospectively analyzed, patients who received pancreatic kallikrein combined with magnesium sulfate therapy were selected as observation group, patients who received magnesium sulfate therapy were selected as control group, and then blood pressure level, renal function, uterine artery and umbilical artery blood flow state, and hypoxia indexes in serum and placenta were compared between two groups. Results: After treatment, systolic pressure and diastolic pressure levels as well as serum CysC level and 24 h urine protein level of observation group were significantly lower than those of control group, the uterine artery and umbilical artery S/ D and PI were significantly lower than those of control group, PIGF and NO levels in serum as well as Xiap and Survivin levels in placenta were significantly higher than those of control group, and sVEGFR1 level in serum as well as Caspase-3 and Caspase-7 levels in placenta was significantly lower than those of control group. Conclusions: Pancreatic kallikrein combined with magnesium sulfate therapy can alleviate the disease severity, lower blood pressure and vascular resistance, and improve renal function and the apoptosis caused by placental hypoxia in patients with severe preeclampsia.

  6. Early orthopedic correction of skeletal Class III malocclusion using combined reverse twin block and face mask therapy

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Chugh

    2015-01-01

    Full Text Available A 6-year 8-month-old girl presented with a moderate Class III malocclusion characterized by mid-face deficiency and an anterior cross bite. In the first phase, the patient was treated with combination of reverse twin block and facemask therapy. In phase two, fixed appliances were placed in the permanent dentition. The post treatment results were good and a favorable growth tendency could be observed. The correction of the Class III malocclusion occurred by a combination of skeletal and dental improvements. This report shows successful correction of skeletal Class III malocclusion in the early transitional dentition using combination therapy.

  7. Early orthopedic correction of skeletal Class III malocclusion using combined reverse twin block and face mask therapy.

    Science.gov (United States)

    Chugh, Vinay Kumar; Tandon, Pradeep; Prasad, Veerendra; Chugh, Ankita

    2015-01-01

    A 6-year 8-month-old girl presented with a moderate Class III malocclusion characterized by mid-face deficiency and an anterior cross bite. In the first phase, the patient was treated with combination of reverse twin block and facemask therapy. In phase two, fixed appliances were placed in the permanent dentition. The post treatment results were good and a favorable growth tendency could be observed. The correction of the Class III malocclusion occurred by a combination of skeletal and dental improvements. This report shows successful correction of skeletal Class III malocclusion in the early transitional dentition using combination therapy.

  8. Lesson of the month 1: Obesity hypoventilation (Pickwickian) syndrome: a reversible cause of severe pulmonary hypertension.

    Science.gov (United States)

    Warricker, Frazer; Islam, Zafir; Shah, Benoy N

    2017-12-01

    Obesity hypoventilation syndrome (OHS) is a condition in which an individual with a body mass index >30 kg/m2 develops daytime alveolar hypoventilation (defined as a resting PaCO2 >45 mmHg) that cannot be attributed to other pathologies. It is a condition with increasing prevalence and rising cost to healthcare systems worldwide. Right heart failure and pulmonary hypertension are well-known complications of this syndrome. Here, we present the case of a female patient with OHS who presented to our centre with severe pulmonary hypertension, which resolved with appropriate treatment. We also review this clinical condition and its diagnosis and management. © Royal College of Physicians 2017. All rights reserved.

  9. Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients

    Directory of Open Access Journals (Sweden)

    Morana Jaganjac

    2017-08-01

    Conclusion: This study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are needed to evaluate involvement of 4-HNE in metabolically impaired abdominal adipogenesis and to confirm benefits of combined metformin-insulin therapy in T2DM patients.

  10. Long-term follow-up of severely symptomatic women with adenomyoma treated with combination therapy

    Directory of Open Access Journals (Sweden)

    Wei-Min Liu

    2013-03-01

    Conclusion: Combination therapy for adenomyoma provides an effective treatment option for long-term symptom control and uterine preservation in severely symptomatic women for whom previous long-term drug therapy has failed or proven to be intolerable.

  11. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening

    NARCIS (Netherlands)

    A.P.J. de Pagter (Anne); R.G.M. Bredius (Robbert); T.W. Kuijpers (Taco W.); J. Tramper (Jelco); M. van der Burg (Mirjam); J.M. van Montfrans (Joris); G.J.A. Driessen (Gertjan)

    2015-01-01

    textabstractSevere combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment

  12. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening.

    NARCIS (Netherlands)

    Pagter, A.P. de; Bredius, R.G.; Kuijpers, T.W.; Tramper, J.; Burg, M. van der; Montfrans, J. van; Driessen, G.J.; Flier, M. van der

    2015-01-01

    Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The

  13. Overview of 15-year severe combined immunodeficiency in the Netherlands : towards newborn blood spot screening

    NARCIS (Netherlands)

    de Pagter, Anne P. J.; Bredius, Robbert G. M.; Kuijpers, Taco W.; Tramper, Jelco; van der Burg, Mirjam; van Montfrans, JM; Driessen, Gertjan J.

    Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The

  14. TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease : A Systematic Review

    NARCIS (Netherlands)

    van der Spek, Jet; Groenwold, Rolf H. H.; van der Burg, Mirjam; van Montfrans, JM

    Background Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) in neonatal dried blood spots (DBS) enables early diagnosis of severe combined immunodeficiency disease (SCID). In recent years, different screening algorithms for TREC based SCID screening were reported.

  15. Newborn Screening for Primary Immunodeficiencies: Focus on Severe Combined Immunodeficiency (SCID and Other Severe T-Cell Lymphopenias

    Directory of Open Access Journals (Sweden)

    Stephan Borte

    2015-12-01

    Full Text Available Primary immunodeficiencies (PID are congenital disorders of immune competence, which are mainly characterized by a pathological susceptibility to infection. More than 240 PID disease entities have been defined so far, accounting for a broad spectrum of clinical symptoms and severity. Severe PID are increasingly becoming appreciated as a relevant health problem, and diagnostic procedures and screening profiles to allow earliest possible diagnosis on a population scale have already been developed in the USA and few European countries. The most severe PID are characterized by significant mortality in the first years of life, as well as serious morbidity with irreversible organ damage. This applies in particular to PID that are defined by the absence or functional anergy of T-lymphocytes (severe combined immunodeficiency; SCID or B-lymphocytes (e.g., X-linked agammaglobulinemia; XLA. A strategy to improve the outcome of severe PID by prompt diagnosis and immediate adequate treatment is screening newborns for the presence of T and B cells.

  16. Reverse-flow anterolateral thigh perforator: an ad hoc flap for severe post-burn knee contracture.

    Science.gov (United States)

    Ismail, H A; El-Bassiony, L E

    2016-03-31

    We evaluate function outcomes of the reverse-flow ALT perforator flap to reconstruct severe post-burn knee contracture. Between October 2012 and December 2014, 10 patients with severe post-burn knee contracture were subjected to reconstruction with 10 ipsilateral reversed-flow ALT perforator flaps. All the patients were male. Ages ranged from 15 to 47 years (mean = 32 years). Time from burn injury to patient presentation ranged from 2-8 months. All patients demonstrated post-burn flexion contracture of the knee joint, ranging from 35 to 75 degrees. Flap sizes ranged from 8×16 to 12×26 cm. The flaps and skin grafts were carried out without major complications. Only minor complications occurred, such as transient, mild congestion immediately after inset in two flaps. Two flaps developed superficial necrosis at the distal edge. One case sustained partial skin graft loss due to haematoma. One case complained of skin hyperpigmentation and hypertrophic scars around the graft. Secondary debulking procedures were required in two cases. The entire donor sites were closed by partial thickness skin graft with acceptable appearance, except one case that was closed primarily. Eight out of ten patients (80%) demonstrated gradual improvement in range of knee motion after a specialized rehabilitation program. Two patients (20%) did not get back full range of motion. RALT perforator flap is the cornerstone for the reconstruction of soft-tissue defects around the knee with acceptable aesthetic and functional results provided that the following items are fulfilled: inclusion of muscle cuff around the pedicle, the pivot point, prevention of pedicle compression after transfer and early surgical intervention on the post-burn knee contracture.

  17. Protein Footprinting by the Combined Use of Reversible and Irreversible Lysine Modifications

    Science.gov (United States)

    Hanai, Ryo; Wang, James C.

    1994-12-01

    A two-step lysine-modification procedure has been devised to chemically footprint protein surfaces involved in macromolecular interactions. A protein tagged at one particular end, in the free state or in a complex, is first treated lightly with a reversible lysine-modifying reagent. The protein is then unfolded and treated extensively with an irreversible lysine reagent to block those lysines that did not react previously; next, the first lysine modification is reversed, and a lysine-specific endoproteinase is used to cleave the tagged polypeptide at the deblocked lysines. Separation of the proteolytic products by size and identification of the tagged fragments map the positions of these lysines. In this procedure, the reversible lysine reagent serves as the chemical footprinting agent, as cleavage of the polypeptide ensues only at the sites of reaction with this reagent. Lysines involved in macromolecular contacts are identified from differences in proteolytic patterns of the tagged protein when the first lysine modification is done with the protein in the free form and in a complex. Application of the method to vaccinia virus topoisomerase identifies a number of lysines that are involved in its binding to DNA.

  18. Subacute combined spinal cord degeneration and pancytopenia secondary to severe vitamin B12 deficiency

    Directory of Open Access Journals (Sweden)

    José Luis Cabrerizo-García

    Full Text Available CONTEXT: Decreased vitamin B12 concentration does not usually result in clinical or hematological abnormalities. Subacute combined spinal cord degeneration and pancytopenia are two serious and rarely displayed consequences that appear in severe deficits. CASE REPORT: We present the case of a patient with subacute combined spinal cord degeneration and pancytopenia secondary to severe and sustained vitamin B12 deficiency. Such cases are rare nowadays and have potentially fatal consequences. CONCLUSIONS: Vitamin B12 deficiency should be taken into consideration in the differential diagnosis in cases of blood disorders or severe neurological symptoms. Early diagnosis and treatment can avoid irreversible consequences.

  19. Combination of expansion and orthognathic surgery in a severe hyperdivergent skeletal Class III malocclusion

    Directory of Open Access Journals (Sweden)

    Anadha Gujar

    2016-01-01

    Full Text Available Class III malocclusions with a severe hyperdivergent growth pattern are very complex to plan and treat. This case report describes the treatment of an adult with a skeletal Class III malocclusion with a midface deficiency, severe bilateral posterior crossbite, and a severe hyperdivergent growth pattern by a combination of a bonded rapid maxillary expansion appliance and surgical procedure of Le Fort I osteotomy for maxillary advancement.

  20. Combination Treatment With Anti-CD20 and Oral Anti-CD3 Prevents and Reverses Autoimmune Diabetes

    Science.gov (United States)

    Hu, Changyun; Ding, Heyuan; Zhang, Xiaojun; Wong, F. Susan; Wen, Li

    2013-01-01

    Type 1 diabetes (T1D) is a T cell–mediated autoimmune disease, although B cells also play an important role in T1D development. Both T cell– and B cell–directed immunotherapies have shown efficacy in the prevention and reversal of T1D. However, whether the combined strategy of targeting both T and B cells could further improve therapeutic efficacy remains to be explored. We show that combined treatment with intravenous antihuman CD20 (hCD20) and oral anti-CD3 significantly delays diabetes development in prediabetic hCD20 transgenic NOD mice. More importantly, the combined treatment reverses diabetes in >60% of mice newly diagnosed with diabetes. Further mechanistic studies demonstrated that the addition of oral anti-CD3 to the B-cell depletion therapy synergistically enhances the suppressive function of regulatory T cells. Of note, the oral anti-CD3 treatment induced a fraction of interleukin (IL)-10–producing CD4 T cells in the small intestine through IL-10– and IL-27–producing dendritic cells. Thus, the findings demonstrate that combining anti-CD20 and oral anti-CD3 is superior to anti-CD20 monotherapy for restoring normoglycemia in diabetic NOD mice, providing important preclinical evidence for the optimization of B cell–directed therapy for T1D. PMID:23447122

  1. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells.

    Science.gov (United States)

    Kuijpers, Taco W; van Leeuwen, Ester M M; Barendregt, Barbara H; Klarenbeek, Paul; aan de Kerk, Daan J; Baars, Paul A; Jansen, Machiel H; de Vries, Niek; van Lier, René A W; van der Burg, Mirjam

    2013-07-01

    Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8(+) T cells and increased over time. Only the revertant CD8(+) T cells showed normal expression of CD132 and the various CD8(+) T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ(+) T cells and differentiated CD4(+)CD27(-) effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8(+) T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells.

  2. Analysis of a Combined Antenna Arrays and Reverse-Link Synchronous DS-CDMA System over Multipath Rician Fading Channels

    Directory of Open Access Journals (Sweden)

    Kim Yong-Seok

    2005-01-01

    Full Text Available We present the BER analysis of antenna array (AA receiver in reverse-link asynchronous multipath Rician channels and analyze the performance of an improved AA system which applies a reverse-link synchronous transmission technique (RLSTT in order to effectively make a better estimation of covariance matrices at a beamformer-RAKE receiver. In this work, we provide a comprehensive analysis of user capacity which reflects several important factors such as the ratio of the specular component power to the Rayleigh fading power, the shape of multipath intensity profile, and the number of antennas. Theoretical analysis demonstrates that for the case of a strong specular path's power or for a high decay factor, the employment of RLSTT along with AA has the potential of improving the achievable capacity by an order of magnitude.

  3. Impact of combined clenbuterol and metoprolol therapy on reverse remodelling during mechanical unloading.

    Directory of Open Access Journals (Sweden)

    Manoraj Navaratnarajah

    Full Text Available Clenbuterol (Cl, a β2 agonist, is associated with enhanced myocardial recovery during left ventricular assist device (LVAD support, and exerts beneficial remodelling effects during mechanical unloading (MU in rodent heart failure (HF. However, the specific effects of combined Cl+β1 blockade during MU are unknown.We studied the chronic effects (4 weeks of β2-adrenoceptor (AR stimulation via Cl (2 mg/kg/day alone, and in combination with β1-AR blockade using metoprolol ((Met, 250 mg/kg/day, on whole heart/cell structure, function and excitation-contraction (EC coupling in failing (induced by left coronary artery (LCA ligation, and unloaded (induced by heterotopic abdominal heart transplantation (HATx failing rat hearts. Combined Cl+Met therapy displayed favourable effects in HF: Met enhanced Cl's improvement in ejection fraction (EF whilst preventing Cl-induced hypertrophy and tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MU-induced myocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+ transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Met mono-therapy, but these benefits, together with Cl's enhancement of sarcomeric contraction speed, and MU-induced recovery of Ca2+ spark frequency, disappeared during combined therapy.Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appears inferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined β2-AR simulation +β1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective as mono-therapy in enhancing myocardial recovery during LVAD support.

  4. Combined laparoscopic cholecystectomy with ileostomy reversal: A method of delayed definitive management of postoperative gallstone pancreatitis

    Directory of Open Access Journals (Sweden)

    Gaurav V Kulkarni

    2014-01-01

    Full Text Available Traditional management of gallstone pancreatitis (GP has been to perform cholecystectomy during the same hospital admission after resolution. However, when GP develops in the immediate postoperative period from a major colorectal operation, cholecystectomy may be fraught with difficulty due to the inflammatory response that occurs. Thus, delaying cholecystectomy until the inflammatory response subsides may be worthwhile, and it maximizes the chances of completing the cholecystectomy laparoscopically. We have described our management of 2 patients with GP occurring after colorectal operations, which required proximal diverting ileostomy. In both cases, we deferred management of GP with either endoscopic retrograde cholangiopancreatography (ERCP or medical conservative measures during the acute attack and performed laparoscopic cholecystectomy during ostomy reversal surgery utilizing the existing ostomy takedown site for port placement. Both patients tolerated this management well.

  5. Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease

    Directory of Open Access Journals (Sweden)

    Hema Mittal

    2014-01-01

    Full Text Available Fatal-disseminated Bacillus Calmette Guerin (BCG disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature.

  6. Chronic administration of gabapentin and a gabapentin-carbamazepine combination reversibly suppress testicular function in male Wistar rats (Rattus norvegicus).

    Science.gov (United States)

    Osuntokun, Opeyemi Samson; Olayiwola, Gbola; Oladele, Ayowole; Ola, Idowu; AyokaAbiodun, Oludele

    2017-06-01

    The effect of chronic administration of gabapentin, carbamazepine or a gabapentin-carbamazepine combination on testicular function in male rats was investigated to determine the effect of combining reduced doses of anti-epileptic drugs on the management of seizures, particularly with respect to the testis sequellae of chronic anti-epileptic administration. Male rats were randomized into four groups (n=10). Each group received daily intraperitoneal (i.p.) injections for 28days as follows: Group I, normal saline 0.1mL/day; Group II, gabapentin (GBP) 16mg/kg/day; Group III, carbamazepine (CBZ) 20mg/kg/day; and Group IV, sub-therapeutic doses of both GBP (8mg/kg) and CBZ (10mg/kg)/day. Twenty-four hours after the last treatment, five rats from each group were sacrificed and the remaining rats were allowed to recover for another four weeks. Sperm characteristics, serum testosterone, and histological integrity of the testis was assessed 24h after treatment and after 28days of drug withdrawal. GBP, CBZ, and GBP-CBZ combination significantly reduced the absolute weight of the testis, epididymis, and seminal vesicle (p<0.05). Moreover, epididymal sperm count and morphology were significantly decreased (p<0.05) in GBP, CBZ, and GBP-CBZ groups. Reduction in serum levels of testosterone for all of the treated groups was statistically significant (p<0.05). The cytoarchitecture of the testicular tissue in the testis of CBZ and GBP-CBZ groups showed disorganization. The altered testicular function were almost restored in GBP treated rats. CBZ and GBP-CBZ combination have delayed but reversible antifertility in the rats. Hence, chronic administration of GBP, CBZ, and GBP-CBZ combination reversibly reduced testicular function in male rats. Copyright © 2017. Published by Elsevier B.V.

  7. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Sílvia Bacalhau

    2011-01-01

    Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.

  8. Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole.

    Science.gov (United States)

    Li, Xiuyun; Zhao, Yuanhao; Huang, Xin; Yu, Cuixiang; Yang, Yilei; Sun, Shujuan

    2017-01-01

    In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic Candida albicans (C. albicans) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans. With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans, increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans. The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.

  9. TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review

    NARCIS (Netherlands)

    J. van der Spek (Jet); R.H.H. Groenwold (Rolf H. H.); M. van der Burg (Mirjam); J.M. van Montfrans (Joris)

    2015-01-01

    textabstractBackground: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) in neonatal dried blood spots (DBS) enables early diagnosis of severe combined immunodeficiency disease (SCID). In recent years, different screening algorithms for TREC based SCID screening were

  10. Economic Evaluation of a Hybrid Desalination System Combining Forward and Reverse Osmosis

    Science.gov (United States)

    Choi, Yongjun; Cho, Hyeongrak; Shin, Yonghyun; Jang, Yongsun; Lee, Sangho

    2015-01-01

    This study seeks to evaluate the performance and economic feasibility of the forward osmosis (FO)–reverse osmosis (RO) hybrid process; to propose a guideline by which this hybrid process might be more price-competitive in the field. A solution-diffusion model modified with film theory was applied to analyze the effects of concentration polarization, water, and salt transport coefficient on flux, recovery, seawater concentration, and treated wastewater of the FO process of an FO-RO hybrid system. A simple cost model was applied to analyze the effects of flux; recovery of the FO process; energy; and membrane cost on the FO-RO hybrid process. The simulation results showed that the water transport coefficient and internal concentration polarization resistance are very important factors that affect performance in the FO process; however; the effect of the salt transport coefficient does not seem to be large. It was also found that the flux and recovery of the FO process, the FO membrane, and the electricity cost are very important factors that influence the water cost of an FO-RO hybrid system. This hybrid system can be price-competitive with RO systems when its recovery rate is very high, the flux and the membrane cost of the FO are similar to those of the RO, and the electricity cost is expensive. The most important thing in commercializing the FO process is enhancing performance (e.g.; flux and the recovery of FO membranes). PMID:26729176

  11. Economic Evaluation of a Hybrid Desalination System Combining Forward and Reverse Osmosis

    Directory of Open Access Journals (Sweden)

    Yongjun Choi

    2015-12-01

    Full Text Available This study seeks to evaluate the performance and economic feasibility of the forward osmosis (FO–reverse osmosis (RO hybrid process; to propose a guideline by which this hybrid process might be more price-competitive in the field. A solution-diffusion model modified with film theory was applied to analyze the effects of concentration polarization, water, and salt transport coefficient on flux, recovery, seawater concentration, and treated wastewater of the FO process of an FO-RO hybrid system. A simple cost model was applied to analyze the effects of flux; recovery of the FO process; energy; and membrane cost on the FO-RO hybrid process. The simulation results showed that the water transport coefficient and internal concentration polarization resistance are very important factors that affect performance in the FO process; however; the effect of the salt transport coefficient does not seem to be large. It was also found that the flux and recovery of the FO process, the FO membrane, and the electricity cost are very important factors that influence the water cost of an FO-RO hybrid system. This hybrid system can be price-competitive with RO systems when its recovery rate is very high, the flux and the membrane cost of the FO are similar to those of the RO, and the electricity cost is expensive. The most important thing in commercializing the FO process is enhancing performance (e.g.; flux and the recovery of FO membranes.

  12. Economic Evaluation of a Hybrid Desalination System Combining Forward and Reverse Osmosis.

    Science.gov (United States)

    Choi, Yongjun; Cho, Hyeongrak; Shin, Yonghyun; Jang, Yongsun; Lee, Sangho

    2015-12-29

    This study seeks to evaluate the performance and economic feasibility of the forward osmosis (FO)-reverse osmosis (RO) hybrid process; to propose a guideline by which this hybrid process might be more price-competitive in the field. A solution-diffusion model modified with film theory was applied to analyze the effects of concentration polarization, water, and salt transport coefficient on flux, recovery, seawater concentration, and treated wastewater of the FO process of an FO-RO hybrid system. A simple cost model was applied to analyze the effects of flux; recovery of the FO process; energy; and membrane cost on the FO-RO hybrid process. The simulation results showed that the water transport coefficient and internal concentration polarization resistance are very important factors that affect performance in the FO process; however; the effect of the salt transport coefficient does not seem to be large. It was also found that the flux and recovery of the FO process, the FO membrane, and the electricity cost are very important factors that influence the water cost of an FO-RO hybrid system. This hybrid system can be price-competitive with RO systems when its recovery rate is very high, the flux and the membrane cost of the FO are similar to those of the RO, and the electricity cost is expensive. The most important thing in commercializing the FO process is enhancing performance (e.g.; flux and the recovery of FO membranes).

  13. Correction: Large-scale electricity storage utilizing reversible solid oxide cells combined with underground storage of CO2 and CH4

    DEFF Research Database (Denmark)

    Jensen, Søren Højgaard; Graves, Christopher R.; Mogensen, Mogens Bjerg

    2017-01-01

    Correction for ‘Large-scale electricity storage utilizing reversible solid oxide cells combined with underground storage of CO2 and CH4’ by S. H. Jensen et al., Energy Environ. Sci., 2015, 8, 2471–2479.......Correction for ‘Large-scale electricity storage utilizing reversible solid oxide cells combined with underground storage of CO2 and CH4’ by S. H. Jensen et al., Energy Environ. Sci., 2015, 8, 2471–2479....

  14. Aphasia severity in chronic stroke patients: a combined disconnection in the dorsal and ventral language pathways.

    Science.gov (United States)

    Rosso, Charlotte; Vargas, Patricia; Valabregue, Romain; Arbizu, Céline; Henry-Amar, François; Leger, Anne; Lehéricy, Stéphane; Samson, Yves

    2015-01-01

    The contribution of lesion size and location in poststroke aphasia is debated, especially the extent to which aphasia severity is affected by damage to specific white matter areas. To identify specific white matter areas critical for poststroke aphasia global severity and to determine whether injury to these areas had more impact on aphasia severity than the infarct volume. Twenty-three chronic poststroke aphasic patients were assessed with the Aphasia Rapid Test (ART) and the Boston Diagnosis Aphasia Examination (BDAE) global severity scales and underwent diffusion tensor and structural imaging. Voxel-based diffusion tensor imaging regression analysis was used to determine in which areas fractional anisotropy (FA) abnormalities were correlated with ART and BDAE severity scales. The relationships between aphasia severity, FA values, and infarct volumes were investigated using global and partial correlations. We found a critical area associated with aphasia severity overlapping with the arcuate and the inferior fronto-occipital fasciculi, resulting in a combined disconnection of the dorsal and ventral pathways. ART scores were inversely correlated with FA values in this region, with greater severity present with lower FA values (correlation coefficient = -0.833, P aphasia severity disappeared when damage to this critical white matter area was taken into account (P = .38). The assessment of the integrity of this region may potentially have a clinical impact in neurorehabilitation and acute decision making. © The Author(s) 2014.

  15. Combined osteotomy in patients with severe Legg-Calve-Perthes disease.

    Science.gov (United States)

    Eamsobhana, Perajit; Kaewpornsawan, Kamolporn

    2012-10-01

    The purpose of the present study was to describe the clinical and radiographic results obtained with the combined osteotomy in patients with severe Legg-Calve-Perthes disease. During 2000 to 2010 patients with Legg-Calve-Perthes disease who intervened with combined osteotomy at Siriraj Hospital were evaluated. Clinical evaluation was categorized by Ratliff classification and radiographic evaluation was performed by Moss index, Lloyd Roberts classification and Stulberg classification. Twenty patients intervened with combined osteotomy. There were nineteen males and one female with a mean age of 7.7 years. The average follow-up was 49 months. Nine had a Catterall III and eleven had a Catterall IV. According to Herring classification, fourteen patients were Herring B and six were Herring C. In accordance with the Ratliff classification, the postoperative clinical results: fifteen good, three fair and two poor. According to Mose scale, eight patients had good results, nine had fair results and three had poor results. According to the Lloyd-Roberts classification eight patients had good results, nine had fair results and three had poor results. Based on the Stulberg classification, there were ten patients in class II, nine in class III and one in class V. The surgical treatment for severe Perthes disease with the best expected outcome is still a challenge. According to the results reported here, the combined osteotomy is safe and effective procedure for patients with severe Perthes disease in whom the femoral head cannot be contained by conventional forms of treatment.

  16. Cocaine use severity and cerebellar gray matter are associated with reversal learning deficits in cocaine-dependent individuals

    NARCIS (Netherlands)

    Moreno-López, L.; Perales, J.C.; van Son, D.; Albein-Urios, N.; Soriano-Mas, C.; Martinez-Gonzalez, J.M.; Wiers, R.W.; Verdejo-García, A.

    2015-01-01

    Cocaine addiction involves persistent deficits to unlearn previously rewarded response options, potentially due to neuroadaptations in learning-sensitive regions. Cocaine-targeted prefrontal systems have been consistently associated with reinforcement learning and reversal deficits, but more recent

  17. Fumaric acid esters in severe psoriasis, including experience of use in combination with other systemic modalities.

    Science.gov (United States)

    Balasubramaniam, P; Stevenson, O; Berth-Jones, J

    2004-04-01

    Fumaric acid esters (FAE) are used as a systemic treatment for severe psoriasis in Germany but there has been only very little published experience from the U.K. The potential for use in combination with other systemic drugs has not been explored. To present data relating to the efficacy of FAE in severe psoriasis and to examine the potential dose-sparing effect and safety issues when FAE are combined with other systemic agents. We retrospectively analysed the records of patients who had received FAE for severe psoriasis either alone (in two cases) or along with other systemic medications (in 10 cases). We reviewed the efficacy of FAE and assessed whether dose reductions were achieved for other systemic drugs. Patients were monitored carefully for possible adverse effects. Of 12 patients treated with FAE one discontinued the drug very early, due to flushing, while on a very low dose. The other 11 patients all demonstrated an improvement in psoriasis after starting FAE. Nine patients received FAE in combination with other systemic therapies including ciclosporin, acitretin, hydroxyurea and methotrexate. Seven achieved useful overall reductions in the dose of the other drugs. In two patients severe psoriasis was controlled using FAE alone. The side-effect profile of FAE was similar to that previously reported. There was no evidence of drug interactions. FAE appear effective and less toxic than other systemic treatments for psoriasis. FAE were used successfully in combination with other systemic agents and generally enabled the doses of the more hazardous drugs to be reduced. Extremely careful monitoring is required when using FAE in such combined regimens as experience is currently very limited.

  18. A study on quantifying COPD severity by combining pulmonary function tests and CT image analysis

    Science.gov (United States)

    Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

    2011-03-01

    This paper describes a novel method that can evaluate chronic obstructive pulmonary disease (COPD) severity by combining measurements of pulmonary function tests and measurements obtained from CT image analysis. There is no cure for COPD. However, with regular medical care and consistent patient compliance with treatments and lifestyle changes, the symptoms of COPD can be minimized and progression of the disease can be slowed. Therefore, many diagnosis methods based on CT image analysis have been proposed for quantifying COPD. Most of diagnosis methods for COPD extract the lesions as low-attenuation areas (LAA) by thresholding and evaluate the COPD severity by calculating the LAA in the lung (LAA%). However, COPD is usually the result of a combination of two conditions, emphysema and chronic obstructive bronchitis. Therefore, the previous methods based on only LAA% do not work well. The proposed method utilizes both of information including the measurements of pulmonary function tests and the results of the chest CT image analysis to evaluate the COPD severity. In this paper, we utilize a multi-class AdaBoost to combine both of information and classify the COPD severity into five stages automatically. The experimental results revealed that the accuracy rate of the proposed method was 88.9% (resubstitution scheme) and 64.4% (leave-one-out scheme).

  19. Chimerism in a child with severe combined immunodeficiency: a case report.

    Science.gov (United States)

    Aureli, Anna; Piancatelli, Daniela; Monaco, Palmina I; Ozzella, Giuseppina; Canossi, Angelica; Piazza, Antonina; Isacchi, Giancarlo; Caniglia, Maurizio; Adorno, Domenico

    2006-09-01

    Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders in which there is a combined absence of T-lymphocyte and B-lymphocyte function. Children with SCID die within two years of age, if untreated. The effective treatment for SCID is a hematopoietic stem cell transplantation (HSCT). It has been repeatedly described that in peripheral blood of infants with SCID maternal T cells can be found. Here we report a case of blood chimerism in a one-year-old boy with SCID.

  20. Combined Inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas.

    Directory of Open Access Journals (Sweden)

    Phuoc T Tran

    2008-05-01

    Full Text Available Conditional transgenic models have established that tumors require sustained oncogene activation for tumor maintenance, exhibiting the phenomenon known as "oncogene-addiction." However, most cancers are caused by multiple genetic events making it difficult to determine which oncogenes or combination of oncogenes will be the most effective targets for their treatment.To examine how the MYC and K-ras(G12D oncogenes cooperate for the initiation and maintenance of tumorigenesis, we generated double conditional transgenic tumor models of lung adenocarcinoma and lymphoma. The ability of MYC and K-ras(G12D to cooperate for tumorigenesis and the ability of the inactivation of these oncogenes to result in tumor regression depended upon the specific tissue context. MYC-, K-ras(G12D- or MYC/K-ras(G12D-induced lymphomas exhibited sustained regression upon the inactivation of either or both oncogenes. However, in marked contrast, MYC-induced lung tumors failed to regress completely upon oncogene inactivation; whereas K-ras(G12D-induced lung tumors regressed completely. Importantly, the combined inactivation of both MYC and K-ras(G12D resulted more frequently in complete lung tumor regression. To account for the different roles of MYC and K-ras(G12D in maintenance of lung tumors, we found that the down-stream mediators of K-ras(G12D signaling, Stat3 and Stat5, are dephosphorylated following conditional K-ras(G12D but not MYC inactivation. In contrast, Stat3 becomes dephosphorylated in lymphoma cells upon inactivation of MYC and/or K-ras(G12D. Interestingly, MYC-induced lung tumors that failed to regress upon MYC inactivation were found to have persistent Stat3 and Stat5 phosphorylation.Taken together, our findings point to the importance of the K-Ras and associated down-stream Stat effector pathways in the initiation and maintenance of lymphomas and lung tumors. We suggest that combined targeting of oncogenic pathways is more likely to be effective in the

  1. Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency.

    Science.gov (United States)

    Szczawinska-Poplonyk, Aleksandra; Jonczyk-Potoczna, Katarzyna; Breborowicz, Anna; Bartkowska-Sniatkowska, Alicja; Figlerowicz, Magdalena

    2013-09-01

    Coronaviruses have been demonstrated to contribute substantially to respiratory tract infections among the child population. Though infected children commonly present mild upper airway symptoms, in high-risk patients with underlying conditions, particularly in immunocompromised children these pathogens may lead to severe lung infection and extrapulmonary disorders. In this paper, we provide the first report of the case of a 15-month-old child with severe combined immunodeficiency and coronavirus HKU1-related pneumonia with fatal respiratory distress syndrome. © 2012 John Wiley & Sons Ltd.

  2. Combined Reversed Phase HPLC, Mass Spectrometry, and NMR Spectroscopy for a Fast Separation and Efficient Identification of Phosphatidylcholines

    Science.gov (United States)

    Willmann, Jan; Thiele, Herbert; Leibfritz, Dieter

    2011-01-01

    In respect of the manifold involvement of lipids in biochemical processes, the analysis of intact and underivatised lipids of body fluids as well as cell and tissue extracts is still a challenging task, if detailed molecular information is required. Therefore, the advantage of combined use of high-pressure liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy will be shown analyzing three different types of extracts of the ubiquitous membrane component phosphatidylcholine. At first, different reversed phase modifications were tested on phosphatidylcholines (PC) with the same effective carbon number (ECN) for their applicability in lipid analysis. The results were taken to improve the separation of three natural PC extract types and a new reversed phase (RP)-HPLC method was developed. The individual species were characterized by one- and two-dimensional NMR and positive or negative ion mode quadrupole time of flight (q-TOF)-MS as well as MS/MS techniques. Furthermore, ion suppression effects during electrospray ionisation (ESI), difficulties, limits, and advantages of the individual analytical techniques are addressed. PMID:20871812

  3. Study of the validity of a combined potential model using the Hybrid Reverse Monte Carlo method in Fluoride glass system

    Directory of Open Access Journals (Sweden)

    M. Kotbi

    2013-03-01

    Full Text Available The choice of appropriate interaction models is among the major disadvantages of conventional methods such as Molecular Dynamics (MD and Monte Carlo (MC simulations. On the other hand, the so-called Reverse Monte Carlo (RMC method, based on experimental data, can be applied without any interatomic and/or intermolecular interactions. The RMC results are accompanied by artificial satellite peaks. To remedy this problem, we use an extension of the RMC algorithm, which introduces an energy penalty term into the acceptance criteria. This method is referred to as the Hybrid Reverse Monte Carlo (HRMC method. The idea of this paper is to test the validity of a combined potential model of coulomb and Lennard-Jones in a Fluoride glass system BaMnMF7 (M = Fe,V using HRMC method. The results show a good agreement between experimental and calculated characteristics, as well as a meaningful improvement in partial pair distribution functions (PDFs. We suggest that this model should be used in calculating the structural properties and in describing the average correlations between components of fluoride glass or a similar system. We also suggest that HRMC could be useful as a tool for testing the interaction potential models, as well as for conventional applications.

  4. Combined Reversed Phase HPLC, Mass Spectrometry, and NMR Spectroscopy for a Fast Separation and Efficient Identification of Phosphatidylcholines

    Directory of Open Access Journals (Sweden)

    Jan Willmann

    2011-01-01

    Full Text Available In respect of the manifold involvement of lipids in biochemical processes, the analysis of intact and underivatised lipids of body fluids as well as cell and tissue extracts is still a challenging task, if detailed molecular information is required. Therefore, the advantage of combined use of high-pressure liquid chromatography (HPLC, mass spectrometry (MS, and nuclear magnetic resonance (NMR spectroscopy will be shown analyzing three different types of extracts of the ubiquitous membrane component phosphatidylcholine. At first, different reversed phase modifications were tested on phosphatidylcholines (PC with the same effective carbon number (ECN for their applicability in lipid analysis. The results were taken to improve the separation of three natural PC extract types and a new reversed phase (RP-HPLC method was developed. The individual species were characterized by one- and two-dimensional NMR and positive or negative ion mode quadrupole time of flight (q-TOF-MS as well as MS/MS techniques. Furthermore, ion suppression effects during electrospray ionisation (ESI, difficulties, limits, and advantages of the individual analytical techniques are addressed.

  5. Severe hyperpigmentation and scarring following glycolic acid peel treatment in combination with low-dose isotretinoin.

    Science.gov (United States)

    Gerber, Peter Arne; Kukova, Gabriela; Bölke, Edwin; Homey, Bernhard; Diedrichson, Evelyn

    2014-11-07

    The application of systemic isotretinoin in the treatment of cutaneous photoaging has been well investigated. In addition, well-recognized topical antiaging therapies such as superficial chemical peeling (CP) with α-hydroxy acids have been shown to be more helpful when combined with low-dose oral isotretinoin. Even though the combination of systemic isotretinoin and medium to deep CP has been associated with serious side effects such as delayed wound healing and enlarged incidence of scarring, to date superficial CP and concomitant systemic isotretinoin have been considered safe. In this report, we present the case of a patient receiving low-dose oral isotretinoin therapy who developed severe painful erythema and erosions that led to permanent hyperpigmentation and scarring of her face and neck after undergoing superficial CP with glycolic acid. There is a potential risk of hyperpigmentation and scarring with the use of a combination of low-dose oral isotretinoin and glycolic acid peeling.

  6. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts.

    Science.gov (United States)

    Vafaei, Ali; Ranjkesh, Bahram; Lovschall, Henrik; Erfanparast, Leila; Jafarabadi, Mohammad A; Oskouei, Sina Ghertasi; Isidor, Flemming

    2016-01-01

    The aim of this study was to compare the survival of composite resin restorations retained by glass fiber posts or reversed-orientated (upside-down) metal posts in severely decayed primary anterior teeth after 6, 12, and 18 months. A total of forty-four 3- to 5-year-old children with bilateral severely decayed primary maxillary canines were included. Patients were treated under general anesthesia. After pulpectomy, an intracanal post was seated in the primary maxillary canine on each side: either a glass fiber post or a metallic post in reversed orientation and teeth restored with light-cured composite. Survival rate of each technique was evaluated at predetermined follow-ups and data were analyzed with McNemar's test (α = 0.05). The difference in survival of restorations retained by two types of posts was not statistically significant in clinical and radiographical evaluations after 6, 12, and 18 months. The survival rate of reversed-orientated metal and glass fiber posts after 18 months was 81.1 and 67.6% respectively (p = 0.14). Reversed-orientated metal post did not show lower clinical survival compared with glass fiber posts in 18-month follow-up. Hence, reversed-orientated metal post can be considered as a potential method to obtain retention for composite restorations in severely decayed primary anterior teeth. How to cite this article: Vafaei A, Ranjkesh B, L0vschall H, Erfanparast L, Jafarabadi MA, Oskouei SG, Isidor F. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts. Int J Clin Pediatr Dent 2016;9(2):109-113.

  7. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts

    Science.gov (United States)

    Ranjkesh, Bahram; Lovschall, Henrik; Erfanparast, Leila; Jafarabadi, Mohammad A; Oskouei, Sina Ghertasi; Isidor, Flemming

    2016-01-01

    ABSTRACT Aim: The aim of this study was to compare the survival of composite resin restorations retained by glass fiber posts or reversed-orientated (upside-down) metal posts in severely decayed primary anterior teeth after 6, 12, and 18 months. Materials and methods: A total of forty-four 3- to 5-year-old children with bilateral severely decayed primary maxillary canines were included. Patients were treated under general anesthesia. After pulpectomy, an intracanal post was seated in the primary maxillary canine on each side: either a glass fiber post or a metallic post in reversed orientation and teeth restored with light-cured composite. Survival rate of each technique was evaluated at predetermined follow-ups and data were analyzed with McNemar’s test (α = 0.05). Results: The difference in survival of restorations retained by two types of posts was not statistically significant in clinical and radiographical evaluations after 6, 12, and 18 months. The survival rate of reversed-orientated metal and glass fiber posts after 18 months was 81.1 and 67.6% respectively (p = 0.14). Conclusion: Reversed-orientated metal post did not show lower clinical survival compared with glass fiber posts in 18-month follow-up. Hence, reversed-orientated metal post can be considered as a potential method to obtain retention for composite restorations in severely decayed primary anterior teeth. How to cite this article: Vafaei A, Ranjkesh B, L0vschall H, Erfanparast L, Jafarabadi MA, Oskouei SG, Isidor F. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts. Int J Clin Pediatr Dent 2016;9(2):109-113. PMID:27365929

  8. Effects of combination therapy with captopril and nifedipine in severe or resistant hypertension.

    Science.gov (United States)

    White, W B; Viadero, J J; Lane, T J; Podesla, S

    1986-01-01

    To assess the effect of potent vasodilator therapy in patients with severe or resistant hypertension, 10 patients underwent therapy with captopril and nifedipine alone and in combination. Blood pressure (BP), heart rate, and blood chemistry values were monitored for 4 weeks during captopril monotherapy and after 8 weeks during combination therapy with captopril and nifedipine. Compared with baseline, the BP decreased during captopril monotherapy (180 +/- 11/98 +/- 7 vs. 209 +/- 16/118 +/- 12 mm Hg; P less than 0.005). After the addition of nifedipine, the BP was further reduced (148 +/- 23/85 +/- 16 mm Hg), but there was no change in heart rate. In three patients not achieving the diastolic BP goal during combination therapy with dosing every 8 hours, automatic 24-hour ambulatory BP monitoring demonstrated lack of antihypertensive control for only the last 2 to 3 hours of the dosing interval. These data demonstrate that combination therapy with captopril and nifedipine is effective in patients with severe hypertension, but frequent dosing intervals are necessary for adequate antihypertensive control.

  9. Determination of proteins by a reverse biuret method combined with the copper-bathocuproine chelate reaction.

    Science.gov (United States)

    Matsushita, M; Irino, T; Komoda, T; Sakagishi, Y

    1993-07-16

    A method of protein determination has been developed which combines the biuret reaction and the copper(I)-bathocuproine chelate reaction. Protein in the specimen forms a Cu(2+)-protein chelate complex (biuret reaction) during the first step. Excess Cu2+ is reduced to Cu+ by ascrobic acid, allowing the Cu+ to form a Cu(+)-bathocuproine chelate complex during the second step. The amount of Cu(+)-bathocuproine chelate complex formed is inversely proportional to the protein concentration. The sensitivity (epsilon = 1.4 x 10(6) 1.mol-1.cm-1 against human albumin) of this method was higher than that of the original Lowry (9.8 x 10(5)), pyrogallol red (1.0 x 10(6)) and commercially available Coomassie Brilliant Blue G.250 methods (6.7 x 10(5)). The color intensities of human gamma-globulin, human globulin (fractions IV-1 and IV-4), bovine albumin, egg albumin and horse gamma-globulin against human albumin (100%) ranged from 92 to 101%. The results obtained with the present method (y) correlated well with those determined by the biuret method (r = 0.998, y = 0.98 chi - 0.002, x = 1.31, y = 1.29 g/l) in 30 diluted sera. These results confirm that this assay is similar in sensitivity to the original Lowry method, is rapid and has similar reactivity to each of the various proteins in biological fluids.

  10. Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment

    NARCIS (Netherlands)

    Panhuizen, I. F.; Gold, S. J. A.; Buerkle, C.; Snoeck, M. M. J.; Harper, N. J. N.; Kaspers, M. J. G. H.; van den Heuvel, M. W.; Hollmann, M. W.

    2015-01-01

    This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min(-1)) vs those with normal renal function (CLCR ≥80 ml min(-1)). Sugammadex 4 mg kg(-1) was administered

  11. Fracture resistance of fiber posts: combinations of several small posts vs. standardized single post.

    Science.gov (United States)

    Porciani, Pier F; Vano, Michele; Radovic, Ivana; Goracci, Cecilia; Grandini, Simone; García-Godoy, Franklin; Ferrari, Marco

    2008-12-01

    To determine the fracture resistance of different sizes of standardized single fiber posts and the combinations of multiple small experimental posts. Single posts in three different sizes (1, 2 and 3; DT Light Posts, RTD; DT), as control, and seven different combinations of experimental small posts (Abrasive Technology), reproducing the sizes of several endodontic files were cemented in endodontic resin blocks. The combinations of small posts were made combining 2-4 small posts so as to reach the sizes of standardized DT posts. The posts were loaded at an angle of 45 degrees to the long axis of the block using a crosshead speed of 1 mm/minute until specimen failure. Ten posts/combinations were tested. Statistical analysis was performed using one-way ANOVA followed by Tamhane test for the post hoc comparisons (P fracture resistance increased when increasing the diameter of the post. The use of multiple posts resulted in fracture resistances comparable to that of the single post for two of the three diameters studied (DT1 and DT2). For the largest diameter (DT3), the use of multiple posts resulted in lower fracture resistances than did the single post.

  12. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts

    OpenAIRE

    Vafaei, Ali; Ranjkesh, Bahram; Lovschall, Henrik; Erfanparast, Leila; Jafarabadi, Mohammad A; Oskouei, Sina Ghertasi; Isidor, Flemming

    2016-01-01

    ABSTRACT Aim: The aim of this study was to compare the survival of composite resin restorations retained by glass fiber posts or reversed-orientated (upside-down) metal posts in severely decayed primary anterior teeth after 6, 12, and 18 months. Materials and methods: A total of forty-four 3- to 5-year-old children with bilateral severely decayed primary maxillary canines were included. Patients were treated under general anesthesia. After pulpectomy, an intracanal post was seated in the prim...

  13. Analysis of a Combined Antenna Arrays and Reverse-Link Synchronous DS-CDMA System over Multipath Rician Fading Channels

    National Research Council Canada - National Science Library

    Kim Yong-Seok; Whang Keum-Chan

    2005-01-01

    We present the BER analysis of antenna array (AA) receiver in reverse-link asynchronous multipath Rician channels and analyze the performance of an improved AA system which applies a reverse-link synchronous transmission technique (RLSTT...

  14. Combination of Landsat and Sentinel-2 MSI data for initial assessing of burn severity

    Science.gov (United States)

    Quintano, C.; Fernández-Manso, A.; Fernández-Manso, O.

    2018-02-01

    Nowadays Earth observation satellites, in particular Landsat, provide a valuable help to forest managers in post-fire operations; being the base of post-fire damage maps that enable to analyze fire impacts and to develop vegetation recovery plans. Sentinel-2A MultiSpectral Instrument (MSI) records data in similar spectral wavelengths that Landsat 8 Operational Land Imager (OLI), and has higher spatial and temporal resolutions. This work compares two types of satellite-based maps for evaluating fire damage in a large wildfire (around 8000 ha) located in Sierra de Gata (central-western Spain) on 6-11 August 2015. 1) burn severity maps based exclusively on Landsat data; specifically, on differenced Normalized Burn Ratio (dNBR) and on its relative versions (Relative dNBR, RdNBR, and Relativized Burn Ratio, RBR) and 2) burn severity maps based on the same indexes but combining pre-fire data from Landsat 8 OLI with post-fire data from Sentinel-2A MSI data. Combination of both Landsat and Sentinel-2 data might reduce the time elapsed since forest fire to the availability of an initial fire damage map. Interpretation of ortho-photograph Pléiades 1 B data (1:10,000) provided us the ground reference data to measure the accuracy of both burn severity maps. Results showed that Landsat based burn severity maps presented an adequate assessment of the damage grade (κ statistic = 0.80) and its spatial distribution in wildfire emergency response. Further using both Landsat and Sentinel-2 MSI data the accuracy of burn severity maps, though slightly lower (κ statistic = 0.70) showed an adequate level for be used by forest managers.

  15. Effect of quinine and artesunate combination therapy on platelet count of children with severe malaria.

    Science.gov (United States)

    Gupta, Parul; Narang, Manish; Gomber, Sunil; Saha, Rumpa

    2017-05-01

    There are several case reports of quinine-induced thrombocytopenia but no clinical trials to ascertain its incidence and significance in severe malaria. The primary objective was to assess the effect of quinine on the platelet count in children with severe malaria and to compare it with artesunate combination therapy (ACT), and the secondary objective was to assess outcome of treatment with quinine and ACT. An open-labelled, randomised, controlled trial was undertaken in 100 children aged 6 months to 12 years who were diagnosed with malaria by microscopy and/or rapid diagnostic test kits with at least one WHO clinical or laboratory criterion for severe malaria. All subjects were commenced on either quinine or ACT. Clindamycin was added to artesunate as a combination drug (ACT). It was also given to patients on quinine to avoid its confounding effect on the results. Platelet counts were undertaken every 24 hours for 7 consecutive days, temperature and coma score (Blantyre coma score ≥3 in children 4 years) was recorded 6-hourly and peripheral smears were taken 12-hourly until two consecutively negative smears were obtained. The primary outcome was a fall in the platelet count by ≥20% from the time of drug initiation until day 7. The secondary outcome was comparison of the efficacy, parasite clearance time, fever clearance time, coma recovery time and adverse effects of quinine vs ACT. 30.4% patients in the quinine group (n = 48) had ≥20% fall in platelet count and 10.8% of patients in the ACT group (n = 46) (P = 0.02). Despite the fall in platelet count, there was no bleeding. The efficacy of ACT was significantly better than quinine but the other treatment outcomes showed insignificant difference. Quinine should be used with caution in patients with severe malaria because of the potential risk of quinine-induced thrombocytopenia.

  16. Two Cases of Severe Combined Immunodeficiency Caused By Adenosine Deaminase Deficiency

    Directory of Open Access Journals (Sweden)

    Turkan Patiroglu

    2014-08-01

    Full Text Available Severe Combined Immune Deficiency (SCID is a primary immune deficiency disorder manifested with severe infections upon first months of life, which is characterized by diverse genetic defects in T and B lymphocyte functions and occasionally in NK cells. ADA deficiency is a form of SCID progressing with severe lymphopenia and immune deficiency caused by toxic metabolites of ADA. Bone marrow transplantation (BMT is the only curative treatment although prophylactic anti-microbial therapy, intravenous immunoglobulin (IVIG and enzyme replacement can achieve transient improvements. Early diagnosis before development of severe infections and organ injury and referral to pediatric immunology clinics will make considerable contributions to prognosis. Here, we presented 2 cousins with SCID who had positive family history with deceased sibling; presented with tanning at skin, severe neonatal infections and Q246X (c736C>T non-sense mutation in exon 8 in ADA gene  in order to emphasize this rare mutation and pediatric emergencies associated with this disorder.

  17. Combining spectral mixture analysis and object-based classification for fire severity mapping

    Energy Technology Data Exchange (ETDEWEB)

    Fernadez-Manso, O.; Quintano, C.; Quintano, C.; Fernandez-Manso, A.

    2009-07-01

    This study shows an accurate and fast methodology in order to evaluate fire severity classes of large forest fires. A single Landsat Enhanced Thematic Mapper multispectral image was utilized with the aim of mapping fire severity classes (high, moderate and low) using a combined-approach based in a spectral mixing model and object-based image analysis. A large wildfire in the Northwest of Spain was used to test the model. Fraction images obtained by Landsat unmixing were used as input data in the object-based image analysis. A multilevel segmentation and a classification were carried out by using membership functions. This method was compared with other simpler in order to evaluate the suitability to distinguish between the three fire severity classes above mentioned. McNemar's test was used to evaluate the statistical significance of the difference between approaches tested in this study. The combined approach achieved the highest accuracy reaching 97.32% and kappa index of agreement of 95.96% and improving accuracy of individual classes. (Author) 89 refs.

  18. A psychoanalytically oriented combined treatment approach for severely disturbed borderline patients: the Athens project.

    Science.gov (United States)

    Vaslamatzis, Grigoris; Coccossis, Maria; Zervis, Christos; Panagiotopoulou, Victoria; Chatziandreou, Maria

    2004-01-01

    A psychoanalytically oriented combined treatment is considered beneficial for severely disturbed borderline patients, especially during an acute crisis. The proposed treatment comprises hospitalization and specialized psychotherapeutic inpatient treatment, individual psychoanalytic psychotherapy, and psychiatric management. It is important to take into account that during inpatient treatment, projective identifications and splitting mechanisms are activated, involving different members of the therapeutic personnel or other patients. The mental health team--the psychiatrist, the nurses, the assigned psychotherapist, and other members of the therapeutic personnel--should work together in the context of teamwork in order to explore transference and countertransference manifestations. This function promotes empathy and understanding of the patient's inner difficulties. A combined treatment approach can help the patient stabilize his or her condition and develop awareness and motivation for undertaking long-term treatment and individual psychoanalytic psychotherapy, with the prospect that therapy will be maintained after the patient's discharge.

  19. Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats.

    Science.gov (United States)

    Happé, C M; de Raaf, M A; Rol, N; Schalij, I; Vonk-Noordegraaf, A; Westerhof, N; Voelkel, N F; de Man, F S; Bogaard, H J

    2016-06-01

    The SU5416 + hypoxia (SuHx) rat model is a commonly used model of severe pulmonary arterial hypertension. While it is known that exposure to hypoxia can be replaced by another type of hit (e.g., ovalbumin sensitization) it is unknown whether abnormal pulmonary blood flow (PBF), which has long been known to invoke pathological changes in the pulmonary vasculature, can replace the hypoxic exposure. Here we studied if a combination of SU5416 administration combined with pneumonectomy (PNx), to induce abnormal PBF in the contralateral lung, is sufficient to induce severe pulmonary arterial hypertension (PAH) in rats. Sprague Dawley rats were subjected to SuPNx protocol (SU5416 + combined with left pneumonectomy) or standard SuHx protocol, and comparisons between models were made at week 2 and 6 postinitiation. Both SuHx and SuPNx models displayed extensive obliterative vascular remodeling leading to an increased right ventricular systolic pressure at week 6 Similar inflammatory response in the lung vasculature of both models was observed alongside increased endothelial cell proliferation and apoptosis. This study describes the SuPNx model, which features severe PAH at 6 wk and could serve as an alternative to the SuHx model. Our study, together with previous studies on experimental models of pulmonary hypertension, shows that the typical histopathological findings of PAH, including obliterative lesions, inflammation, increased cell turnover, and ongoing apoptosis, represent a final common pathway of a disease that can evolve as a consequence of a variety of insults to the lung vasculature. Copyright © 2016 the American Physiological Society.

  20. Myelofibrosis in severe combined immunodeficiency due to vitamin D deficiency rickets.

    Science.gov (United States)

    al-Eissa, Y A; al-Mashhadani, S A

    1994-01-01

    An infant with severe combined immunodeficiency is described in whom a refractory anemia and thrombocytopenia developed after the age of 6 months, associated with poor growth and frequent episodes of upper respiratory tract infections and diarrhea. He required frequent blood and platelet transfusions. Bone marrow biopsy provided evidence that the anemia and thrombocytopenia were the results of myelofibrosis which was secondary to vitamin D deficiency. Therapy with 1,25-dihydroxycholecalciferol resulted in resolution of the hematologic and skeletal abnormalities, but he remained susceptible to recurrent serious infections and died at the age of 13 months.

  1. The combined benefits of motorcycle antilock braking systems (ABS) in preventing crashes and reducing crash severity.

    Science.gov (United States)

    Rizzi, Matteo; Kullgren, Anders; Tingvall, Claes

    2016-01-01

    Several studies have reported the benefits of motorcycle antilock braking systems (ABS) in reducing injury crashes, due to improved stability and braking performance. Both aspects may prevent crashes but may also reduce the crash severity when a collision occurs. However, it is still unknown to what extent the reductions in injury crashes with ABS may be due to a combination of these mechanisms. Swedish hospital and police reports (2003-2012) were used. The risk for permanent medical impairment (RPMI) was calculated, showing the risk of at least 1 or 10% permanent medical impairment. In total, 165 crashes involving ABS-equipped motorcycles were compared with 500 crashes with similar motorcycles without ABS. The analysis was performed in 3 steps. First, the reduction in emergency care visits with ABS was calculated using an induced exposure approach. Secondly, the injury mitigating effects of ABS were investigated. The mean RPMI 1+ and RPMI 10+ were analyzed for different crash types. The distributions of impairing injuries (PMI 1+) and severely impairing injuries (PMI 10+) were also analyzed. In the third step, the total reduction of PMI 1+ and PMI 10+ injured motorcyclists was calculated by combining the reductions found in the previous steps. An additional analysis of combined braking systems (CBS) together with ABS was also performed. The results showed that emergency care visits were reduced by 47% with ABS. In the second step, it was found that the mean RPMI 1+ and RPMI 10+ with ABS were 15 and 37% lower, respectively. Finally, the third step showed that the total reductions in terms of crash avoidance and mitigation of PMI 1+ and PMI 10+ injured motorcyclists with ABS were 67 and 55%, respectively. However, PMI 1+ and PMI 10+ leg injuries were not reduced by ABS to the same extent. Indications were found suggesting that the benefits of ABS together with CBS may be greater than ABS alone. This article indicated that motorcycle ABS reduced impairing injuries

  2. Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS).

    Science.gov (United States)

    Liu, Xuemei; Zhang, Mingming; He, Lin; Li, Youping

    2012-10-17

    Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by a novel coronavirus, which first appeared in Foshan City, China on 22 December 2002. Chinese herbs were used in its treatment. To evaluate the possible effectiveness and safety of Chinese herbs combined with Western medicines versus Western medicines alone for SARS patients. We searched CENTRAL 2012, Issue 3, MEDLINE (1966 to February Week 4, 2012), EMBASE (1990 to March 2012) and the Chinese Biomedical Literature (Issue 3, 2012). Randomised controlled trials (RCTs) and quasi-RCTs of Chinese herbs combined with Western medicines versus Western medicines alone for patients diagnosed with SARS. Two review authors (XL, MZ) independently extracted trial data. We extracted dichotomous and continuous data with 95% confidence intervals (CI). For dichotomous data, we used risk ratio (RR). For continuous data, we calculated mean differences (MD). We calculated overall results based on the random-effects model if heterogeneity existed between studies. If no heterogeneity was detected between the studies, we used the fixed-effect model. We used the Z score and the Chi(2) test with significance being set at P herbs were identified. We did not find Chinese herbs combined with Western medicines decreased mortality versus Western medicines alone. Two herbs may improve symptoms. Five herbs may improve lung infiltrate absorption. Four herbs may decrease the dosage of corticosteroids. Three herbs may improve the quality of life of SARS patients. One herb may shorten the length of hospital stay. Chinese herbs combined with Western medicines made no difference in decreasing mortality versus Western medicines alone. It is possible that Chinese herbs combined with Western medicines may improve symptoms, quality of life and absorption of pulmonary infiltration, and decrease the corticosteroid dosage for SARS patients. The evidence is weak because of the poor quality of the included trials. Long-term follow

  3. Endodontic and periodontal management of a severely affected maxillary lateral incisor having combined mucosal fenestration and palatogingival groove

    National Research Council Canada - National Science Library

    Sharma, Sarang; Srivastava, Dhirendra; Sood, Vishal; Yadav, Priya

    2015-01-01

    .... Coexistent fenestration defect and palato gingival groove in the same tooth is extremely rare and undoubtedly is a perfect combination to precipitate severe endodontic-periodontal consequences...

  4. Detoxification combining fasting with fluid therapy for refractory cases of severe atopic dermatitis.

    Science.gov (United States)

    Kim, Kyu Seok; Nam, Hae Jeong

    2013-01-01

    To introduce and determine the clinical benefits of a detoxification program that combines fasting with fluid therapy for refractory cases of severe atopic dermatitis (AD), we performed a retrospective chart review of inpatients with AD from March 2010 to February 2012 at the Department of Ophthalmology, Otorhinolaryngology and Dermatology of Korean Medicine in the Kyung Hee Medical Center. Patients were treated with the detoxification program, which combined fasting with fluid therapy, and herbal medicine, herbal wet wrap dressings, or acupuncture treatment when clinically necessary. The primary outcome was the SCORAD total index. The secondary outcome was the pruritus visual analogue scale (VAS) score in SCORAD as evaluated by a trained dermatology specialist. Among the 130 inpatients that have done detoxification, 7 patients met the inclusion criteria. The mean total SCORAD scores significantly decreased from 64.67 ± 11.72 to 26.26 ± 11.01 (P = 0.018) after the detoxification program. There was also a significant decrease in VAS score for pruritus from 8.00 ± 1.16 to 2.57 ± 0.98 (P = 0.016) between admission and discharge. We suggest that fasting with fluid therapy as a complementary and alternative treatment method may provide some benefits for patients with refractory cases of severe atopic dermatitis.

  5. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

    Directory of Open Access Journals (Sweden)

    Claudia A Montiel-Equihua

    2009-12-01

    Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial

  6. Combined Occurrence of Autosomal Dominant Aniridia and Autosomal Recessive Albinism in Several Members of a Family.

    Science.gov (United States)

    Yahalom, Claudia; Sharon, Dror; Dalia, Eli; Simhon, Shiran Ben; Shemesh, Efrat; Blumenfeld, Anat

    2015-06-01

    To characterize clinical and genetic aspects of a family with a unique combination of two hereditary blinding eye diseases. Comprehensive eye examination of proband and family members. Molecular analyses of the TYR and PAX6 genes. A young couple, both legally blind, requested genetic counselling regarding their ocular condition. The female was previously diagnosed with oculocutaneous albinism (OCA1A) and her spouse was diagnosed with Peters anomaly. A comprehensive clinical examination revealed that the female had OCA1A combined with signs of another ocular disease, showing some similarity to aniridia. A complete ocular examination of her family members revealed that her brother also suffered from the same combined phenotype, her father had typical OCA1A signs, and her mother and sister had aniridia-like phenotype, without clinical diagnosis until the time of presentation. Molecular analysis identified two compound heterozygous TYR mutations known to cause OCAIA and cosegregate with oculocutaneous albinism. In addition, we identified a novel heterozygous PAX6 mutation confirming the atypical aniridia phenotype. We report here a unique and rare clinical phenotype that is explained by the segregation of two severe inherited eye diseases. The clinical and genetic analysis in this family allowed them to receive accurate genetic counseling.

  7. Clinical dimensions of fibromyalgia symptoms and development of a combined index of severity: the CODI index.

    Science.gov (United States)

    Cuesta-Vargas, Antonio; Luciano, Juan V; Peñarrubia-María, Maria Teresa; García-Campayo, Javier; Fernández-Vergel, Rita; Arroyo-Morales, Manuel; Serrano-Blanco, Antoni

    2013-02-01

    Although a large body of work indicates that fibromyalgia (FM) is not a discrete entity, few studies have attempted to classify the heterogeneity of FM symptoms. The objectives of the present study were to confirm the existence of two latent dimensions underlying FM symptoms (Core-FM symptoms and Distress) by means of factor analysis techniques, and to develop and validate a new combined index of symptom severity (the CODI). We analyzed and combined the baseline scores on six visual analog scales of the FIQ (pain, general fatigue, morning fatigue, stiffness, anxiety, and depression) and on the STAI-T (trait anxiety) of 216 Spanish patients diagnosed with FM (97.7% women) who were participating in a randomized, controlled trial. The principal component analysis indicated the presence of two correlated factors (labeled as Core-FM symptoms and Distress) that explained 64% of total variance. The subsequent confirmatory factor analysis yielded more empirical support for the two-factor model than the one-factor model (all items loading on one latent dimension). The two factors possessed adequate internal consistency and construct validity given the pattern of significant correlations with the Euroqol items. The Core-FM dimension had a stronger relationship with mobility, self-care, usual activities, and pain/discomfort than with anxiety/depression, whereas the Distress dimension showed the opposite pattern. Finally, summing the standardized scores of the two dimensions, a new combined index of symptom severity (the CODI) was developed. The clinical implications and utility of the CODI are discussed in relation to previous research on FM.

  8. Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness.

    Science.gov (United States)

    Wang, Zheng; Zhang, Junli; Li, Fan; Ji, Xiaolin; Liao, Lingjie; Ma, Liying; Xing, Hui; Feng, Yi; Li, Dan; Shao, Yiming

    2017-04-02

    Fitness is a key parameter in the measurement of transmission capacity of individual drug-resistant HIV. Drug-resistance related mutations (DRMs) T369V/I and A371V in the connection subdomain (CN) of reverse transcriptase (RT) occur at higher frequencies in the individuals experiencing antiretroviral therapy failure. Here, we evaluated the effects of T369V/I and A371V on viral fitness, in the presence or in the absence of thymidine analogue resistance-associated mutations (TAMs) and assessed the effect of potential RT structure-related mechanism on change in viral fitness. Mutations T369V/I, A371V, alone or in combination with TAMs were introduced into a modified HIV-1 infectious clone AT1 by site-directed mutagenesis. Then, experiments on mutant and wild-type virus AT2 were performed separately using a growth-competition assay, and then the relative fitness was calculated. Structural analysis of RT was conducted using Pymol software. Results showed that T369V/I severely impaired the relative virus fitness, and A371V compensated for the viral fitness reduction caused by TAMs. Structural modeling of RT suggests that T369V/I substitutions disrupt powerful hydrogen bonds formed by T369 and V365 in p51 and p66. This study indicates that the secondary DRMs within CN might efficiently damage viral fitness, and provides valuable information for clinical surveillance and prevention of HIV-1 strains carrying these DRMs. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Xenon Combined with Therapeutic Hypothermia Is Not Neuroprotective after Severe Hypoxia-Ischemia in Neonatal Rats.

    Directory of Open Access Journals (Sweden)

    Hemmen Sabir

    Full Text Available Therapeutic hypothermia (TH is standard treatment following perinatal asphyxia in newborn infants. Experimentally, TH is neuroprotective after moderate hypoxia-ischemia (HI in seven-day-old (P7 rats. However, TH is not neuroprotective after severe HI. After a moderate HI insult in newborn brain injury models, the anesthetic gas xenon (Xe doubles TH neuroprotection. The aim of this study was to examine whether combining Xe and TH is neuroprotective as applied in a P7 rat model of severe HI.120 P7 rat pups underwent a severe HI insult; unilateral carotid artery ligation followed by hypoxia (8% O2 for 150min at experimental normothermia (NT-37: Trectal 37°C. Surviving pups were randomised to immediate NT-37 for 5h (n = 36, immediate TH-32: Trectal 32°C for 5h (n = 25 or immediate TH-32 plus 50% inhaled Xe for 5h (n = 24. Pups were sacrificed after one week of survival. Relative area loss of the ligated hemisphere was measured, and neurons in the subventricular zone of this injured hemisphere were counted, to quantify brain damage.Following the HI insult, median (interquartile range, IQR hemispheric brain area loss was similar in all groups: 63.5% (55.5-75.0 for NT-37 group, 65.0% (57.0-65.0 for TH-32 group, and 66.5% (59.0-72.0 for TH-32+Xe50% group (not significant. Correspondingly, there was no difference in neuronal cell count (NeuN marker in the subventricular zone across the three treatment groups.Immediate therapeutic hypothermia with or without additional 50% inhaled Xe, does not provide neuroprotection one week after severe HI brain injury in the P7 neonatal rat. This model aims to mimic the clinical situation in severely asphyxiated neonates and treatment these newborns remains an ongoing challenge.

  10. A combined approach of amniotic membrane and oral mucosa transplantation for fornix reconstruction in severe symblepharon.

    Science.gov (United States)

    Kheirkhah, Ahmad; Ghaffari, Reza; Kaghazkanani, Reza; Hashemi, Hassan; Behrouz, Mahmoud Jabbarvand; Raju, Vadrevu K

    2013-02-01

    To evaluate the results of a combined approach of cicatrix lysis, intraoperative mitomycin C (MMC) application, oral mucosal transplantation (OMT), and amniotic membrane transplantation (AMT) for surgery of severe symblepharon. This prospective study included 32 eyes with severe symblepharon in which after cicatrix lysis the residual conjunctiva was not enough to cover the tarsus (grade III symblepharon) or there was no residual conjunctiva (grade IV symblepharon). After symblepharon lysis and MMC application, OMT was used to cover the tarsus throughout to fornix, and AMT with fibrin glue was performed to cover the exposed sclera. Outcome was defined as complete success (restoration of an anatomically deep fornix), partial success (focal recurrence of scar), or failure (return of symblepharon). Etiology of symblepharon included chemical burn (n = 16), thermal burn (n = 7), Stevens-Johnson syndrome (n = 5), mucous membrane pemphigoid (n = 2), xeroderma pigmentosum (n = 1), and graft-versus-host disease (n = 1). Motility restriction was present in 87.5% preoperatively. After a mean follow-up of 16.4 ± 7.6 months, the anatomical outcome included complete success in 84.4%, partial success in 9.4%, and failure in 6.2%. In grades III and IV symblephara, the outcomes were complete success in 89.5% and 76.9%, partial success in 10.5% and 7.7%, and failure in none and 15.4%, respectively. No motility restriction was noted in any eye postoperatively. Complications included entropion (n = 2), ocular surface keratinization (n = 1), and pyogenic granuloma (n = 4). In severe symblepharon, a combined approach of cicatrix lysis, MMC application, OMT, and sutureless AMT was a safe and effective technique for fornix reconstruction.

  11. Combined analysis of trabectome and phaco-trabectome outcomes by glaucoma severity

    Science.gov (United States)

    Bussel, Igor I.; Loewen, Ralitsa T.; Parikh, Hardik; Loewen, Nils A.

    2016-01-01

    Prior glaucoma severity staging systems were mostly concerned with visual field function and retinal nerve fiber layer, but did not include intraocular pressure or medications to capture resistance to treatment. We recently introduced a simple index that combines pressure, medications, and visual field damage and applied it to stratify outcomes of trabectome surgery. In the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery. This microincisional glaucoma surgery removes the primary resistance to outflow in glaucoma, the trabecular meshwork, and has been mostly used in mild glaucoma. Traditional glaucoma surgeries have a relatively high complication rate and have been reserved for more advanced disease stages. In the analysis presented here we include our data of trabectome combined with cataract surgery. This is a common practice pattern as both occur in the same age group with increasing frequency. For patients in higher glaucoma index (GI) groups, the intraocular pressure (IOP) reduction was 2.34+/-0.19 mmHg more than those in a GI group one level lower while holding everything else constant. Those who had undergone trabectome combined with phacoemulsification had an IOP reduction that was 1.29+/-0.39 mmHg less compared to those with trabectome alone. No statistically significant difference was found between genders and age groups while holding everything else constant. Hispanics had a 3.81+/-1.08 mmHg greater IOP reduction. Pseudoexfoliation and steroid glaucoma patients had an IOP reduction that was greater by 2.91+/-0.56 and 3.86+/-0.81 mmHg, respectively, than those with primary open angle glaucoma. These results suggest a role for trabectome-mediated ab interno trabeculectomy beyond mild forms of glaucoma. Additionally, the multifactorial glaucoma index demonstrates a role in staging patients when comparing glaucoma surgical modalities. PMID

  12. Haptically facilitated bimanual training combined with augmented visual feedback in moderate to severe hemiplegia

    Science.gov (United States)

    Boos, Amy; Qiu, Qinyin; Fluet, Gerard G.; Adamovich, Sergei V.

    2015-01-01

    This study describes the design and feasibility testing of a hand rehabilitation system that provides haptic assistance for hand opening in moderate to severe hemiplegia while subjects attempt to perform bilateral hand movements. A cable-actuated exoskeleton robot assists the subjects in performing impaired finger movements but is controlled by movement of the unimpaired hand. In an attempt to combine the neurophysiological stimuli of bilateral movement and action observation during training, visual feedback of the impaired hand is replaced by feedback of the unimpaired hand, either by using a sagittaly oriented mirror or a virtual reality setup with a pair of virtual hands presented on a flat screen controlled with movement of the unimpaired hand, providing a visual image of their paretic hand moving normally. Joint angles for both hands are measured using data gloves. The system is programmed to maintain a symmetrical relationship between the two hands as they respond to commands to open and close simultaneously. Three persons with moderate to severe hemiplegia secondary to stroke trained with the system for eight, 30 to 60 minute sessions without adverse events. Each demonstrated positive motor adaptations to training. The system was well tolerated by persons with moderate to severe upper extremity hemiplegia. Further testing of its effects on motor ability with a broader range of clinical presentations is indicated. PMID:22254998

  13. Hematological changes in severe early onset growth-restricted fetuses with absent and reversed end-diastolic flow in the umbilical artery.

    Science.gov (United States)

    Bahlmann, Franz; Al Naimi, Ammar; Ossendorf, Manfred; Schmidt-Fittschen, Monica; Willruth, Arne

    2017-04-01

    Erythropoietin seems to play an important role in the regulation of fetal hypoxemia. The present prospective study was designed to determine if changes in erythropoietin levels can be found in fetuses with severe early-onset growth restriction and hemodynamic compromise. Erythropoietin, hemoglobin, hematocrit, platelet counts, normoblasts, lacate, arterial and venous blood gasses in the umbilical cord were determined in 42 fetuses with fetal growth restriction (IUGR) with absent (zero-flow) and 26 IUGR fetuses with retrograde end-diastolic flow (reverse-flow) in the umbilical artery. Color Doppler measurements were performed on the middle cerebral artery (PI) and ductus venosus [(S-a)/D and (S-a)/Vmean]. Erythropoietin concentrations were significantly lower in the zero-flow group (median: 128.0 mU/mL; range: 60.3-213 mU/mL) compared with the reverse-flow group (median: 202.5 mU/mL; range: 166-1182 mU/mL). Significant differences in median lactate concentrations were observed between the zero-flow group: 3.28 mmol/L (range; 2.3-4.7 mmol/L), and reverse-flow group: 5.6 mmol/L (range: 3.8-7.5 mmol/L). Fetuses with reverse-flow had significantly lower median platelet counts than fetuses with zero-flow (74 vs. 155/μL) and significantly lower normoblast counts (63 vs. 342/100 WBC). Fetuses with severe IUGR due to chronic placental insufficiency and absent or reversed flow in the umbilical artery show increased erythropoietin levels.

  14. Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Bruyand, Mathias; Ryom, Lene; Shepherd, Leah

    2015-01-01

    BACKGROUND: The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS: Participants were followed from the latest of D:A:D study entry...... or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non...... diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1...

  15. Cost-effectiveness of roflumilast in combination with bronchodilator therapies in patients with severe and very severe COPD in Switzerland

    Directory of Open Access Journals (Sweden)

    Samyshkin Y

    2013-01-01

    Full Text Available Yevgeniy Samyshkin,1 Michael Schlunegger,2 Susan Haefliger,3 Sabine Ledderhose,3 Matthew Radford11IMS Health, Health Economics and Outcomes Research, London, United Kingdom; 2Marketing Specialty Care, 3Medical Department, Takeda Pharma AG, Pfäffikon, SwitzerlandObjective: Chronic obstructive pulmonary disease (COPD represents a burden on patients and health systems. Roflumilast, an oral, selective phosphodiesterase-4-inhibitor reduces exacerbations and improves lung function in severe/very severe COPD patients with a history of exacerbations. This study aimed to estimate the lifetime cost and outcomes of roflumilast added-on to commonly used COPD regimens in Switzerland.Methods: A Markov cohort model was developed to simulate COPD progression in patients with disease states of severe, very severe COPD, and death. The exacerbation rate was assumed to be two per year in severe COPD. COPD progression rates were drawn from the published literature. Efficacy was expressed as relative ratios of exacerbation rates associated with roflumilast, derived from a mixed-treatment comparison. A cost-effectiveness analysis was conducted for roflumilast added to long-acting muscarinic antagonists (LAMA, long-acting ß2-agonist/inhaled corticosteroids (LABA/ICS, and LAMA + LABA/ICS. The analysis was conducted from the Swiss payer perspective, with costs and outcomes discounted at 2.5% annually. Parameter uncertainties were explored in one-way and probabilistic sensitivity analyses.Results: In each of the comparator regimens mean life expectancy was 9.28 years and quality-adjusted life years (QALYs gained were 6.19. Mean estimated lifetime costs per patient in the comparator arms were CHF 83,364 (LAMA, CHF 88,161 (LABA/ICS, and CHF 95,564 (LAMA + LABA/ICS respectively. Adding roflumilast resulted in a mean cost per patient per lifetime of CHF 86,754 (LAMA + roflumilast, CHF 91,470 (LABA/ICS + roflumilast, and CHF 99,364 (LAMA + LABA/ICS + roflumilast

  16. Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

    Directory of Open Access Journals (Sweden)

    Pergolizzi Jr JV

    2012-08-01

    enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with minimal toxicity.Keywords: NSAIDs, opioids, combination analgesics, moderate pain, severe pain, analgesics, tramadol/paracetamol

  17. Neonatal Screening for Severe Combined Immune Deficiency in Russia: Glorious Future or Tomorrow’s Reality?

    Directory of Open Access Journals (Sweden)

    Svetlana S. Deryabina

    2017-01-01

    Full Text Available Mass screening of newborns in Russia for five hereditary diseases does not meet the requirements of the world community for the neonatal screening program. Success in the development of laboratory diagnostic technologies and active introduction of achievements in genetics and molecular biology into medical practice allow for the revision of the list of nosologies included in the national neonatal screening program by replacing the disease or adding new nosologies. The article discusses the possibility of including genetic testing for severe combined immune deficiency in the Newborn Screening Program in Russia. The results from a retrospective study of markers of naive T- and B-lymphocytes (TREC and KREC in the group of children with immuno-dependent pathology developed in the first year of life are discussed.

  18. Abnormal in vitro thymocyte differentiation in a patient with severe combined immunodeficiency-Nezelof`s syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Knutsen, A.P.; Wall, D.; Mueller, K.R.; Bouhasin, J.D. [Pediatric Research Institute, St. Louis, MO (United States)

    1996-05-01

    An in vitro coculture model system of CD34+ stem cells and allogenic cultured thymic epithelia fragments was used to evaluate thymocyte differentiation in a 9-month-old child of Amish descent with Nezelof syndrome. Though the patient`s stem cells differentiate to acquire normal expression of CD2 and CD7, later steps of maturation were abnormal. There was detectable but reduced expression of CD3 and CD4 phenotypes. CD44+ expression, however, was markedly reduced. CD44 is an adhesion molecule, interacting with the matrix ligands hyaluronan and fibronectin, and is expressed early in thymocyte differentiation and subsequently in mature T cells. It is hypothesized that abnormal expression of CD44 in a variant of severe combined immunodeficiency, Nezelof`s syndrome, interferes with normal thymocyte and thymic epithelial interaction, which leads to abnormal thymocyte differentiation. 35 refs., 2 figs., 3 tabs.

  19. A Call to Include Severe Combined Immunodeficiency in Newborn Screening Program

    Directory of Open Access Journals (Sweden)

    Raz Somech

    2014-01-01

    Full Text Available Quantification of the T cell receptor excision circles (TRECs has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.

  20. A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens D; Pedersen, Court

    2003-01-01

    BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ....037. CONCLUSION: A regimen of nelfinavir/nevirapine had a favourable virological effect and tolerability over a 48-week period compared with ritonavir/saquinavir, when administered in combination with two nucleoside reverse transcriptase inhibitors. However, more extensive follow-up is required to determine...

  1. Pulse therapy combined with oral corticosteroids in the management of severe rheumatic carditis and rebound.

    Science.gov (United States)

    Torres, Renato P A; Torres, Rômulo F A; Torres, Rafael A; Torres, Rosângela S L A

    2017-10-25

    The aim of the present study was to describe the clinical course, laboratory tests, and the cardiac involvement in rheumatic carditis patients in functional class III and IV, submitted to pulse therapy combined with oral prednisone. A total of 120 patients with severe carditis due to acute rheumatic fever were treatment with three cycles of pulse therapy combined with oral corticosteroids. The patients were followed up from the hospital admission until the end of the treatment and returned after 30, 60, and 90 days to control. The patients were evaluated by clinical, laboratory, and transthoracic echocardiogram. In total, 23 (19.2%) patients at first attack of rheumatic fever and 97 (80.8%) with recurrent carditis were evaluated. Cardiac surgery was performed in 8 (6.6%) patients. The patients showed improved laboratory and radiological parameters (prheumatic carditis and the oral corticosteroid prevented rebound episodes. Prolonged hospital stay was required for the clinical stabilisation of patients and to avoid the interruption of medication.

  2. Combining several thermal indices to generate a unique heat comfort assessment methodology

    Directory of Open Access Journals (Sweden)

    Wissam EL Hachem

    2015-11-01

    Full Text Available Purpose: The proposed methodology hopes to provide a systematic multi-disciplinary approach to assess the thermal environment while minimizing unneeded efforts. Design/methodology/approach: Different factors affect the perception of the human thermal experience: metabolic rate (biology, surrounding temperatures (heat balance and environmental factors and cognitive treatment (physiology.This paper proposes a combination of different multidisciplinary variables to generate a unique heat comfort assessment methodology. The variables at stake are physiological, biological, and environmental. Our own heat analysis is thoroughly presented and all relevant equations are described. Findings: Most companies are oblivious about potential dangers of heat stress accidents and thus about methods to monitor and prevent them. This methodology enables the company or the concerned individual to conduct a preliminary assessment with minimal wasted resources and time in unnecessary steps whilst providing a guideline for a detailed study with minimal error rates if needed. More so, thermal comfort is an integral part of sound ergonomics practices, which in turn are decisive for the success of any lean six sigma initiative. Research limitations/implications: This methodology requires several full implementations to finalize its design. Originality/value: Most used heat comfort models are inherently uncertain and tiresome to apply. An extensive literature review confirms the need for a uniform assessment methodology that combines the different thermal comfort models such as the Fanger comfort model (PMV, PPD and WGBT since high error rates coupled with tiresome calculations often hinder the thermal assessment process.

  3. A reversed phase liquid chromatographic method for the simultaneous determination of several common penicillins in human serum.

    Science.gov (United States)

    Mendez-Alvarez, E; Soto-Otero, R; Sierra-Paredes, G; Aguilar-Veiga, E; Galan-Valiente, J; Sierra-Marcuño, G

    1991-03-01

    A rapid and sensitive high performance liquid chromatographic method is described for the simultaneous determination of benzylpenicillin, ampicillin, phenoxymethylpenicillin, cloxacillin, dicloxacillin and nafcillin in small samples of human serum. The chromatographic system involves the use of a Spherisorb ODS reversed phase column and a gradient elution with 1 mM ammonium acetate buffer/acetonitrile (from 90:10 to 75:25 in 15 min). Detection and quantification are monitored by UV absorption at 208 nm. The compounds are extracted with dichloromethane, using tetrabutylammonium hydrogen sulfate neutralized with sodium hydroxide and buffered with borate as an ion pairing reagent; beta-hydroxyethyltheophylline is added as an internal standard. Our results show that the method is accurate and reproducible, allowing quantification of serum levels of assayed penicillins (0.5-50 micrograms/mL) without interference from other drugs commonly used in therapy. Recoveries were generally greater than 79.4%.

  4. A Synoptic Climatology of Combined Severe/Weather/Flash Flood Events

    Science.gov (United States)

    Pallozzi, Kyle J.

    Classical forms of severe weather such as tornadoes, damaging convective wind gusts, and large hail, as well as flash flooding events, all have potentially large societal impacts. This impact is further magnified when these hazards occur simultaneously in time and space. A major challenge for operational forecasters is how to accurately predict the occurrence of combined storm hazards, and how to communicate the associated multiple threat hazards to the public. A seven-year climatology (2009-2015) of combined severe weather/flash flooding (SVR/FF) events across the contiguous United States was developed in attempt to study the combined SVR/FF event hazards further. A total of 211 total cases were identified and sub-divided into seven subcategories based on their convective morphology and meteorological characteristics. Heatmaps of event report frequency were created to extract spatial, seasonal and interannual patterns in SVR/FF event activity. Diurnal trends were examined from time series plots of tornado, hail, wind and flash flood/flood reports. Event-centered composites of environmental variables were created for each subcategory from 13 km RUC/RAP analyses. Representative cases studies were conducted for each subcategory. A "ring of fire" with the highest levels of SVR/FF event activity was noted across the central United States. SVR/FF events were least common in the Southeast, High Plains, and Northern Plains. Enhanced SVR/FF activity reflected contributions from synoptic events during the cool and shoulder seasons over the Lower Mississippi, Arkansas and Tennessee Valleys, and MCS activity during the warm season over the lower Great Plains, and the Upper Mississippi, Missouri and Ohio River Valleys. Results from the composite analyses indicated that relatively high values of CAPE, surface-500 hPa shear and precipitable water were observed for all subcategories. Case studies show that many high-end SVR/FF events featured slow-moving, or quasi

  5. Combined conservative treatment and lymphatic venous anastomosis for severe lower limb lymphedema with recurrent cellulitis.

    Science.gov (United States)

    Mihara, Makoto; Hara, Hisako; Tsubaki, Hiromi; Suzuki, Takiko; Yamada, Naomi; Kawahara, Mari; Murai, Noriyuki

    2015-08-01

    Lymphedema may be treated either conservatively or surgically. Although conservative therapy is the first-line treatment, some patients are refractory to it and repeat severe cellulitis. We usually perform lymphaticovenous anastomosis (LVA) for lymphedema patients, and LVA can reduce the frequency of cellulitis. A 67-year-old woman who had undergone a radical hysterectomy, pelvic lymphadenectomy, and postoperative radiotherapy for cervical cancer at the age 50 years. She developed lymphedema in both legs, and high-pressure compression stockings caused lymphorrhea in the groin and thigh, resulting in recurrent episodes of cellulitis. Lymphoscintigraphy revealed dilation of the lymphatic vessels in both legs. Results of an indocyanine green test revealed dermal backflow throughout the lower body. After wearing low-pressure stocking, we performed LVA to reduce cellulitis. After confirming the result of LVA, the patients started wearing high-pressure stocking. The patient underwent a subsequent LVA, 3 months after the first, to further improve edema. The lymphorrhea resolved, and cellulitis did not recur. The combination of surgical treatment and conservative treatment is important for severe lymphedema treatment. Although conservative treatment is usually said to be the first-line treatment, LVA can antecede in cases refractory to conservative treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study

    NARCIS (Netherlands)

    Bruyand, Mathias; Ryom, Lene; Shepherd, Leah; Fatkenheuer, Gerd; Grulich, Andrew; Reiss, Peter; de Wit, Stéphane; D Arminio Monforte, Antonella; Furrer, Hansjakob; Pradier, Christian; Lundgren, Jens; Sabin, Caroline; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Franquet, X.; Ryom, L.; Sabin, C. A.; Kamara, D.; Smith, C.; Phillips, A.; Mocroft, A.; Tverland, J.; Mansfeld, M.; Nielsen, J.; Raben, D.; Lundgren, J. D.; Salbøl Brandt, R.; Rickenbach, M.; Fanti, I.; Krum, E.; Hillebregt, M.; Geffard, S.; Sundström, A.; Delforge, M.; Fontas, E.; Torres, F.; McManus, H.; Wright, S.; Kjær, J.; Sjøl, A.; Meidahl, P.; Helweg-Larsen, J.; Schmidt Iversen, J.; Kirk, O.; Ross, M.; Fux, C. A.; Morlat, P.; Moranne, O.; Kesselring, A. M.; Kamara, D. A.; Weber, R.; Pradier, C.; Friis-Møller, N.; Kowalska, J.; Sabin, C.; Law, M.; d'Arminio Monforte, A.; Dabis, F.; Bruyand, M.; Bower, M.; Fätkenheuer, G.; Donald, A.; Grulich, A.; Zaheri, S.; Gras, L.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; van der Poll, T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Pajkrt, D.; Bos, J. C.; van der Valk, M.; Grijsen, M. L.; Wiersinga, W. J.; Goorhuis, A.; Hovius, J. W. R.; Lowe, S.; Oude Lashof, A.; Posthouwer, D.; Pronk, M. J. H.; Ammerlaan, H. S. M.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; Nouwen, J. L.; Verbon, A.; Rijnders, B. J. A.; van Gorp, E. C. M.; van der Feltz, M.; Driessen, G. J. A.; van Rossum, A. M. C.; Branger, J.; Schippers, E. F.; van Nieuwkoop, C.; van Elzakker, E. P.; Groeneveld, P. H. P.; Bouwhuis, J. W.; Soetekouw, R.; ten Kate, R. W.; Kroon, F. P.; van Dissel, J. T.; Arend, S. M.; de Boer, M. G. J.; Jolink, H.; ter Vollaard, H. J. M.; Bauer, M. P.; den Hollander, J. G.; Pogany, K.; van Twillert, G.; Kortmann, W.; Cohen Stuart, J. W. T.; Diederen, B. M. W.; Leyten, E. M. S.; Gelinck, L. B. S.; Kootstra, G. J.; Delsing, C. E.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van den Berk, G. E. L.; van Kasteren, M. E. E.; Brouwer, A. E.; Veenstra, J.; Lettinga, K. D.; Mulder, J. W.; Vrouenraets, S. M. E.; Lauw, F. N.; van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Doedens, R.; Scholvinck, E. H.; van Assen, S.; Bierman, W. F. W.; Koopmans, P. P.; Keuter, M.; van der Ven, A. J. A. M.; ter Hofstede, H. J. M.; Dofferhoff, A. S. M.; Warris, A.; van Crevel, R.; Hoepelman, A. I. M.; Mudrikova, T.; Schneider, M. M. E.; Ellerbroek, P. M.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, M. W. M.; Barth, R. E.; van Agtmael, M. A.; Perenboom, R. M.; Claessen, F. A. P.; Bomers, M.; Peters, E. J. G.; Geelen, S. P. M.; Wolfs, T. F. W.; Bont, L. J.; Richter, C.; van der Berg, J. P.; Gisolf, E. H.; van den Berge, M.; Stegeman, A.; van Vonderen, M. G. A.; van Houte, D. P. F.; Weijer, S.; el Moussaoui, R.; Winkel, C.; Muskiet, F.; Durand, N. N.; Voigt, R.; Bonnet, F.; Breilh, D.; Dupon, M.; Chêne, G.; Fleury, H.; Malvy, D.; Mercié, P.; Pellegrin, I.; Neau, D.; Pellegrin, J. L.; Thiébaut, R.; Bouchet, S.; Gaborieau, V.; Lacoste, D.; Tchamgoué, S.; Lawson-Ayayi, S.; Wittkop, L.; Bernard, N.; Hessamfar, M.; Vandenhende, M. A.; Dauchy, F. A.; Dutronc, H.; Longy-Boursier, M.; Duffau, P.; Schmeltz, J. Roger; Pistone, T.; Receveur, M. C.; Cazanave, C.; Ochoa, A.; Vareil, M. O.; Viallard, J. F.; Greib, C.; Lazaro, E.; Lafon, M. E.; Reigadas, S.; Trimoulet, P.; Molimard, M.; Titier, K.; Moreau, J. F.; Haramburu, F.; Miremont-Salamé, G.; Dupont, A.; Gerard, Y.; Caunègre, L.; André, K.; Bonnal, F.; Farbos, S.; Gemain, M. C.; Ceccaldi, J.; de Witte, S.; Courtault, C.; Monlun, E.; Lataste, P.; Meraud, J. P.; Chossat, I.; Blaizeau, M. J.; Conte, V.; Decoin, M.; Delaune, J.; Delveaux, S.; Diarra, F.; D'Ivernois, C.; Frosch, A.; Hanappier, C.; Lenaud, E.; Leleux, U.; Le Marec, F.; Leray, J.; Louis, I.; Palmer, G.; Pougetoux, A.; Sicard, X.; Touchard, D.; Uwamaliya-Nziyumvira, B.; Petoumenos, K.; Bendall, C.; Moore, R.; Edwards, S.; Hoy, J.; Watson, K.; Roth, N.; Nicholson, J.; Bloch, M.; Franic, T.; Baker, D.; Vale, R.; Carr, A.; Cooper, D.; Chuah, J.; Ngieng, A.; Nolan, D.; Skett, J.; Calvo, G.; Mateu, S.; Domingo, P.; Sambeat, M. A.; Gatell, J.; del Cacho, E.; Cadafalch, J.; Fuster, M.; Codina, C.; Sirera, G.; Vaqué, A.; de Wit, S.; Clumeck, N.; Necsoi, C.; Gennotte, A. F.; Gerard, M.; Kabeya, K.; Konopnicki, D.; Libois, A.; Martin, C.; Payen, M. C.; Semaille, P.; van Laethem, Y.; Neaton, J.; Bartsch, G.; El-Sadr, W. M.; Thompson, G.; Wentworth, D.; Luskin-Hawk, R.; Telzak, E.; Abrams, D. I.; Cohn, D.; Markowitz, N.; Arduino, R.; Mushatt, D.; Friedland, G.; Perez, G.; Tedaldi, E.; Fisher, E.; Gordin, F.; Crane, L. R.; Sampson, J.; Baxter, J.; Cozzi-Lepri, A.; Grint, D.; Podlekareva, D.; Peters, L.; Reekie, J.; Fischer, A. H.; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Ostergaard, L.; Zilmer, K.; Smidt, Jelena; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Rockstroh, J.; Schmidt, R.; van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Staszewski, S.; Bickel, Markus; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Panos, G.; Filandras, A.; Karabatsaki, E.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; Hassoun, G.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Chirianni, A.; Montesarchio, E.; Gargiulo, M.; Antonucci, G.; Testa, A.; Narciso, P.; Vlassi, C.; Zaccarelli, M.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Zeltina, I.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Horban, A.; Bakowska, E.; Grzeszczuk, A.; Flisiak, R.; Boron-Kaczmarska, A.; Pynka, M.; Parczewski, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Doroana, M.; Caldeira, L.; Mansinho, K.; Maltez, F.; Duiculescu, D.; Rakhmanova, A.; Zakharova, N.; Buzunova, S.; Jevtovic, D.; Mokráš, M.; Tomazic, J.; González-Lahoz, J.; Soriano, V.; Labarga, P.; Medrano, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miró, J. M.; Gutierrez, M.; Mateo, G.; Karlsson, A.; Flamholc, L.; Ledergerber, B.; Francioli, P.; Cavassini, M.; Hirschel, B.; Boffi, E.; Furrer, H.; Battegay, M.; Elzi, L.; Kravchenko, E.; Chentsova, N.; Frolov, V.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A. M.; Mercey, D.; Johnson, M. A.; Murphy, M.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.; Morfeldt, L.; Thulin, G.; Åkerlund, B.; Koppel, K.; Håkangård, C.; Moroni, M.; Angarano, G.; Antinori, A.; Armignacco, O.; Castelli, F.; Cauda, R.; Di Perri, G.; Iardino, R.; Ippolito, G.; Perno, C. F.; von Schloesser, F.; Ceccherini-Silberstein, F.; Girardi, E.; Lo Caputo, S.; Andreoni, M.; Ammassari, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, R.; Cingolani, A.; Cinque, P.; de Luca, A.; Di Biagio, A.; Gori, A.; Guaraldi, G.; Lapadula, G.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Puoti, M.; Quiros Roldan, E.; Cicconi, P.; Formenti, T.; Galli, L.; Lorenzini, P.; Giacometti, A.; Costantini, A.; Santoro, C.; Suardi, C.; Viale, P.; Vanino, E.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Cassola, G.; Viscoli, G.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Puzzolante, C.; Abrescia, N.; Guida, M. G.; Onofrio, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; d'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Pellizzer, G.; Manfrin, V.; Caissotti, C.; Dellamonica, P.; Bernard, E.; Cua, E.; de Salvador-Guillouet, F.; Durant, J.; Ferrando, S.; Mondain-Miton, V.; Naqvi, A.; Perbost, I.; Prouvost-Keller, B.; Pillet, S.; Pugliese, P.; Rahelinirina, V.; Roger, P. M.; Dollet, K.; Aubert, V.; Barth, J.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton-Jeangros, C.; Calmy, A.; Egger, M.; Fehr, J.; Fellay, J.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, A.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Yerly, S.

    2015-01-01

    The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. Participants were followed from the latest of D:A:D study entry or January 1, 2004,

  7. Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy : the D: A: D study

    NARCIS (Netherlands)

    Bruyand, Mathias; Ryom, Lene; Shepherd, Leah; Fatkenheuer, Gerd; Grulich, Andrew; Reiss, Peter; de Wit, Stéphane; D Arminio Monforte, Antonella; Furrer, Hansjakob; Pradier, Christian; Lundgren, Jens; Sabin, Caroline; Schölvinck, Elisabeth H.

    2015-01-01

    BACKGROUND: The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS: Participants were followed from the latest of D:A:D study entry or

  8. Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study

    NARCIS (Netherlands)

    Bruyand, M.; Ryom, L.; Shepherd, L.; Fatkenheuer, G.; Grulich, A.; Reiss, P.; Wit, S. de; Monforte, A.M.; Furrer, H.; Pradier, C.; Lundgren, J.; Sabin, C.; Warris, A.

    2015-01-01

    BACKGROUND: The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS: Participants were followed from the latest of D:A:D study entry or

  9. Efficiently Combining Water Reuse and Desalination through Forward Osmosis—Reverse Osmosis (FO-RO Hybrids: A Critical Review

    Directory of Open Access Journals (Sweden)

    Gaetan Blandin

    2016-07-01

    Full Text Available Forward osmosis (FO is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application and water management challenges (proximity of wastewater and desalination plants, FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full-scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling.

  10. Efficiently Combining Water Reuse and Desalination through Forward Osmosis—Reverse Osmosis (FO-RO) Hybrids: A Critical Review

    Science.gov (United States)

    Blandin, Gaetan; Verliefde, Arne R.D.; Comas, Joaquim; Rodriguez-Roda, Ignasi; Le-Clech, Pierre

    2016-01-01

    Forward osmosis (FO) is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO) hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application) and water management challenges (proximity of wastewater and desalination plants), FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO) demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs) in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full-scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling. PMID:27376337

  11. Efficiently Combining Water Reuse and Desalination through Forward Osmosis-Reverse Osmosis (FO-RO) Hybrids: A Critical Review.

    Science.gov (United States)

    Blandin, Gaetan; Verliefde, Arne R D; Comas, Joaquim; Rodriguez-Roda, Ignasi; Le-Clech, Pierre

    2016-07-01

    Forward osmosis (FO) is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO) hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application) and water management challenges (proximity of wastewater and desalination plants), FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO) demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs) in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full-scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling.

  12. [Formation and Variation of Brominated Disinfection By-products in A Combined Ultrafiltration and Reverse Osmosis Process for Seawater Desalination].

    Science.gov (United States)

    Yang, Zhe; Sun, Ying-xue; Shi, Na; Hu, Hong-ying

    2015-10-01

    The characteristics of dissolved organic matter (DOM) and brominated disinfection by-products ( Br-DBPs ) during a seawater desalination ultrafiltration (UF) combined reverse osmosis (RO) process were studied. The seawater contained high level of bromide ion (45.6-50.9 mg x L(-1)) and aromatic compounds with specific ultraviolet absorbance ( SUVA) of 3.6-6.0 L x (mg x m)(-1). The tryptophan-like aromatic protein, fulvic acid-like and soluble microbial by-product-like were the main fluorescent DOM in the seawater. After pre-chlorination of the seawater, the concentrations of DBPs was significantly increased in the influent of UF, which was dominantly the Br-DBPs. Bromoform (CHBr3) accounted for 70.48% - 91.50% of total trihalomethanes (THMs), dibromoacetic acid (Br2CHCO2H) occupied 81.14% - 100% of total haloacetic acids (HAAs) and dibromoacetonitrile (C2HBr2N) occupied 83.77% - 87.45% of total haloacetonitriles ( HANs). The removal efficiency of THMs, HAAs and HANs by the UF membrane was 36.63% - 40.39%, 73.83% - 95.38% and 100%, respectively. The RO membrane could completely remove the HAAs, while a little of the THMs was penetrated. The antiestrogenic activity in the seawater was 0.35 - 0.44 mg x L(-1), which was increased 32% - 69% after the pre-chlorination. The DBPs and other bio-toxic organics which formed during the UF-RO process were finally concentrated in the UF concentrate and RO concentrate.

  13. The Ingenious Mr Hughes: Combining Forced, Fat, and Reverse Perspective All in One Art Piece to Pit Objects against Surfaces

    Directory of Open Access Journals (Sweden)

    Thomas V Papathomas

    2012-04-01

    Full Text Available The artist Patrick Hughes has ingeniously painted rows of stacked Brillo boxes in Forced into Reverse Perspective. The geometry is in reverse perspective, predicting only one type of illusory motion for each planar surface for moving viewers. He “broke” these surfaces into objects by painting the boxes in three types of perspective (planar, forced, and reverse. Our experiments confirmed that he succeeded in eliciting different types of illusory motion, including “differential motion” between boxes for most viewers. In some sense, this illustrates the superiority of secondary (painted over primary (physical cues.

  14. Effect of lauric arginate, nisin Z, and a combination against several food-related bacteria.

    Science.gov (United States)

    Pattanayaiying, Rinrada; H-Kittikun, Aran; Cutter, Catherine N

    2014-10-01

    The effects of lauric arginate (LAE) and nisin Z, alone or in combination, on cell damage were investigated against Escherichia coli O157:H7, Listeria monocytogenes and Brochothrix thermosphacta, by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations, efflux of potassium and phosphate ions, and growth inhibition. A combination of LAE with nisin Z caused severe and dramatic changes in the cytoplasmic membrane and cell lysis of both Gram-positive and Gram-negative bacteria. The combination treatment also caused significant potassium and phosphate ion leakage of E. coli O157:H7, L. monocytogenes and B. thermosphacta, when compared with other treatments: 16.62±1.05, 50.35±0.81 and 45.47±1.15mg/L of potassium ion and 122.66±8.81, 97.96±3.31 and 26.47±13.97mg/L of phosphate ion after treatment for 6h, respectively. Bacteria were reduced by approximately 7log10CFU/mL within the first hour of treatment and then cells were unable to grow for the remainder of the experiment. Treatment with LAE alone resulted in changes in cellular morphology, coagulation of the cytoplasm, and low level leakage of potassium and phosphate ions in all bacteria tested. Treatment of L. monocytogenes and B. thermosphacta with nisin Z (320AU/mL of final concentration) resulted in the formation of membrane channels and leakage of potassium and phosphate ions at rather high levels; but the bacteriocin was not effective against E. coli O157:H7. LAE or nisin Z reduced growth of both L. monocytogenes and B. thermosphacta by approximately 7log10CFU/mL. Conversely, E. coli O157:H7 was not inhibited by treatments with nisin Z, but decreased by approximately 4.45log10CFU/mL after treatment with LAE. These findings provide additional information on the mode of action of these compounds on bacterial populations. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Visual detection of West Nile virus using reverse transcription loop-mediated isothermal amplification combined with a vertical flow visualization strip

    Directory of Open Access Journals (Sweden)

    Zengguo eCao

    2016-04-01

    Full Text Available West Nile virus (WNV causes a severe zoonosis, which can lead to a large number of casualties and considerable economic losses. A rapid and accurate identification methodfor WNV for use in field laboratories is urgently needed. Here, a method utilizing reverse transcription loop-mediated isothermal amplification combined with a vertical flow visualization strip (RT-LAMP-VF was developed to detect the envelope (E gene of WNV. The RT-LAMP-VF assay could detect 102 copies/μl ofan WNV RNA standard using a 40 min amplification reaction followed by a 2 min incubationof the amplification product on the visualization strip, and no cross-reaction with other closely related members of theFlavivirus genus was observed. The assay was further evaluated using cells and mouse brain tissues infected with a recombinant rabies virus expressing the E protein of WNV.The assay produced sensitivities of 101.5TCID50/ml and 101.33 TCID50/ml for detection of the recombinant virus in the cells and brain tissues, respectively. Overall, the RT-LAMP-VF assay developed in this study is rapid, simple and effective, and it is therefore suitable for clinical application in the field.

  16. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang

    2015-09-01

    Full Text Available Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID. JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK cells with normal numbers of poorly functioning B cells (T–B+NK–. Using SCID patient-specific induced pluripotent stem cells (iPSCs and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  17. Combining Transcranial Magnetic Stimulation and Electroencephalography May Contribute to Assess the Severity of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Petro Julkunen

    2011-01-01

    Full Text Available Alzheimer's disease (AD is the most common form of old age dementia, and mild cognitive impairment (MCI often precedes AD. In our previous study (Julkunen et al. 2008, we found that the combination of transcranial magnetic stimulation (TMS and electroencephalography (EEG was able to find distinct differences in AD and MCI patients as compared to controls. Here, we reanalyzed the small sample data from our previous study with the aim to test the sensitivity of the TMS-EEG characteristics to discriminate control subjects (n=4 from MCI (n=5 and AD (n=5 subjects. Furthermore, we investigated how the TMS-EEG response characteristics related to the scores of the dementia rating scales used to evaluate the severity of cognitive decline in these subjects. We found that the TMS-EEG response P30 amplitude correlated with cognitive decline and showed good specificity and sensitivity in identifying healthy subjects from those with MCI or AD. Given the small sample size, further studies may be needed to confirm the results.

  18. Therapy of Severe Heatshock in Combination With Multiple Organ Dysfunction With Continuous Renal Replacement Therapy

    Science.gov (United States)

    Chen, Guang-Ming; Chen, Yang-Hong; Zhang, Wei; Yu, Yi; Chen, Jin-Hua; Chen, Jian

    2015-01-01

    Abstract This study aimed to compare the clinical effects of continuous renal replacement therapy (CRRT) and routine therapy in heatshock (HS) patients. We retrospectively reviewed the clinical information of 33 severe exertional HS patients who were treated from February 1998 to October 2013. On the basis of whether or not CRRT therapy was used in addition to conventional therapy, patients were divided into a CRRT group (n = 15) and a control group (n = 18). Body temperature, blood gas analysis, routine blood tests, blood eletrolytes, enzymes and kidney function data, and APACHE II scores were obtained and compared between the 2 groups on admission and 3, 5, and 7 days after admission. Mortality was also compared between the 2 groups. CRRT treatment combined with conventional treatment resulted in a higher hospital-discharge rate, a faster return to normal of body temperature, greater increase in platelets, a greater decrease in WBC, neutrophils, and serum markers for liver and kidney dysfunction, greater improvement of organ dysfunction, and lower APACHE II scores than conventional treatment used alone. The addition of CRRT to conventional treatment for HS improves survival and causes a faster return to normal of serum markers and organ function. PMID:26252279

  19. Refinement of linkage of human severe combined immunodeficiency (SCIDXI) to polymorphic markers in Xq13

    Energy Technology Data Exchange (ETDEWEB)

    Puck, J.M (Children' s Hospital of Philadelphia, PA (United States) Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)); Conely, M.E. (St. Jude Children' s Research Hospital and Univ. of Tennessee School of Medicine, Memphis (United States)); Bailey, L.C. (Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States))

    1993-07-01

    The most common form of human severe combined immunodeficiency (SCID) is inherited as an X-linked recessive genetic defect, MIM 300400. The disease locus, SCIDX1, has previously been placed in Xq13.1-q21.1 by demonstration of linkage to polymorphic markers between DXS159 and DXS3 and by exclusion from interstitial deletions of Xq21.1-q21.3. The authors report an extension of previous linkage studies, with new markers and a total of 25 SCIDX1 families including female carriers identified by nonrandom X chromosome inactivation in their T lymphocytes. SCIDX1 was nonrecombinant with DXS441, with a lod score of 17.96. Linkage relationships of new markers in the SCIDX1 families were consistent with the linkage map generated in the families of the Centre d'Etude du Polymorphisms Humain (CEPH) and with available physical map data. The most likely locus order was DXS1-(DXS159,DXS153)-DXS106-DXS132-DXS453-(SCIDX1,PGK1, DXS325,DXS347,DXS441)-DXS447-DXS72-DXYS1X-DXS3. The SCIDX1 region now spans approximately 10 Mb of DNA in Xq13; this narrowed genetic localization will assist efforts to identify gene candidates and will improve genetic management for families with SCID. 25 refs., 3 figs., 2 tabs.

  20. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Directory of Open Access Journals (Sweden)

    Satoshi Horino

    Full Text Available X-linked severe combined immunodeficiency (SCID-X1 is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc gene, and characterized by a complete defect of T and natural killer (NK cells. Gene therapy for SCID-X1 using conventional retroviral (RV vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  1. Newborn Screening for Severe Combined Immunodeficiency-A History of the TREC Assay

    Directory of Open Access Journals (Sweden)

    Mary T. Bausch-Jurken

    2017-06-01

    Full Text Available Infants born with T cell lymphopenias, especially severe combined immunodeficiency (SCID are at risk for serious, often fatal infections without intervention within the first year or two of life. The majority of these disorders can be detected through the use of the T cell recombination excision circle assay (TREC assay. The TREC assay detects the presence of non-replicating, episomal DNA that is formed during T cell development. This assay initially developed to measure thymic output during aging and HIV infection, has undergone modifications for the purpose of newborn screening (NBS for SCID. To meet the requirements for inclusion on NBS panels, the assay needed to utilize blood from dried blood spots on NBS cards, and be both sensitive and specific, avoiding the costs of false positives. Currently, the assay relies upon real time, quantitative PCR (RT-qPCR to detect TRECs in punches taken from dried blood spots. This review seeks to highlight some of the early work leading up to the initial implementation of the TREC assay for SCID detection, and the subsequent revisions made to optimize the assay.

  2. Severe muscle atrophy due to spinal cord injury can be reversed in complete absence of peripheral nerves

    Directory of Open Access Journals (Sweden)

    Simona Boncompagni

    2012-12-01

    Full Text Available In the last years, a new efficient treatment has been developed to treat paralyzed skeletal muscle of patients affected by spinal cord injury (SCI. The capability of the functional electrical stimulation (FES to improve trophism and in some cases muscle function, are now well documented both in animals after experimental cord lesion, and in humans, generally after traumatic cord lesion. This new findings makes FES an important tool for the rehabilitation of SCI patients. FES stimulation has been proven to be an effective method used to retard muscle atrophy and improve recovery after reinnervation. Sophisticated FES devices have been developed for restoring function in the upper and lower extremities, the bladder and bowel, and the respiratory system of SCI patients. However, there are SCI cases, such as those affected by flaccid paralysis, in which the musculature is not treated with FES rehabilitation therapy. This is because conventional FES apparatuses are designed for direct stimulation of peripheral nerves that need small currents to be depolarized, and are not effective in patients that have lost their peripheral nerves, and, therefore, require higher currents for the direct depolarization of the muscle fibers. Lack of muscle treatment generates, as a secondary problem, a long series of alterations to tissues other than muscle, such as bones (osteoporosis, skin (pressure sores, decubital ulcers, etc., that are a direct consequence of inactivity and poor blood supply to the denervated areas. These complications represent an extremely serious problem for the general health of the injured individuals, who usually have a shorter than normal life span. In the hopes of changing this common belief, an innovative rehabilitation procedure, based on FES, has been developed with the aim of reversing long-lasting muscle atrophy in the muscles of the lower extremities of SCI patients affected by complete lesion of the conus cauda, i.e. that have no

  3. Severe reversible dilated cardiomyopathy associated with a large left ventricular thrombus in a young child with middle aortic syndrome

    OpenAIRE

    Ponniah, U; Overholt, E

    2014-01-01

    this article reports a case of a seven-year girl who presented with severe dilated cardiomyopathy (DCM) associated with a large thrombus in the left ventricle (LV). She had a long segment stenosis of the lower thoracic descending aorta, possibly due to non-specific aortitis and underwent successful stent angioplasty. The LV thrombus resolved after heparin without sequelae.

  4. Severe reversible dilated cardiomyopathy associated with a large left ventricular thrombus in a young child with middle aortic syndrome.

    Science.gov (United States)

    Ponniah, U; Overholt, E

    2014-01-01

    We report a case of a seven-year girl who presented with severe dilated cardiomyopathy (DCM) associated with a large thrombus in the left ventricle (LV). She had a long segment stenosis of the lower thoracic descending aorta, possibly due to non-specific aortitis and underwent successful stent angioplasty. The LV thrombus resolved after heparin without sequelae.

  5. Mandibular distraction combined with orthognathic techniques for the correction of severe adult mandibular hypoplasia.

    Science.gov (United States)

    Yin, Lin; Tang, Xiaojun; Shi, Lei; Yin, Hongyu; Zhang, Zhiyong

    2014-11-01

    Mandibular hypoplasia may result from congenital deformities or trauma or infection during the early stage of facial skeleton development. Deficiencies in the growth of the mandible can not only cause various degrees of facial deformity but also affect breathing and occlusal function. Here, we report our experiences with mandibular distraction combined with orthognathic surgical techniques for the treatment of severe adult mandibular hypoplasia. Cephalometric analysis was conducted in all patients for quantitative evaluation. A computer-assisted surgical simulation was prepared before distraction. According to the simulation data, an operative osteotomy guide plate was designed and three-dimensionally printed with photosensitive resin. With the help of the guide plate, the osteotomy line was precisely placed. An internal distractor was then placed through an extraoral incision created under general anesthesia. Distraction began after 7 days of latency at the rate of 1 mm/d. After a 6- to 8-month consolidation period, the distractor was removed. At the same time, genioplasty and/or subapical osteotomy was performed to correct the patient's crossbite and improve the facial contour for bilateral mandibular hypoplasia. For unilateral mandibular hypoplasia, a Le Fort I osteotomy was performed to correct the open bite on the affected side, whereas a mandibular outer cortex excision was performed on the unaffected side to improve lower facial symmetry. The mandible symmetry and chin protrusion were efficiently improved in all 36 patients (mean age, 20.3 y). No facial nerve palsy was reported, nor were there complaints about postoperative facial scarring. The postoperative infection rate was 2.8%. The distance of lengthening was 26.2 (2.8) mm. The increased ramus length on the affected side was 18.9 (9.3) mm. At the end of the consolidation period (T2), the affected mandibular ramus length increased by 46.3% (23.6%) in unilateral distraction osteogenesis; however, it

  6. Reversible immobilization of free-ranging snow leopards (panthera uncia) with a combination of medetomidine and tiletamine-zolazepam.

    Science.gov (United States)

    Johansson, Örjan; Malmsten, Jonas; Mishra, Charudutt; Lkhagvajav, Purevjav; McCarthy, Tom

    2013-04-01

    Conservation and research of the elusive snow leopard (Panthera uncia) have been hampered by inadequate knowledge about its basic life history. Global positioning system (GPS) collars can provide useful information, but there has been limited information available on safe capture methods, drug doses, and efficacy for effective immobilization of free-ranging snow leopards. We describe a drug protocol using a combination of medetomidine and tiletamine-zolazepam for the chemical immobilization of free-ranging snow leopards. We also describe physiologic responses to immobilization drugs, including rectal temperature, heart rate, respiratory rate, and relative hemoglobin oxygen saturation (SpO2) recorded every 10 min. Our study was carried out in the Tost Mountains adjacent to the Great Gobi Desert, in southern Mongolia, between August 2008 and April 2012. Eighteen snow leopards were captured or recaptured with foot-snares on 42 occasions and anesthetized for marking with GPS collars. The snow leopards received on average (±SD) 0.020±0.04 mg/kg body mass medetomidine and 2.17±0.45 mg/kg tiletamine-zolazepam. The duration of ensuing anesthesia was 69±13 min, including an induction period of 10 (±4) min. Anesthesia was reversed with 4 mg (0.10±0.04 mg/kg) atipamezole administered intramuscularly. The mean value for SpO2 for the 37 captures where we could record physiologic values was 91±4. The SpO2 increased significantly during anesthesia (+0.06±0.02%/min), whereas rectal temperature (average 38.1±0.7 C/min, change -0.04±0.003 C/min), heart rate (average 97±9 beats/min, change -0.20±0.03 beats/min), and respiratory rate (average 26±6 breaths/min, change -0.11±0.03 breaths/min) decreased significantly. A dose of 80 mg tiletamine-zolazepam (2 mg/kg body weight) and 0.72 mg medetomidine (0.02 mg/kg body weight) safely immobilized all adult and subadult snow leopards (weight 25-45 kg) in our study. All measured physiologic values remained within clinically

  7. First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency—Clinical Achievements and Insights

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    Erez Rechavi

    2017-11-01

    Full Text Available Severe combined immunodeficiency (SCID, the most severe form of T cell immunodeficiency, is detectable through quantification of T cell receptor excision circles (TRECs in dried blood spots obtained at birth. Herein, we describe the results of the first year of the Israeli SCID newborn screening (NBS program. This important, life-saving screening test is available at no cost for every newborn in Israel. Eight SCID patients were diagnosed through the NBS program in its first year, revealing an incidence of 1:22,500 births in the Israeli population. Consanguine marriages and Muslim ethnic origin were found to be a risk factor in affected newborns, and a founder effect was detected for both IL7Rα and DCLRE1C deficiency SCID. Lymphocyte subset analysis and TREC quantification in the peripheral blood appear to be sufficient for confirmation of typical and leaky SCID and ruling out false positive (FP results. Detection of secondary targets (infants with non-SCID lymphopenia did not significantly affect the management or outcomes of these infants in our cohort. In the general, non-immunodeficient population, TREC rises along with gestational age and birth weight, and is significantly higher in females and the firstborn of twin pairs. Low TREC correlates with both gestational age and birth weight in extremely premature newborns. Additionally, the rate of TREC increase per week consistently accelerates with gestational age. Together, these findings mandate a lower cutoff or a more lenient screening algorithm for extremely premature infants, in order to reduce the high rate of FPs within this group. A significant surge in TREC values was observed between 28 and 30 weeks of gestation, where median TREC copy numbers rise by 50% over 2 weeks. These findings suggest a maturational step in T cell development around week 29 gestation, and imply moderate to late preterms should be screened with the same cutoff as term infants. The SCID NBS program is still

  8. Granulocyte transfusion combined with granulocyte colony stimulating factor in severe infection patients with severe aplastic anemia: a single center experience from China.

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    Huaquan Wang

    Full Text Available OBJECTIVE: To investigate the efficacy and safety of granulocyte transfusion combined with granulocyte colony stimulating factor (G-CSF in severe infection patients with severe aplastic anemia (SAA. METHODS: Fifty-six patients in severe infections with SAA who had received granulocyte transfusions combined with G-CSF from 2006 to 2012 in our department were analyzed. A retrospective analysis was undertaken to investigate the survival rates (at 30 days, 90 days and 180 days, the responses to treatment (at 7 days and 30 days, including microbiological, radiographic and clinical responses, the neutrophil count and adverse events after transfusion. RESULTS: All SAA patients with severe infections were treated with granulocyte transfusions combined with G-CSF. Forty-seven patients had received antithymocyte globulin/antilymphocyte globulin and cyclosporine A as immunosuppressive therapy. The median number of granulocyte components transfused was 18 (range, 3-75. The survival at 30 days, 90 days and 180 days were 50(89%, 39(70% and 37(66% respectively. Among 31 patients who had invasive fungal infections, the survival at 30 days, 90 days and 180 days were 27(87%, 18(58% and 16(52% respectively. Among the 25 patients who had refractory severe bacterial infections, the survival at 30 days, 90 days and 180 days were 23(92%, 21(84% and 21(84% respectively. Survival rate was correlated with hematopoietic recovery. Responses of patients at 7 and 30 days were correlated with survival rate. Common adverse effects of granulocyte transfusion included mild to moderate fever, chills, allergy and dyspnea. CONCLUSION: Granulocyte transfusions combined with G-CSF could be an adjunctive therapy for treating severe infections of patients with SAA.

  9. A Markov model to analyze cost-effectiveness of screening for severe combined immunodeficiency (SCID).

    Science.gov (United States)

    Chan, Kee; Davis, Joie; Pai, Sung-Yun; Bonilla, Francisco A; Puck, Jennifer M; Apkon, Michael

    2011-11-01

    To evaluate the cost-effectiveness of universal neonatal screening for T cell lymphocytopenia in enhancing quality of life and life expectancy for children with severe combined immunodeficiency (SCID). Decision trees were created and analyzed to estimate the cost, life years, and quality adjusted life years (QALYs) across a population when universal screening for lack of T cells is used to detect SCID, as implemented in five states, compared to detection based on recognizing symptoms and signs of disease. Terminal values of each tree limb were derived through Markov models simulating the natural history of three cohorts: unaffected subjects; those diagnosed with SCID as neonates (early diagnosis); and those diagnosed after becoming symptomatic and arousing clinical suspicion (late diagnosis). Models considered the costs of screening and of care including hematopoietic cell transplantation for affected individuals. Key decision variables were derived from the literature and from a survey of families with children affected by SCID, which was used to describe the clinical history and healthcare utilization for affected subjects. Sensitivity analyses were conducted to explore the influence of these decision variables. Over a 70-year time horizon, the average cost per infant was $8.89 without screening and $14.33 with universal screening. The model predicted that universal screening in the U.S. would cost approximately $22.4 million/year with a gain of 880 life years and 802 QALYs. Sensitivity analyses showed that screening test specificity and disease incidence were critical driving forces affecting the incremental cost-effectiveness ratio (ICER). Assuming a SCID incidence of 1/75,000 births and test specificity and sensitivity each at 0.99, screening remained cost-effective up to a maximum cost of $15 per infant screened. At our current estimated screening cost of $4.22/infant, universal screening for SCID would be a cost effective means to improve quality and

  10. Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases

    Directory of Open Access Journals (Sweden)

    O. Jilkina

    2014-01-01

    Full Text Available In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70 deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ deficiency. As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID patients were studied: 1 T-negative PID (cartilage-hair hypoplasia and 4 T-positive PID (2 common immune deficiency (CID, 1 Wiskott–Aldrich syndrome, and 1 X-linked lymphoproliferative disease. Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982 were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.

  11. Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases.

    Science.gov (United States)

    Jilkina, O; Thompson, J R; Kwan, L; Van Caeseele, P; Rockman-Greenberg, C; Schroeder, M L

    2014-01-01

    In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID) is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC) assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified) and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70) deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ) deficiency). As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID) patients were studied: 1 T-negative PID (cartilage-hair hypoplasia) and 4 T-positive PID (2 common immune deficiency (CID), 1 Wiskott-Aldrich syndrome, and 1 X-linked lymphoproliferative disease). Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982) were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.

  12. Sensory Neuronopathy Revealing Severe Vitamin B12 Deficiency in a Patient with Anorexia Nervosa: An Often-Forgotten Reversible Cause.

    Science.gov (United States)

    Franques, Jérôme; Chiche, Laurent; Mathis, Stéphane

    2017-03-15

    Vitamin B12 (B12) deficiency is known to be associated with various neurological manifestations. Although central manifestations such as dementia or subacute combined degeneration are the most classic, neurological manifestations also include sensory neuropathies. However, B12 deficiency is still rarely integrated as a potential cause of sensory neuronopathy. Moreover, as many medical conditions can falsely normalize serum B12 levels even in the context of a real B12 deficiency, some cases may easily remain underdiagnosed. We report the illustrating case of an anorexic patient with sensory neuronopathy and consistently normal serum B12 levels. After all classical causes of sensory neuronopathy were ruled out, her clinical and electrophysiological conditions first worsened after folate administration, but finally improved dramatically after B12 administration. B12 deficiency should be systematically part of the etiologic workup of sensory neuronopathy, especially in a high risk context such as anorexia nervosa.

  13. Persistent downregulation of calcium-sensing receptor mRNA in rat parathyroids when severe secondary hyperparathyroidism is reversed by an isogenic kidney transplantation.

    Science.gov (United States)

    Lewin, Ewa; Garfia, Bartolome; Recio, Fernando Luque; Rodriguez, Mariano; Olgaard, Klaus

    2002-08-01

    Experimental severe secondary hyperparathyroidism (HPT) is reversed within 1 wk after reversal of uremia by an isogenic kidney transplantation (KT) in the uremic rats. Abnormal parathyroid hormone (PTH) secretion in uremia is related to downregulation of CaR and vitamin D receptor (VDR) in the parathyroid glands (PG). The aim of this investigation was to examine the expression of CaR and VDR genes after reversal of uremia and HPT in KT rats. 5/6 nephrectomized rats were kept on a normal or high-phosphorus (hP) diet for 8 wk to induce severe HPT (n = 8 in each group). In another group of seven uremic hP rats, uremia was reversed by an isogenic KT and PG were harvested within 1 wk posttransplant. Plasma urea, creatinine, total calcium, phosphorus, and PTH levels were measured. Parathyroid CaR and VDR mRNA were measured by quantitative PCR. Uremic hP rats had significantly elevated levels of creatinine, urea, and phosphorus (P rats. After KT, the levels were normalized from day 3 to 7: creatinine from 0.117 +/- 0.016 to 0.050 +/- 0.002 mmol/L; urea from 23 +/- 4 to 7 +/- 0.3 mmol/L; phosphorus from 3.9 +/- 0.6 to 1.5 +/- 0.06 mmol/L; calcium from 1.8 +/- 0.2 to 2.5 +/- 0.02 mmol/L. Plasma PTH levels fell from 849 +/- 224 to a normal level of 38 +/- 9 pg/ml (P rats on a standard diet, CaR mRNA was similar to that of normal control rats, whereas VDR mRNA was significantly decreased. In uremic rats kept on hP diet, CaR mRNA was significantly decreased to 26 +/- 7% of control rats (P = 0.01) and VDR mRNA reduced to 36 +/- 11% (P rats, both CaR mRNA and VDR mRNA remained severely reduced (CaR, 39 +/- 7%; VDR, 9 +/- 3%; P rats. In conclusion, circulating plasma PTH levels normalized rapidly after KT, despite persisting downregulation of CaR and VDR gene expression. This indicates that upregulation of CaR mRNA and VDR mRNA is not necessary to induce the rapid normalization of PTH secretion from hyperplastic parathyroid glands.

  14. Reversal of echocardiographic right-sided heart pathology in a dog with severe pulmonary hypertension: a case report

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    McMahon P

    2015-06-01

    Full Text Available Peggy McMahon,1 Carley Saelinger 2  1Emergency and Critical Care Department, 2Cardiology Department, Animal Specialty and Emergency Center, Los Angeles, CA, USA Abstract: Pathologic right-sided heart changes are a common echocardiographic finding in patients with pulmonary hypertension (PH. Canines with PH may have right heart pathology documented via echocardiographic color Doppler interrogation including tricuspid valve regurgitation, pulmonic valve insufficiency, elevated pulmonary arterial systolic pressure, elevated pulmonary arterial diastolic pressure, and alterations in ejection profiles. Two-dimensional echocardiographic findings may include right ventricular hypertrophy, interventricular septal flattening, paradoxical interventricular septal motion, pulmonary artery dilation, and potentially abnormal left heart dimensions. In veterinary medicine, much confidence is given to the measurement of pulmonary arterial systolic pressure estimated from tricuspid valve regurgitation to grade the severity of PH and monitor its improvement with little emphasis placed on the integration of two-dimensional echocardiographic right and left heart pathology in conjunction with Doppler findings. To the authors’ knowledge, marked improvement and/or resolution of echocardiographic-documented right heart pathology have not been previously reported in the veterinary literature. This case report documents profound echocardiographic improvement of right-sided heart disease in a dog with severe PH. Keywords: canine, pulmonary hypertension, tricuspid valve regurgitation, right heart hypertrophy, sildenafil  

  15. Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering"

    OpenAIRE

    Liu, M.; Bienfait, B.; Sacher, O.; Gasteiger, J.; Siezen, R.J.; Nauta, A.; Geurts, J.M.

    2014-01-01

    The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bio...

  16. Major role for amphotericin B-flucytosine combination in severe cryptococcosis.

    Directory of Open Access Journals (Sweden)

    Françoise Dromer

    Full Text Available BACKGROUND: The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals. METHODOLOGY/PRINCIPAL FINDINGS: Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2 and 3 months (Mo3 after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001. In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21-16.23], p = 0.025 and abnormal brain imaging (OR = 3.89[1.23-12.31], p = 0.021 at baseline. Haematological malignancy (OR = 4.02[1.32-12.25], p = 0.015, abnormal neurology at baseline (OR = 2.71[1.10-6.69], p = 0.030 and prescription of 5FC for less than 14 days (OR = 3.30[1.12-9.70], p = 0.030 were independently associated with treatment failure at Mo3. CONCLUSION/SIGNIFICANCE: Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and

  17. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States.

    Science.gov (United States)

    Kwan, Antonia; Abraham, Roshini S; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E; Bonilla, Francisco A; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A; Comeau, Anne Marie; Connelly, James A; Cowan, Morton J; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W; Hale, Jaime E; Hanson, I Celine; Hay, Beverly N; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M; Kohn, Donald B; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B; Naides, Stanley J; Notarangelo, Luigi D; Orange, Jordan S; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A; Scott, Ginger; Scott, Patricia M; Secord, Elizabeth; Seroogy, Christine; Shearer, William T; Siegel, Subhadra; Silvers, Stacy K; Stiehm, E Richard; Sugerman, Robert W; Sullivan, John L; Tanksley, Susan; Tierce, Millard L; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E; Wasserman, Richard L; Watson, Michael S; Weinberg, Geoffrey A; Weiner, Leonard B; Wood, Heather; Yates, Anne B; Puck, Jennifer M; Bonagura, Vincent R

    2014-08-20

    Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. Epidemiological and retrospective observational study. Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection

  18. Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

    Science.gov (United States)

    Kwan, Antonia; Abraham, Roshini S.; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K.; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E.; Bonagura, Vincent R.; Bonilla, Francisco A.; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A.; Comeau, Anne Marie; Connelly, James A.; Cowan, Morton J.; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T.; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W.; Hale, Jaime E.; Celine Hanson, I.; Hay, Beverly N.; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M.; Kohn, Donald B.; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B.; Naides, Stanley J.; Notarangelo, Luigi D.; Orange, Jordan S.; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A.; Scott, Ginger; Scott, Patricia M.; Secord, Elizabeth; Seroogy, Christine; Shearer, William T.; Siegel, Subhadra; Silvers, Stacy K.; Stiehm, E. Richard; Sugerman, Robert W.; Sullivan, John L.; Tanksley, Susan; Tierce, Millard L.; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E.; Wasserman, Richard L.; Watson, Michael S.; Weinberg, Geoffrey A.; Weiner, Leonard B.; Wood, Heather; Yates, Anne B.; Puck, Jennifer M.

    2015-01-01

    IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in

  19. Case report: fast reversal of severe osteoporosis after correction of excessive levothyroxine treatment and long-term follow-up.

    Science.gov (United States)

    Laine, C M; Landin-Wilhelmsen, K

    2017-07-01

    This case report describes a 38-year-old woman, who presented with bilateral femoral stress fractures and osteoporosis after years of excessive levothyroxine treatment. Her bone health was restored rapidly and long-lasting with the reduction of levothyroxine dosage. No bone-active treatment was warranted. Hyperthyroidism is a known risk factor for osteoporosis and fractures. Recent studies on patients with serum thyrotropin-suppressive therapy have not, however, indicated adverse effects on bone during long-term follow-up. This case report describes long-term follow-up data of a clinically euthyreoid patient, who developed symptomatic osteoporosis due to excessive levothyroxine treatment. After correction of levothyroxine dosage, her bone mineral density (BMD) and previously elevated serum osteocalcin levels normalized rapidly and she remained free from fractures during 23 years of follow-up over menopause. Excessive TSH suppression contributed to the secondary osteoporosis in this patient; BMD normalized after dose reduction of levothyroxine and no fractures occurred during 23 years' follow-up. Some patients develop severe osteoporosis if they are over-substituted with levothyroxine, and decent follow-up of patients with levothyroxine supplementation is mandatory.

  20. Combined multivariate and pathway analyses show that allergen-induced gene expression changes in CD4+ T cells are reversed by glucocorticoids.

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    Yelin Zhao

    Full Text Available BACKGROUND: Glucocorticoids (GCs play a key role in the treatment of allergy. However, the genome-wide effects of GCs on gene expression in allergen-challenged CD4(+ T cells have not been described. The aim of this study was to perform a genome-wide analysis to investigate whether allergen-induced gene expression changes in CD4(+ T cells could be reversed by GCs. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression microarray analysis was performed to profile gene expression in diluent- (D, allergen- (A, and allergen + hydrocortisone- (T challenged CD4(+ T cells from patients with seasonal allergic rhinitis. Principal component analysis (PCA showed good separation of the three groups. To identify the correlation between changes in gene expression in allergen-challenged CD4(+ T cells before and after GC treatment, we performed orthogonal partial least squares discriminant analysis (OPLS-DA followed by Pearson correlation analysis. This revealed that allergen-induced genes were widely reversed by GC treatment (r = -0.77, P<0.0001. We extracted 547 genes reversed by GC treatment from OPLS-DA models based on their high contribution to the discrimination and found that those genes belonged to several different inflammatory pathways including TNFR2 Signalling, Interferon Signalling, Glucocorticoid Receptor Signalling and T Helper Cell Differentiation. The results were supported by gene expression microarray analyses of two independent materials. CONCLUSIONS/SIGNIFICANCE: Allergen-induced gene expression changes in CD4(+ T cells were reversed by treatment with glucocorticoids. The top allergen-induced genes that reversed by GC treatment belonged to several inflammatory pathways and genes of known or potential relevance for allergy.

  1. A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension.

    Science.gov (United States)

    Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran

    2016-04-01

    A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances.

  2. STUDY OF SYMPTOMS AND SIGNS RELATED TO CARDIO-VASCULAR SYSTEM, ESPECIALLY CARDIAC MURMURS IN SEVERE ANAEMIA AND ITS REVERSIBILITY AFTER CORRECTION OF ANAEMIA

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    Manjiri Pramod Dhamangaonkar

    2017-09-01

    Full Text Available BACKGROUND Anaemia is one of the commonest clinical problems in our country. It affects various organs including heart. Clinical manifestations of anaemia referable to cardiovascular system may closely simulate symptoms and signs of organic heart disease, especially cardiac murmurs. The cardiac murmurs show either improvement or disappearance after correction of anaemia. The aim of this study was to evaluate various clinical changes (symptoms and signs related to cardiovascular system in patients of severe anaemia and their reversibility after treatment of anaemia. MATERIALS AND METHODS 94 patients admitted in medicine wards in government general hospital, Solapur for severe anaemia (Hb concentration less than or equal to 7 gm% were studied. Symptoms, general examinations signs and systemic examination signs related to cardiovascular system were assessed on admission. All patients were treated with deworming, iron therapy (oral or parenteral or blood transfusion. All symptoms, general examination signs and systemic examination signs were reassessed after treatment. RESULTS 1 Majority symptoms and signs related to cardiovascular system, in patients of severe anaemia were found in females. 2 54 patients were having cardiac murmur, out of which 45 were females. 3 All symptoms and signs related to cardiovascular system were either improved or disappeared after treatment. CONCLUSION Patients with cardiac symptoms and or signs should be scrutinized for anaemia and treated accordingly especially females. Majority of these patients show disappearance of symptoms and signs after treatment.

  3. Combination of multistep IMAC enrichment with high-pH reverse phase separation for in-depth phosphoproteomic profiling.

    Science.gov (United States)

    Yue, Xiao-Shan; Hummon, Amanda B

    2013-09-06

    Typical mass spectrometric phosphoproteome studies are complicated by the need for large amounts of starting material and extensive sample preparation to ensure sufficient phosphopeptide identifications. In this paper, we present a novel strategy to perform optimized multistep IMAC enrichment from whole cell lysates followed by high-pH reverse phase fractionation (multi-IMAC-HLB; HLB means hydrophilic-lipophilic-balanced reversed-phase cartridge). The peptide-to-IMAC ratio was optimized to maximize IMAC performance, while multistep IMAC enrichment enabled improved phosphopeptide acquisition. The addition of the HLB step further fractionates the IMAC enriched phosphopeptides while desalting the samples, which dramatically reduces the sample manipulation time and sample loss compared to other popular strategies. We compared the phosphopeptide identification results of the multi-IMAC-HLB method with 3 mg of starting material to the well-established SCX-IMAC method with 15 mg of starting material. We identified 8969 unique phosphopeptides with the multi-IMAC-HLB method, compared to 5519 unique phosphopeptides identified with the SCX-IMAC method, an increase of 62.5%. The increase in the numbers of identified phosphopeptides is due to the increase in the ratio of identified phosphopeptides out of all detected peptides, 70.5% with multi-IMAC-HLB method compared to 32.3% with the SCX-IMAC method. Multi-IMAC-HLB is a robust and efficient method for in-depth phosphoproteomic research.

  4. Treatment of severe osteochondral defects of the knee by combined autologous bone grafting and autologous chondrocyte implantation using fibrin gel

    NARCIS (Netherlands)

    Konst, Y.E.; Benink, R.J.; Veldstra, R.; van der Krieke, T.J.; Helder, M.N.; van Royen, B.J.

    2012-01-01

    Purpose: Severe symptomatic and unstable osteochondral defects of the knee are difficult to treat. A variety of surgical techniques have been developed. However, the optimal surgical technique is still controversial. We present a novel technique in which autologous bone grafting is combined with

  5. Efficiencies of acid catalysts in the hydrolysis of lignocellulosic biomass over a range of combined severity factors

    Science.gov (United States)

    Jae-Won Lee; Thomas W. Jeffries

    2011-01-01

    Dicarboxylic organic acids have properties that differ from those of sulfuric acid during hydrolysis of lignocellulose. To investigate the effects of different acid catalysts on the hydrolysis and degradation of biomass compounds over a range of thermochemical pretreatments, maleic, oxalic and sulfuric acids were each used at the same combined severity factor (CSF)...

  6. Treatment Evaluation with Mometasone Furoate, Alone or in Combination with Desloratadine/ Montelukast in Moderate Severe Allergic Rhinitis

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    Florincescu-Gheorghe Nona-Aura

    2014-06-01

    Full Text Available Introduction: Allergic rhinitis is one of the most common allergic diseases, characterized by the inflammation of the nasal mucosa. Eosinophils play a predominant pro-inflammatory role in allergic inflammation. This study assesses the effect of mometasone furoate alone or in combination with desloratadine/montelukast in patients with moderate-severe allergic rhinitis.

  7. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene

    Science.gov (United States)

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor c...

  8. Trauma-focused treatment for posttraumatic stress disorder combined with CBT for severe substance use disorder: a randomized controlled trial

    NARCIS (Netherlands)

    van Dam, D.; Ehring, T.; Vedel, E.; Emmelkamp, P.M.G.

    2013-01-01

    Background: This randomized controlled trial (RCT) investigated the effectiveness of a combined treatment for co-morbid Posttraumatic Stress Disorder (PTSD) and severe Substance Use Disorder (SUD). Methods: Structured Writing Therapy for PTSD (SWT), an evidence-based traumafocused intervention, was

  9. The functional state of follicular dendritic cells in severe combined immunodeficient (SCID) mice: role of the lymphocytes

    NARCIS (Netherlands)

    Yoshida, K.; van den Berg, T. K.; Dijkstra, C. D.

    1994-01-01

    In the present study, we have investigated the capacity of follicular dendritic cells (FDC) to trap immune complexes (IC) in the splenic white pulp of severe combined immunodeficient (SCID) mice and the influence of lymphocyte transfer on FDC function. FDC are absent in the splenic white pulp of

  10. In vitro evaluation of antibiotics' combinations for empirical therapy of suspected methicillin resistant Staphylococcus aureus severe respiratory infections

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    Nicola Lucia

    2007-09-01

    Full Text Available Abstract Background Methicillin resistant Staphylococcus aureus (MRSA is an increasingly common cause of nosocomial infections, causing severe morbidity and mortality worldwide, and accounting in some hospitals for more than 50% of all S. aureus diseases. Treatment of infections caused by resistant bacterial pathogens mainly relies on two therapeutic modalities: development of new antimicrobials and use of combinations of available antibiotics. Combinations of antibiotics used in the empiric treatment of infections with suspected methicillin resistant Staphylococcus aureus etiology were investigated. Methods Double (vancomycin or teicoplanin with either levofloxacin or cefotaxime and triple (vancomycin or teicoplanin + levofloxacin + one among amikacin, ceftazidime, cefepime, imipenem, piperacillin/tazobactam combinations were evaluated by means of checkerboard assay and time kill curves. Mutational rates of single and combined drugs at antimicrobial concentrations equal to the resistance breakpoints were also calculated. Results Vancomycin or teicoplanin + levofloxacin showed synergy in 16/50 and in 9/50 strains respectively, while vancomycin or teicoplanin + cefotaxime resulted synergic for 43/50 and 23/50 strains, respectively. Triple combinations, involving teicoplanin, levofloxacin and ceftazidime or piperacillin/tazobactam gave synergy in 20/25 strains. Teicoplanin + levofloxacin gave synergy in triple combinations more frequently than vancomycin + levofloxacin. For single antibiotics, mutational frequencies ranged between 10-5 and -9 for levofloxacin, cefotaxime, amikacin and imipenem, and -9 for vancomycin and teicoplanin. When tested in combinations, mutational frequencies fell below 10-9 for all the combinations. Conclusion In vitro evidence of synergy between glycopeptides, fluoroquinolones (levofloxacin and β-lactams and of reduction of mutational frequencies by combinations are suggestive for a potential role in empirical therapy

  11. Clinical optical coherence tomography combined with multiphoton tomography for evaluation of several skin disorders

    Science.gov (United States)

    König, Karsten; Speicher, Marco; Bückle, Rainer; Reckfort, Julia; McKenzie, Gordon; Welzel, Julia; Koehler, Martin J.; Elsner, Peter; Kaatz, Martin

    2010-02-01

    The first clinical trial of optical coherence tomography (OCT) combined with multiphoton tomography (MPT) and dermoscopy is reported. State-of-the-art (i) OCT systems for dermatology (e.g. multibeam swept source OCT), (ii) the femtosecond laser multiphoton tomograph DermaInspectTM, and (iii) digital dermoscopes were applied to 47 patients with a diversity of skin diseases and disorders such as skin cancer, psoriasis, hemangioma, connective tissue diseases, pigmented lesions, and autoimmune bullous skin diseases. Dermoscopy, also called 'epiluminescent microscopy', provides two-dimensional color images of the skin surface. OCT imaging is based on the detection of optical reflections within the tissue measured interferometrically whereas nonlinear excitation of endogenous fluorophores and the second harmonic generation are the bases of MPT images. OCT cross sectional "wide field" image provides a typical field of view of 5 x 2 mm2 and offers fast information on the depth and the volume of the investigated lesion. In comparison, multiphoton tomography presents 0.36 x 0.36 mm2 horizontal or diagonal sections of the region of interest within seconds with submicron resolution and down to a tissue depth of 200 μm. The combination of OCT and MPT provides a synergistic optical imaging modality for early detection of skin cancer and other skin diseases.

  12. Objective Assessment of the Severity of Patients Suffering from Fall from Height with Combined Injuries of the Abdominal Parenchymal Organs

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    Abdukhakim Khadjibaev

    2015-06-01

    Full Text Available In recent years, fall from a height (FFH has been a relatively frequent cause of injury and death in the urban environment. The purpose of this study was to optimize the risk stratification of FFH victims with combined injuries of the abdominal organs by using Injury Severity Score (ISS scale. The study included 111 patients (aged between 15 and 80 years injured by FFH. All the falls were accidental and occurred mainly among males (82%. The height of the fall ranged from 2 to 5 meters. Combined injuries were found in 98 patients and isolated injuries in 13 patients. The combination of the 6 injured body regions was identified in 5 patients, 5 regions in 17, 4 in 35, 3 in 23, and 2 in 18. The abdomen trauma was most commonly associated with the following injured body regions: head and neck-chest-extremities and pelvis (13.3%, head and neck-chest-extremities (12.2%, and head and neck-chest-pelvis (9.2%. Among the combined injuries of the abdomen, ruptures of parenchymal organs (liver, spleen and kidneys were predominant. To assess the severity of the injury, the ISS scale was applied. The injuries of abdominal parenchymal organs were evaluated according to the AAST (American Association for the Surgery of Trauma classification. Comparative analysis of the assessment of the severity of a patient's condition according to the traditional scale and the ISS scale showed that the ISS scale promotes the active and timely detection of the extremely severe and terminal condition in patients with injuries due to FFH with combined trauma of the abdominal organs. Objective assessment of the severity of trauma and the dominant injury region allows determining the optimal treatment algorithm and predicting the outcome of the injury.

  13. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

    NARCIS (Netherlands)

    T.W. Kuijpers (Taco W.); E.M.M. van Leeuwen (Ester); B.H. Barendregt (Barbara); P. Klarenbeek (Paul); D.J. Aan de Kerk (Daan); P.A. Baars (Paul); M.H. Jansen (Machiel H.); N. de Vries (Nicolette); R.A.W. van Lier (Rene); M. van der Burg (Mirjam)

    2013-01-01

    textabstractMutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B+T-NK-X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined

  14. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

    NARCIS (Netherlands)

    Kuijpers, Taco W.; van Leeuwen, Ester M. M.; Barendregt, Barbara H.; Klarenbeek, Paul; Aan de Kerk, Daan J.; Baars, Paul A.; Jansen, Machiel H.; de Vries, Niek; van Lier, René A. W.; van der Burg, Mirjam

    2013-01-01

    Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined

  15. Long term treatment of severe obesity: four year follow up of results of combined behavioural modification programme.

    Science.gov (United States)

    Björvell, H; Rössner, S

    1985-01-01

    A four year programme of treatment for severe obesity combining standard techniques such as behavioural modification, exercise, nutritional advice, and, in addition, readmission of patients who relapse has been developed. One hundred and seven subjects of both sexes were treated. Thirty nine had their jaws fixed from the start. After four years 104 out of 107 subjects were traced; 33 (31%) had left the programme. The mean loss of weight in the remaining 74 subjects was 11.7 kg (range -20 to 55.5): 14 had lost more than 20 kg, 35 had lost 5-20 kg, 17 had lost 0-5 kg, and eight were above their weight before treatment. The rate of dropping out in this study was lower than that generally reported. Our data suggest that combined behavioural modification used as a programme for reducing weight may result in a substantial loss of weight for several years even for severely obese subjects. PMID:3926201

  16. Esthetic Rehabilitation of a Severely Compromised Anterior Area: Combined Periodontal and Restorative Approach

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    Rachele Censi

    2014-01-01

    Full Text Available The complete oral rehabilitation of patients demanding a beautiful and attractive smile involves a multidisciplinary approach that includes the change of both the morphological aspect of the teeth and the architecture of gum tissues. This clinical report describes a successful interdisciplinary approach for the treatment of an esthetically compromised dentition. In a first phase, the periodontal plastic surgery was performed for root coverage and, in particular, it was decided for the execution of a coronally advanced flap for the treatment of multiple recession defects. Once complete healing of soft tissues was obtained, six lithium disilicate veneers were placed over the anterior maxillary teeth. Lithium disilicate is a glass-based ceramic which presents excellent aesthetics and allows the passage of light without creating unnatural reflections. This feature has made it possible to recreate a natural aspect of teeth that in combination with the harmonic architecture of soft tissue has permitted obtaining a beautiful and pleasant smile.

  17. Esthetic rehabilitation of a severely compromised anterior area: combined periodontal and restorative approach.

    Science.gov (United States)

    Censi, Rachele; Vavassori, Virna; Borgonovo, Andrea Enrico; Re, Dino

    2014-01-01

    The complete oral rehabilitation of patients demanding a beautiful and attractive smile involves a multidisciplinary approach that includes the change of both the morphological aspect of the teeth and the architecture of gum tissues. This clinical report describes a successful interdisciplinary approach for the treatment of an esthetically compromised dentition. In a first phase, the periodontal plastic surgery was performed for root coverage and, in particular, it was decided for the execution of a coronally advanced flap for the treatment of multiple recession defects. Once complete healing of soft tissues was obtained, six lithium disilicate veneers were placed over the anterior maxillary teeth. Lithium disilicate is a glass-based ceramic which presents excellent aesthetics and allows the passage of light without creating unnatural reflections. This feature has made it possible to recreate a natural aspect of teeth that in combination with the harmonic architecture of soft tissue has permitted obtaining a beautiful and pleasant smile.

  18. Effect of the mixing ratio during co-treatment of landfill leachate and sewage with a combined stripping and reversed A²/O process.

    Science.gov (United States)

    Zeng, Xiao-lan; Ding, Wen-chuan; Zhang, Zhi; Wan, Peng; Deng, Yang; Wang, Shuangshuang

    2015-01-01

    In this study, pilot-scale tests were conducted to evaluate the effect of volumetric mixing ratio of landfill leachate to sewage on the performance of the combined ammonia stripping and reversed anaerobic/anoxic/oxic (A(2)/O) process for co-treatment of landfill leachate and municipal sewage. Stripping, as pre-treatment, could significantly remove ammonia nitrogen (NH3-N) and total nitrogen (TN) by 55% and 52%, respectively. Moreover, chemical oxygen demand (COD) was slightly reduced by 6.8%, and little total phosphorus (TP) was removed. The subsequent reversed A(2)/O process appeared to be highly influenced by the volumetric mixing ratio of leachate to sewage. Typically, the effluent COD, NH3-N, TN and TP increased with the increasing ratio from 1:30 to 1:15, namely, the increasing fraction of leachate. Over the all tested mixing ratio range, the effluent COD and NH3-N were satisfied with the primary B standards of Chinese Discharge Standard of Pollutants for municipal waste water treatment plant (GB18918-2002). The standards different from the primary A standards for water reuse are used for discharge into the most surface water bodies in China. However, TN and TP would exceed the primary B standard levels at a mixing ratio of 1:15 or greater. These findings suggest that an appropriate volumetric mixing ratio should be carefully selected to ensure the performance of the reversed A(2)/O process.

  19. Outcomes of Combined Shelf Acetabuloplasty with Femoral Varus Osteotomy in Severe Legg-Calve-Perthes (LCP) Disease: Advanced Containment Method for Severe LCP Disease.

    Science.gov (United States)

    Lim, Kyung Sup; Shim, Jong Sup

    2015-12-01

    Standard treatments may provide adequate containment in mild to moderate Legg-Calve-Perthes disease (LCPD), but they can be problematic in more severe cases. The purpose of this study was to report the results of combined shelf acetabuloplasty with femoral varus osteotomy in severe LCPD. We reviewed 12 patients who had undergone combined shelf acetabuloplasty with femoral varus osteotomy. The indications for this type of operation were: (1) above 8 years of age at clinical onset; (2) massive femoral epiphysis involvement (Catterall group 4, lateral pillar C); (3) femoral head lateral subluxation on the anteroposterior radiograph; and (4) impending hinged abduction on preoperative magnetic resonance imaging or arthrography. The mean age was 9.3 years (range, 8 to 10.8 years). The patients were clinically evaluated with Iowa hip score and leg length discrepancy at the final follow-up. Radiographic outcome was assessed using the Stulberg classification to evaluate femoral head sphericity. The presence of osteoarthritis was evaluated by the Tonnis classification. Correlation analysis was conducted to analyze the preoperative factors that were strongly associated with patients' outcomes. The mean follow-up period was 10.1 years (range, 7.1 to 13.2 years). Functional grade was excellent in all patients at last follow-up (mean, 92; range, 82 to 99). The mean leg length discrepancy after skeletal maturity was 0.9 cm (range, 0 to 1.7 cm). There were no significant complications or need for additional surgery. Radiographically, 92% of patients reached satisfactory outcomes: Stulberg grade I, 0 cases; Stulberg grade II, 4 cases (34%); Stulberg III, 7 cases (58%), Stulberg IV, 1 case (8%); and Stulberg V, 0 cases. There was no osteoarthritis by Tonnis classification. The surgical outcomes for combined shelf acetabuloplasty with femoral varus osteotomy in severe LCPD patients over 8 years old are comparable with other advanced surgical methods. In the cases of severe disease

  20. Combined orthodontic and surgical treatment of severe mandibular laterognathie with bimaxillary protrusion: case report.

    Science.gov (United States)

    Sayinsu, Korkmaz; Isik, Fulya

    2007-01-01

    This article summarizes the treatment progress for a patient with a severe dolichofacial pattern with a convex profile, severe lip incompetency, and concomitant mouth breathing. Her maxillary occlusal plane had a cant and the maxillary and mandibular midlines were shifted 2 and 4 mm to the left side, respectively. The treatment plan summary was as follows: (1) maxillary rapid expansion for the elimination of maxillary constriction; (2) extraction of maxillary right first molar; (3) extraction of mandibular first premolars; (4) preoperative orthodontic treatment to correct dental protrusions; (5) surgical repositioning of the maxilla and mandible; and (6) postoperative orthodontic treatment and retention. Orthodontic treatment lasted a total of 28 months, with a good intercuspation and significantly improved facial esthetics at the end of treatment. The 1-year postretention lateral cephalometric measurements did not indicate any significant relapse. Dental protrusion and crowding in both jaws were eliminated. Facial and dental asymmetry was resolved and the profile was improved. The cant of the occlusal plane and the lips were corrected. Evaluation of pre- and posttreatment profiles revealed a decrease in convexity. Dentally, Class I canine and Class III molar relationships were present at the end of the treatment. Maxillary and mandibular incisors were uprighted, improving the interincisal angle and the bite relationship.

  1. Efficacy of a combined intracerebral and systemic gene delivery approach for the treatment of a severe lysosomal storage disorder.

    Science.gov (United States)

    Spampanato, Carmine; De Leonibus, Elvira; Dama, Paola; Gargiulo, Annagiusi; Fraldi, Alessandro; Sorrentino, Nicolina Cristina; Russo, Fabio; Nusco, Edoardo; Auricchio, Alberto; Surace, Enrico M; Ballabio, Andrea

    2011-05-01

    Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1(-/-)) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrations-either directly in brain, or systemic alone -in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the "combined" mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders.

  2. Severe Hypernatremia Caused by Acute Exogenous Salt Intake Combined with Primary Hypothyroidism.

    Science.gov (United States)

    Jung, Woo Jin; Park, Su Min; Park, Jong Man; Rhee, Harin; Kim, Il Young; Lee, Dong Won; Lee, Soo Bong; Seong, Eun Young; Kwak, Ihm Soo; Song, Sang Heon

    2016-12-01

    This report describes a case of severe hypernatremia with a serum sodium concentration of 188.1mmol/L caused by exogenous salt intake. A 26-year-old man diagnosed with Crohn's disease 5 years previously visited our clinic due to generalized edema and personality changes, with aggressive behavior. He had compulsively consumed salts, ingesting approximately 154 g of salt over the last 4 days. Despite careful fluid management that included not only hypotonic fluid therapy for 8 hours but also hypertonic saline administration, his serum sodium level decreased sharply at 40.6 mmol/L; however, it returned to normal within 72-hour of treatment without any neurological deficits. Primary hypothyroidism was also diagnosed. He was discharged after 9 days from admission, with a stable serum sodium level. We have described the possibility of successful treatment in a patient with hypernatremia caused by acute salt intoxication without sustained hypotonic fluid therapy.

  3. Biallelic modification of IL2RG leads to severe combined immunodeficiency in pigs

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    Jung-Taek Kang

    2016-11-01

    Full Text Available Abstracts Background Pigs with SCID can be a useful model in regenerative medicine, xenotransplantation, and cancer cell transplantation studies. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, we report generation and phenotypic characterization of IL2RG knockout female pigs produced through combination of CRISPR/Cas9 system and SCNT. As expected, pigs lacking IL2RG presented SCID phenotype. Methods First, specific CRISPR/Cas9 systems targeting IL2RG were introduced into developing pig embryos then the embryos were transferred into surrogates. A total of six fetuses were obtained from the embryo transfer and fetal fibroblast cell lines were established. Then IL2RG knockout female cells carrying biallelic genetic modification were used as donor cells for SCNT, followed by embryo transfer. Results Three live cloned female piglets carrying biallelic mutations in IL2RG were produced. All cloned piglets completely lacked thymus and they had a significantly reduced level of mature T, B and NK cells in their blood and spleen. Conclusions Here, we generated IL2RG knockout female pigs showing phenotypic characterization of SCID. This IL2RG knockout female pigs will be a promising model for biomedical and translational research.

  4. The combined using of ustekinumab and narrow-band phototherapy in treatment of severe psoriasis

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    Kruglova L.S.

    2015-09-01

    Full Text Available Aim: research the effectiveness of UVB 311 nm phototherapy in patients with the "escape effect" that developed in the 44th — 56th weeks of the ustekinumab use. Materials and Methods. The examination and treatment of 9 patients with extensive psoriasis vulgaris receiving ustekinumab by hypodermic injection at a dose of 45 mg if body weight of the patient not more than 100 kg, and 90 mg of body weight over than 100 kg, on the zero week, the 4th week and then every 12 weeks. Among them 6 (66,7% men and 3 (33,3% women aged from 28 to 65 years. All patients in the 44th — 56th weeks of ustekinumab observed effect of "escape" in connection with which he has been appointed narrowband phototherapy. Results. The combined use of ustekinumab and UVB 311 nm phototherapy in patients with "escape effect" contributes to the marked regression of clinical symptoms and allows you to control the process for long, which is confirmed by the dynamics of the index PASI, BSA and DLQI. Conclusion. In the case of the effect of "escape" in the application of biological therapy drugs (ustekinumab possible appointment of a narrow-band medium wave phototherapy course 25-30 procedures.

  5. Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides

    Science.gov (United States)

    Vacas-Córdoba, Enrique; Galán, Marta; de la Mata, Francisco J; Gómez, Rafael; Pion, Marjorie; Muñoz-Fernández, M Ángeles

    2014-01-01

    Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV)-1 infection rates. Up until now, antiretrovirals (ARVs) have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16) and naphthyl sulfonated (G2-NF16) ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as potential microbicides to block the sexual transmission of HIV-1. PMID:25114528

  6. Rapid and visual detection of human enterovirus coxsackievirus A16 by reverse transcription loop-mediated isothermal amplification combined with lateral flow device.

    Science.gov (United States)

    Yan, G; Jun, L; Kangchen, Z; Yiyue, G; Yang, Y; Xiaoyu, Z; Zhiyang, S; Lunbiao, C

    2015-12-01

    In this study, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with lateral flow device (LFD) technology to rapidly detect CVA16 was developed and evaluated. RT-LAMP assay was optimized to amplify VP1 gene of CVA16. Amplified products were analysed by LFD and capillary electrophoresis. The RT-LAMP-LFD assay showed 100% specificity in detecting CVA16, and showed analytical sensitivity of 0·55 TCID50 per reaction mixture. Comparison of the RT-LAMP-LFD assay with real-time RT-PCR developed previously in clinical specimens showed 93·3% agreement. The RT-LAMP-LFD assay is more sensitive in detecting CVA16 RNA. The RT-LAMP-LFD assay presented here might offer a rapid and simple alternative in clinical diagnosis of CVA16. Coxsackievirus A16 (CVA16) is one of the major causative agents of hand, foot and mouth disease (HFMD). Rapid and reliable detection and typing of it can limit the spread. We developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with lateral flow device (LFD) technology to rapidly detect CVA16. The high sensitivity and specificity and its ease of use make this assay ideal for use in resource-limited settings such as primary care facilities and clinical laboratories in developing countries. © 2015 The Society for Applied Microbiology.

  7. Interactions of Organics within Hydrated Selective Layer of Reverse Osmosis Desalination Membrane: A Combined Experimental and Computational Study.

    Science.gov (United States)

    Ghoufi, Aziz; Dražević, Emil; Szymczyk, Anthony

    2017-03-07

    In this work we have examined a computational approach in predicting the interactions between uncharged organic solutes and polyamide membranes. We used three model organic molecules with identical molecular weights (100.1 g/mol), 4-aminopiperidine, 3,3-dimethyl-2-butanone (pinacolone) and methylisobutyl ketone for which we obtained experimental data on partitioning, diffusion and separation on a typical seawater reverse osmosis (RO) membrane. The interaction energy between the solutes and the membrane phase (fully aromatic polyamide) was computed from molecular dynamics (MD) simulations and the resulting sequence was found to correlate well with the experimental rejections and sorption data. Sorption of the different organic solutes within the membrane skin layer determined from attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) nicely agreed with interaction energies computed from molecular simulations. Qualitative information about solute diffusivity inside the membrane was also extracted from MD simulations while ATR-FTIR experiments indicated strongly hindered diffusion with diffusion coefficients in the membrane about 10-15 m2/s. The computational approach presented here could be a first step toward predicting rejections trends of, for example, hormones and pharmaceuticals by RO dense membranes.

  8. Sterile Reverse Osmosis Water Combined with Friction Are Optimal for Channel and Lever Cavity Sample Collection of Flexible Duodenoscopes

    Directory of Open Access Journals (Sweden)

    Michelle J. Alfa

    2017-11-01

    Full Text Available IntroductionSimulated-use buildup biofilm (BBF model was used to assess various extraction fluids and friction methods to determine the optimal sample collection method for polytetrafluorethylene channels. In addition, simulated-use testing was performed for the channel and lever cavity of duodenoscopes.Materials and methodsBBF was formed in polytetrafluorethylene channels using Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Sterile reverse osmosis (RO water, and phosphate-buffered saline with and without Tween80 as well as two neutralizing broths (Letheen and Dey–Engley were each assessed with and without friction. Neutralizer was added immediately after sample collection and samples concentrated using centrifugation. Simulated-use testing was done using TJF-Q180V and JF-140F Olympus duodenoscopes.ResultsDespite variability in the bacterial CFU in the BBF model, none of the extraction fluids tested were significantly better than RO. Borescope examination showed far less residual material when friction was part of the extraction protocol. The RO for flush-brush-flush (FBF extraction provided significantly better recovery of E. coli (p = 0.02 from duodenoscope lever cavities compared to the CDC flush method.Discussion and conclusionWe recommend RO with friction for FBF extraction of the channel and lever cavity of duodenoscopes. Neutralizer and sample concentration optimize recovery of viable bacteria on culture.

  9. Reversal of arsenic-induced hepatic apoptosis with combined administration of DMSA and its analogues in guinea pigs: role of glutathione and linked enzymes.

    Science.gov (United States)

    Mishra, Deepshikha; Mehta, Ashish; Flora, Swaran J S

    2008-02-01

    Arsenicosis, due to contaminated drinking water in the Indo-Bangladesh region, is a serious health hazard in terms of morbidity and mortality. Reactive oxygen species (ROS) generated due to arsenic toxicity have been attributed as one of the initial signals that impart cellular toxicity, which is controlled by the internal antioxidant glutathione (GSH). In the present study, we investigated (i) the role of GSH and its linked enzymes, glutathione peroxidase and glutathione reductase, in reversing chronic arsenic toxicity using a thiol chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), or one of its analogues individually or in combination; (ii) if alterations in the carbon side chain of DMSA increased efficacy; and (iii) whether the combination therapy enhance arsenic removal from hepatic tissue and prevent hepatic apoptosis. Results indicated that chronic arsenic exposure led to a ROS-mediated, mitochondrial-driven, caspase-dependent apoptosis in hepatic cells with a significant increase in glutathione disulfide (GSSG) levels and decreased glutathione reductase levels. Monotherapy with DMSA and its analogues did show minimal recovery postchelation. However, the combination of DMSA with long carbon chain analogues like monoisoamyl DMSA (MiADMSA) or monocyclohexyl DMSA (MchDMSA) showed a better efficacy in terms of reducing the arsenic burden as well as reversing altered biochemical variables indicative of oxidative stress and apoptosis. We also observed that GSH and its linked enzymes, especially glutathione reductase, play a vital role in scavenging ROS, maintaining GSH pools, and providing clinical recoveries. On the basis of the above observations, we recommend that combinational therapy of DMSA and its long carbon chain analogues MiADMSA or MchDMSA would be more effective in arsenic toxicity.

  10. Rapid differentiation and identification of potential severe strains of Citrus tristeza virus by real-time reverse transcription-polymerase chain reaction assays.

    Science.gov (United States)

    Yokomi, R K; Saponari, M; Sieburth, P J

    2010-04-01

    A multiplex Taqman-based real-time reverse transcription (RT) polymerase chain reaction (PCR) assay was developed to identify potential severe strains of Citrus tristeza virus (CTV) and separate genotypes that react with the monoclonal antibody MCA13. Three strain-specific probes were developed using intergene sequences between the major and minor coat protein genes (CPi) in a multiplex reaction. Probe CPi-VT3 was designed for VT and T3 genotypes; probe CPi-T36 for T36 genotypes; and probe CPi-T36-NS to identify isolates in an outgroup clade of T36-like genotypes mild in California. Total nucleic acids extracted by chromatography on silica particles, sodium dodecyl sulfate-potassium acetate, and CTV virion immunocapture all yielded high quality templates for real-time PCR detection of CTV. These assays successfully differentiated CTV isolates from California, Florida, and a large panel of CTV isolates from an international collection maintained in Beltsville, MD. The utility of the assay was validated using field isolates collected in California and Florida.

  11. Recombination activating gene-2null severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently

    OpenAIRE

    Choi, Yun-Jung; Kim, Eunsu; Reza, Abu Musa Md Talimur; Hong, Kwonho; Song, Hyuk; Park, Chankyu; Cho, Seong-Keun; Lee, Kiho; Prather, Randall S.; Kim, Jin-Hoi

    2017-01-01

    This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3+-, CD4+-, and CD8+ signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFAT...

  12. {sup 18}F-fluorodeoxyglucose positron emission tomography combined with whole-body computed tomographic angiography in critically ill patients with suspected severe sepsis with no definite diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Mandry, Damien [CHU Nancy, Pole d' imagerie, Nancy (France); University of Lorraine, Faculty of Medicine, Nancy (France); INSERM, UMR 947, Nancy (France); Tatopoulos, Alexis; Lemarie, Jeremie; Bollaert, Pierre-Edouard; Gibot, Sebastien [University of Lorraine, Faculty of Medicine, Nancy (France); CHU de Nancy - Hopital Central, Service de Reanimation Medicale, Nancy (France); INSERM, UMR 1116, Nancy (France); Chevalier-Mathias, Elodie [CHU Nancy, Pole d' imagerie, Nancy (France); INSERM, UMR 947, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France); Roch, Veronique [CHU Nancy, Pole d' imagerie, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France); Olivier, Pierre [CHU Nancy, Pole d' imagerie, Nancy (France); University of Lorraine, Faculty of Medicine, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France); Marie, Pierre-Yves [CHU Nancy, Pole d' imagerie, Nancy (France); University of Lorraine, Faculty of Medicine, Nancy (France); INSERM, UMR 1116, Nancy (France); Nancyclotep, Experimental Imaging Platform, Nancy (France)

    2014-10-15

    Timely identification of septic foci is critical in patients with severe sepsis or septic shock of unknown origin. This prospective pilot study aimed to assess {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET), combined with whole-body computed tomographic angiography (CTA), in patients with suspected severe sepsis and for whom the prior diagnostic workup had been inconclusive. Patients hospitalized in an intensive care unit with a suspected severe sepsis but no definite diagnosis after 48 h of extensive investigations were prospectively included and referred for a whole body FDG-PET/CTA. Results from FDG-PET/CTA were assessed according to the final diagnosis obtained after follow-up and additional diagnostic workup. Seventeen patients were prospectively included, all on mechanical ventilation and 14 under vasopressor drugs. The FDG-PET/CTA exam 1) was responsible for only one desaturation and one hypotension, both quickly reversible under treatment; 2) led to suspect 16 infectious sites among which 13 (81 %) could be confirmed by further diagnostic procedures; and 3) triggered beneficial changes in the medical management of 12 of the 17 study patients (71 %). The FDG-PET/CTA images showed a single or predominant infectious focus in two cases where CTA was negative and in three cases where CTA exhibited multiple possible foci. Whole-body FDG-PET/CTA appears to be feasible, relatively safe, and provides reliable and useful information, when prospectively planned in patients with suspected severe sepsis and for whom prior diagnostic workup had been inconclusive. The FDG-PET images are particularly helpful when CTA exhibits no or multiple possible sites. (orig.)

  13. Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338

    Directory of Open Access Journals (Sweden)

    McIntosh Kenneth

    2007-02-01

    Full Text Available Abstract Background The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI resistant codons for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART was studied. Results There were few primary PI associated mutations in this PI-naïve population, but 84% had NRTI mutations – codons 215 (66%, 41 (42%, 67 (37%, 210 (33% and 70 (32%. None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006. Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017. Conclusion No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.

  14. Cross Time-Frequency Analysis for Combining Information of Several Sources: Application to Estimation of Spontaneous Respiratory Rate from Photoplethysmography

    Directory of Open Access Journals (Sweden)

    M. D. Peláez-Coca

    2013-01-01

    Full Text Available A methodology that combines information from several nonstationary biological signals is presented. This methodology is based on time-frequency coherence, that quantifies the similarity of two signals in the time-frequency domain. A cross time-frequency analysis method, based on quadratic time-frequency distribution, has been used for combining information of several nonstationary biomedical signals. In order to evaluate this methodology, the respiratory rate from the photoplethysmographic (PPG signal is estimated. The respiration provokes simultaneous changes in the pulse interval, amplitude, and width of the PPG signal. This suggests that the combination of information from these sources will improve the accuracy of the estimation of the respiratory rate. Another target of this paper is to implement an algorithm which provides a robust estimation. Therefore, respiratory rate was estimated only in those intervals where the features extracted from the PPG signals are linearly coupled. In 38 spontaneous breathing subjects, among which 7 were characterized by a respiratory rate lower than 0.15 Hz, this methodology provided accurate estimates, with the median error {0.00; 0.98} mHz ({0.00; 0.31}% and the interquartile range error {4.88; 6.59} mHz ({1.60; 1.92}%. The estimation error of the presented methodology was largely lower than the estimation error obtained without combining different PPG features related to respiration.

  15. Cross Time-Frequency Analysis for Combining Information of Several Sources: Application to Estimation of Spontaneous Respiratory Rate from Photoplethysmography

    Science.gov (United States)

    Peláez-Coca, M. D.; Orini, M.; Lázaro, J.; Bailón, R.; Gil, E.

    2013-01-01

    A methodology that combines information from several nonstationary biological signals is presented. This methodology is based on time-frequency coherence, that quantifies the similarity of two signals in the time-frequency domain. A cross time-frequency analysis method, based on quadratic time-frequency distribution, has been used for combining information of several nonstationary biomedical signals. In order to evaluate this methodology, the respiratory rate from the photoplethysmographic (PPG) signal is estimated. The respiration provokes simultaneous changes in the pulse interval, amplitude, and width of the PPG signal. This suggests that the combination of information from these sources will improve the accuracy of the estimation of the respiratory rate. Another target of this paper is to implement an algorithm which provides a robust estimation. Therefore, respiratory rate was estimated only in those intervals where the features extracted from the PPG signals are linearly coupled. In 38 spontaneous breathing subjects, among which 7 were characterized by a respiratory rate lower than 0.15 Hz, this methodology provided accurate estimates, with the median error {0.00; 0.98} mHz ({0.00; 0.31}%) and the interquartile range error {4.88; 6.59} mHz ({1.60; 1.92}%). The estimation error of the presented methodology was largely lower than the estimation error obtained without combining different PPG features related to respiration. PMID:24363777

  16. A Combination of Intrastromal and Intracameral Injections of Amphotericin B in the Treatment of Severe Fungal Keratitis

    Directory of Open Access Journals (Sweden)

    Jianzhang Hu

    2016-01-01

    Full Text Available Purpose. To evaluate the efficacy of a combination of intrastromal and intracameral injections of amphotericin B in the treatment of severe recalcitrant fungal keratitis. Methods. Patients with severe fungal keratitis who were resistant to conventional antifungal medical treatments and needed potential surgical intervention were recruited at the First Affiliated Hospital of Fujian Medical University between January 2012 and July 2013. The patients were treated with a combination of intrastromal and intracameral injections of amphotericin B (25 μg/mL and 50 μg/mL, resp.. Selectively repeated injections were performed as necessary. The efficacy, complications, and outcome were evaluated. Results. Nine patients (9 eyes were involved in this study. All 9 cases responded favorably, and the clinical appearance of serious corneal damage and intraocular extension was resolved after the treatment. Four eyes required only 1 injection, and 5 eyes required repeated injections. Seven corneal ulcers healed with leucoma, and 2 healed with adherent leucoma. All of our cases had a marked increase in the anterior chamber reaction and pain immediately after the injection. There was no obvious clinical evidence of corneal or lenticular toxicity in any patient. Conclusions. A combination of intrastromal and intracameral injections of amphotericin B may be safe and effective for the treatment of severe fungal keratitis that is resistant to conventional therapy.

  17. A Combination of Intrastromal and Intracameral Injections of Amphotericin B in the Treatment of Severe Fungal Keratitis.

    Science.gov (United States)

    Hu, Jianzhang; Zhang, Jingjin; Li, Yanling; Han, Xiaoli; Zheng, Weidong; Yang, Juan; Xu, Guoxing

    2016-01-01

    Purpose . To evaluate the efficacy of a combination of intrastromal and intracameral injections of amphotericin B in the treatment of severe recalcitrant fungal keratitis. Methods . Patients with severe fungal keratitis who were resistant to conventional antifungal medical treatments and needed potential surgical intervention were recruited at the First Affiliated Hospital of Fujian Medical University between January 2012 and July 2013. The patients were treated with a combination of intrastromal and intracameral injections of amphotericin B (25  μ g/mL and 50  μ g/mL, resp.). Selectively repeated injections were performed as necessary. The efficacy, complications, and outcome were evaluated. Results . Nine patients (9 eyes) were involved in this study. All 9 cases responded favorably, and the clinical appearance of serious corneal damage and intraocular extension was resolved after the treatment. Four eyes required only 1 injection, and 5 eyes required repeated injections. Seven corneal ulcers healed with leucoma, and 2 healed with adherent leucoma. All of our cases had a marked increase in the anterior chamber reaction and pain immediately after the injection. There was no obvious clinical evidence of corneal or lenticular toxicity in any patient. Conclusions . A combination of intrastromal and intracameral injections of amphotericin B may be safe and effective for the treatment of severe fungal keratitis that is resistant to conventional therapy.

  18. Severe 2010 cold-water event caused unprecedented mortality to corals of the Florida reef tract and reversed previous survivorship patterns.

    Directory of Open Access Journals (Sweden)

    Diego Lirman

    Full Text Available BACKGROUND: Coral reefs are facing increasing pressure from natural and anthropogenic stressors that have already caused significant worldwide declines. In January 2010, coral reefs of Florida, United States, were impacted by an extreme cold-water anomaly that exposed corals to temperatures well below their reported thresholds (16°C, causing rapid coral mortality unprecedented in spatial extent and severity. METHODOLOGY/PRINCIPAL FINDINGS: Reef surveys were conducted from Martin County to the Lower Florida Keys within weeks of the anomaly. The impacts recorded were catastrophic and exceeded those of any previous disturbances in the region. Coral mortality patterns were directly correlated to in-situ and satellite-derived cold-temperature metrics. These impacts rival, in spatial extent and intensity, the impacts of the well-publicized warm-water bleaching events around the globe. The mean percent coral mortality recorded for all species and subregions was 11.5% in the 2010 winter, compared to 0.5% recorded in the previous five summers, including years like 2005 where warm-water bleaching was prevalent. Highest mean mortality (15%-39% was documented for inshore habitats where temperatures were <11°C for prolonged periods. Increases in mortality from previous years were significant for 21 of 25 coral species, and were 1-2 orders of magnitude higher for most species. CONCLUSIONS/SIGNIFICANCE: The cold-water anomaly of January 2010 caused the worst coral mortality on record for the Florida Reef Tract, highlighting the potential catastrophic impacts that unusual but extreme climatic events can have on the persistence of coral reefs. Moreover, habitats and species most severely affected were those found in high-coral cover, inshore, shallow reef habitats previously considered the "oases" of the region, having escaped declining patterns observed for more offshore habitats. Thus, the 2010 cold-water anomaly not only caused widespread coral mortality

  19. Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Sørensen, Hanne Thykjær; Norengaard, Lisbeth

    2007-01-01

    BACKGROUND: Most patients with severe hemophilia A suffer from a profoundly compromised hemostatic response. In addition to both the delayed and slow development of a clot, previous studies have documented that severe hemophilia A is also associated with reduced clot stability. OBJECTIVES: We...... examined whether the clot stability in hemophiliacs could be improved by treatment with tranexamic acid (TXA) in combination with recombinant factor VIII (rFVIII). PATIENTS/METHODS: Baseline blood samples were obtained from eight males with severe hemophilia A. Thereafter, a bolus injection of r...... the elasticity curve increased 5-fold after rFVIII and 24-fold after addition of TXA. CONCLUSIONS: The study demonstrates that simultaneous treatment with TXA and rFVIII significantly improves the clot stability in patients with hemophilia A. Udgivelsesdato: December...

  20. Evaluation of contaminant removal of reverse osmosis and advanced oxidation in full-scale operation by combining passive sampling with chemical analysis and bioanalytical tools.

    Science.gov (United States)

    Escher, Beate I; Lawrence, Michael; Macova, Miroslava; Mueller, Jochen F; Poussade, Yvan; Robillot, Cedric; Roux, Annalie; Gernjak, Wolfgang

    2011-06-15

    Advanced water treatment of secondary treated effluent requires stringent quality control to achieve a water quality suitable for augmenting drinking water supplies. The removal of micropollutants such as pesticides, industrial chemicals, endocrine disrupting chemicals (EDC), pharmaceuticals, and personal care products (PPCP) is paramount. As the concentrations of individual contaminants are typically low, frequent analytical screening is both laborious and costly. We propose and validate an approach for continuous monitoring by applying passive sampling with Empore disks in vessels that were designed to slow down the water flow, and thus uptake kinetics, and ensure that the uptake is only marginally dependent on the chemicals' physicochemical properties over a relatively narrow molecular size range. This design not only assured integrative sampling over 27 days for a broad range of chemicals but also permitted the use of a suite of bioanalytical tools as sum parameters, representative of mixtures of chemicals with a common mode of toxic action. Bioassays proved to be more sensitive than chemical analysis to assess the removal of organic micropollutants by reverse osmosis, followed by UV/H₂O₂ treatment, as many individual compounds fell below the quantification limit of chemical analysis, yet still contributed to the observed mixture toxicity. Nonetheless in several cases, the responses in the bioassays were also below their quantification limits and therefore only three bioassays were evaluated here, representing nonspecific toxicity and two specific end points for estrogenicity and photosynthesis inhibition. Chemical analytical techniques were able to quantify 32 pesticides, 62 PCPPs, and 12 EDCs in reverse osmosis concentrate. However, these chemicals could explain only 1% of the nonspecific toxicity in the Microtox assay in the reverse osmosis concentrate and 0.0025% in the treated water. Likewise only 1% of the estrogenic effect in the E-SCREEN could be

  1. Combining Robotic Training and Non-Invasive Brain Stimulation in Severe Upper Limb-Impaired Chronic Stroke Patients

    Directory of Open Access Journals (Sweden)

    Vincenzo eDi Lazzaro

    2016-03-01

    Full Text Available Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements.Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomised, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity.20 severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. 8 real and 9 sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes.The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%. The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient improved more in the real than in the sham cTBS group.This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke.

  2. Combining Robotic Training and Non-Invasive Brain Stimulation in Severe Upper Limb-Impaired Chronic Stroke Patients.

    Science.gov (United States)

    Di Lazzaro, Vincenzo; Capone, Fioravante; Di Pino, Giovanni; Pellegrino, Giovanni; Florio, Lucia; Zollo, Loredana; Simonetti, Davide; Ranieri, Federico; Brunelli, Nicoletta; Corbetto, Marzia; Miccinilli, Sandra; Bravi, Marco; Milighetti, Stefano; Guglielmelli, Eugenio; Sterzi, Silvia

    2016-01-01

    Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements. Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS) was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%). The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient) improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke.

  3. Mutations in linker for activation of T cells (LAT) lead to a novel form of severe combined immunodeficiency.

    Science.gov (United States)

    Bacchelli, Chiara; Moretti, Federico A; Carmo, Marlene; Adams, Stuart; Stanescu, Horia C; Pearce, Kerra; Madkaikar, Manisha; Gilmour, Kimberly C; Nicholas, Adeline K; Woods, C Geoffrey; Kleta, Robert; Beales, Phil L; Qasim, Waseem; Gaspar, H Bobby

    2017-02-01

    Signaling through the T-cell receptor (TCR) is critical for T-cell development and function. Linker for activation of T cells (LAT) is a transmembrane adaptor signaling molecule that is part of the TCR complex and essential for T-cell development, as demonstrated by LAT-deficient mice, which show a complete lack of peripheral T cells. We describe a pedigree affected by a severe combined immunodeficiency phenotype with absent T cells and normal B-cell and natural killer cell numbers. A novel homozygous frameshift mutation in the gene encoding for LAT was identified in this kindred. Genetic, molecular, and functional analyses were used to identify and characterize the LAT defect. Clinical and immunologic analysis of patients was also performed and reported. Homozygosity mapping was used to identify potential defective genes. Sanger sequencing of the LAT gene showed a mutation that resulted in a premature stop codon and protein truncation leading to complete loss of function and loss of expression of LAT in the affected family members. We also demonstrate loss of LAT expression and lack of TCR signaling restoration in LAT-deficient cell lines reconstituted with a synthetic LAT gene bearing this severe combined immunodeficiency mutation. For the first time, the results of this study show that inherited LAT deficiency should be considered in patients with combined immunodeficiency with T-cell abnormalities. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Combined application of distal and proximal embolic protection devices in endovascular stenting for severe carotid artery stenosis

    Directory of Open Access Journals (Sweden)

    Zhi-hua DU

    2011-09-01

    Full Text Available Objective To analyze and summarize methods and experiences of combined application of distal and proximal embolic protection devices(EPD in endovascular stenting for severe carotid artery stenosis.Methods Five patients with severe stenosis of the common carotid artery or with extracranial segment of the internal carotid artery diagnosed through digital subtraction angiography(DSA from March to July 2010 were involved in the present study.All patients received carotid angioplasty and stenting(CAS,with a combination of distal and proximal EPD via the percutaneous femoral artery approach.Results The operation failed in one patient,whereas technical success with no intraoperative complication was achieved in four patients.The symptoms disappeared or improved in the four cases that achieved technical success.The follow-up duration was one to three months,and no cerebral ischemia was found.Conclusion CAS with the combined application of distal and proximal EPD in some special cases of carotid artery stenosis may surmount the shortage of single EPD,reduce the risk of intraoperative embolization,decrease the time of intraoperative endovascular inflow occlusion,and reduce high-risk operations.CAS may be used as an individualized treatment strategy for patients with carotid artery stenosis.

  5. Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    ... and her daughter Every patient — from coping to hoping. Every donor or volunteer — from altruism to inspiration. ... this type of SCID have very few working white blood cells to fight infection. Only boys can ...

  6. Severe Combined Immunodeficiency (SCID)

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  7. Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    ... Applying Timelines for Assignment, Review, & Funding Timeline for Managing Your Grant Apply for a Grant Sample Applications ... Foreign Organization System Review Sample Agenda: FOS Workshops Changes to Project or ... Center Organizational Chart Find NIAID Staff Office of the Director ...

  8. Severe Obesity and Insulin Resistance due to Deletion of the Maternal Gsα Allele Is Reversed by Paternal Deletion of the Gsα Imprint Control Region

    Science.gov (United States)

    Xie, Tao; Chen, Min; Gavrilova, Oksana; Lai, Edwin W.; Liu, Jie; Weinstein, Lee S.

    2008-01-01

    The G protein α-subunit Gsα mediates receptor-stimulated cAMP production and is imprinted with reduced expression from the paternal allele in specific tissues. Disruption of the Gsα maternal (but not paternal) allele leads to severe obesity, hypertriglyceridemia, and insulin resistance in mice and obesity in patients with Albright hereditary osteodystrophy. Paternal deletion of a Gsα imprint control region (1A) leads to loss of tissue-specific Gsα imprinting. To determine whether the metabolic abnormalities resulting from disruption of the Gsα maternal allele could be reversed by loss of paternal Gsα imprinting, females with a heterozygous Gsα exon 1 deletion were mated to males with heterozygous deletion of the imprint control region (1A) to generate mice with maternal Gsα deletion (E1m−), paternal 1A deletion (1Ap−), double mutants (E1m−:1Ap−), and wild type. E1m− mice developed obesity, glucose intolerance, insulin resistance, and hypertriglyceridemia, which were all normalized by the paternal 1A deletion in E1m−:1Ap− mice. Obesity in E1m− was associated with reduced energy expenditure and sympathetic nerve activity, and these were also normalized in E1m−:1Ap− mice. 1Ap− mice had reduced body weight associated with proportional decreases in fat and lean mass as well as increased activity levels. The metabolic phenotype resulting from maternal Gsα deletion is rescued by a genetic lesion that leads to loss of tissue-specific Gsα imprinting, consistent with this phenotype being a direct consequence of Gsα imprinting in one or more specific tissues. PMID:18202131

  9. Hip-inspired implant for revision of failed reverse shoulder arthroplasty with severe glenoid bone loss. Improved clinical outcome in 11 patients at 3-year follow-up.

    Science.gov (United States)

    Uri, Ofir; Bayley, Ian; Lambert, Simon

    2014-04-01

    Glenoid reconstruction and inverted glenoid re-implantation is strongly advocated in revisions of failed reverse shoulder arthroplasty (RSA). Nevertheless, severe glenoid deficiency may preclude glenoid reconstruction and may dictate less favorable solutions, such as conversion to hemiarthropasty or resection arthropasty. The CAD/CAM shoulder (Stanmore Implants, Elstree, UK), a hip arthroplasty-inspired implant, may facilitate glenoid component fixation in these challenging revisions where glenoid reconstruction is not feasible. We questioned (1) whether revision arthroplasty with the CAD/CAM shoulder would alleviate pain and improve shoulder function in patients with failed RSA, not amenable to glenoid reconstruction, (2) whether the CAD/CAM hip-inspired glenoid shell would enable secure and durable glenoid component fixation in these challenging revisions. 11 patients with failed RSAs and unreconstructable glenoids underwent revision with the CAD/CAM shoulder and were followed-up for mean 35 (28-42) months. Clinical outcomes included the Oxford shoulder score, subjective shoulder value, pain rating, physical examination, and shoulder radiographs. The average Oxford shoulder score and subjective shoulder value improved statistically significantly after the revision from 50 to 33 points and from 17% to 48% respectively. Pain rating at rest and during activity improved significantly from 5.3 to 2.3 and from 8.1 to 3.8 respectively. Active forward flexion increased from 25 to 54 degrees and external rotation increased from 9 to 21 degrees. 4 patients required reoperation for postoperative complications. No cases of glenoid loosening occurred. The CAD/CAM shoulder offers an alternative solution for the treatment of failed RSA that is not amenable to glenoid reconstruction.

  10. Combined treatment with chondroitinase ABC and treadmill rehabilitation for chronic severe spinal cord injury in adult rats.

    Science.gov (United States)

    Shinozaki, Munehisa; Iwanami, Akio; Fujiyoshi, Kanehiro; Tashiro, Syoichi; Kitamura, Kazuya; Shibata, Shinsuke; Fujita, Hiroshi; Nakamura, Masaya; Okano, Hideyuki

    2016-12-01

    There are more than 50 times the number of chronic-phase spinal cord injury (SCI) patients than there are acute patients, and over half of all SCI patients are severely disabled. However, research focusing on chronic severe contusional SCI remains very rare. Here, we evaluated whether chondroitinase ABC (C-ABC), a degradative enzyme directed against chondroitin sulfate proteoglycans (CSPGs), and treadmill rehabilitation could exert synergistic therapeutic actions against chronic severe contusional SCI. First, we induced severe contusional SCI in adult rats, and administered C-ABC intrathecally at 6 weeks post-injury for a period of one week. Next, we performed treadmill rehabilitation from weeks 6 to 14 after SCI, for a total period of eight weeks. The initiation of treadmill rehabilitation triggered slight recovery between weeks 6 and 9, whereas C-ABC administration stimulated a third phase of recovery between weeks 12 and 14. Histologically, the C-ABC-treated rats showed an increase in the transverse residual tissue area and the extent of neuronal fiber regeneration at a site caudal to the lesion epicenter, and regrowth of putatively regenerating serotonergic fibers was significantly increased at the epicenter. We suggest that, when combined with intensive rehabilitation, C-ABC may play a beneficial role, even in severe and chronic SCI. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  11. Therapeutic effects of conjunctival flap covering combined with subconjunctival injection of fluconazole on patients with severe fungal corneal ulcer

    Directory of Open Access Journals (Sweden)

    Lin-Shan Shi

    2017-11-01

    Full Text Available AIM:To analyze the clinical efficacy of conjunctival flap covering combined with subconjunctival injection of fluconazole on patients with severe fungal corneal ulcer. METHODS: Totally 50 cases with severe fungal corneal ulcer were collected in our hospital from January 2012 to December 2015. The cases were randomly divided into observation group and control group, 25 cases in each group. All the cases were monocular sick. The control group took single drug treatment, but the observation group were given with conjunctival flap as an extra. The clinical efficacy, best corrected visual acuity and adverse effects rate were observed. And, the relapse of the two groups was followed for 1a. RESULTS: After 1mo of treatment, the clinical curative effect of the observation group was significantly higher than the control group(PPPPCONCLUSION:The conjunctival flap combined with subconjunctival injection of fluconazole has good application value in severe fungal corneal ulcer patients, can effectively improve the clinical curative effect and the visual acuity, and can effectively reduce the incidence of adverse reactions and recurrence rate.

  12. Construction of crystalline 2D covalent organic frameworks with remarkable chemical (acid/base) stability via a combined reversible and irreversible route.

    Science.gov (United States)

    Kandambeth, Sharath; Mallick, Arijit; Lukose, Binit; Mane, Manoj V; Heine, Thomas; Banerjee, Rahul

    2012-12-05

    Two new chemically stable [acid and base] 2D crystalline covalent organic frameworks (COFs) (TpPa-1 and TpPa-2) were synthesized using combined reversible and irreversible organic reactions. Syntheses of these COFs were done by the Schiff base reactions of 1,3,5-triformylphloroglucinol (Tp) with p-phenylenediamine (Pa-1) and 2,5-dimethyl-p-phenylenediamine (Pa-2), respectively, in 1:1 mesitylene/dioxane. The expected enol-imine (OH) form underwent irreversible proton tautomerism, and only the keto-enamine form was observed. Because of the irreversible nature of the total reaction and the absence of an imine bond in the system, TpPa-1 and TpPa-2 showed strong resistance toward acid (9 N HCl) and boiling water. Moreover, TpPa-2 showed exceptional stability in base (9 N NaOH) as well.

  13. Multiplex reverse transcription-polymerase chain reaction combined with on-chip electrophoresis as a rapid screening tool for candidate gene sets

    DEFF Research Database (Denmark)

    Wittig, Rainer; Salowsky, Rüdiger; Blaich, Stephanie

    2005-01-01

    Combining multiplex reverse transcription-polymerase chain reaction (mRT-PCR) with microfluidic amplicon analysis, we developed an assay for the rapid and reliable semiquantitative expression screening of 11 candidate genes for drug resistance in human malignant melanoma. The functionality...... of this approach was demonstrated by low interexperimental variations of amplicon quantities after endpoint analysis. When applied to RNA samples derived from drug-sensitive and -resistant melanoma cell lines, mRT-PCR delivered results qualitatively concordant with data obtained from Northern blot and array...... analyses. The screening of additional melanoma cell lines resulted in distinct expression patterns for ten candidate genes. Our approach reveals a rapid and easy-to-handle alternative for candidate gene set evaluation from limited amounts of RNA....

  14. Rapid and sensitive detection of Laem-Singh virus by reverse transcription loop-mediated isothermal amplification combined with a lateral flow dipstick.

    Science.gov (United States)

    Arunrut, Narong; Seetang-Nun, Yortyot; Phromjai, Jurairat; Panphut, Wattana; Kiatpathomchai, Wansika

    2011-10-01

    Laem-Singh virus (LSNV) was discovered recently in Thailand in farmed Giant Tiger shrimp (Penaeus monodon) displaying signs of slow growth syndrome. Loop-mediated isothermal amplification (LAMP) allows DNA to be amplified rapidly at a constant temperature. Here a reverse transcription (RT)-LAMP method was combined with a chromatographic lateral-flow dipstick (LFD) to detect LSNV RNA rapidly and specifically. The reaction was optimized at 65°C for 30 min and amplified DNA hybridized to an FITC-labeled oligonucleotide probe for 5 min was detected at LFD test line 5 min after application. Including 10 min for rapid RNA extraction, test results could be generated within 1h and did not require electrophoresis. Compared to an existing RT-PCR method, the RT-LAMP-LFD was also ∼1000-fold more sensitive in detecting LSNV RNA. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Successful Therapy of Severe Pseudomembranous Clostridium difficile Colitis Using a Combination of Fecal Microbiota Therapy and Fidaxomicin

    Science.gov (United States)

    Konturek, Peter C.; Haziri, Drilon; Helfritzsch, Harry; Hess, Thomas; Harsch, Igor A.

    2017-01-01

    Objective The aim of this work was to describe the use of a combination of fidaxomicin and fecal microbiota therapy (FMT) in Clostridium difficile infection (CDI). Clinical Presentation and Intervention A 78-year-old female, who was admitted for surgery due to acute diverticulitis caused by postoperative complications and broad antibiotic therapy, developed CDI-induced colitis. Despite the introduction of metronidazole and vancomycin therapy, her clinical condition continued to deteriorate. She was transferred to the intensive care unit where FMT followed by fidaxomicin were performed because her C-reactive protein and leucocyte levels remained elevated. Further clinical improvement and the resolution of colitis was observed. Conclusion In this case, severe CDI colitis was successfully treated with the combination of FMT and fidaxomicin. PMID:27978522

  16. Successful Therapy of Severe Pseudomembranous Clostridium difficile Colitis Using a Combination of Fecal Microbiota Therapy and Fidaxomicin.

    Science.gov (United States)

    Konturek, Peter C; Haziri, Drilon; Helfritzsch, Harry; Hess, Thomas; Harsch, Igor A

    2017-01-01

    The aim of this work was to describe the use of a combination of fidaxomicin and fecal microbiota therapy (FMT) in Clostridium difficile infection (CDI). A 78-year-old female, who was admitted for surgery due to acute diverticulitis caused by postoperative complications and broad antibiotic therapy, developed CDI-induced colitis. Despite the introduction of metronidazole and vancomycin therapy, her clinical condition continued to deteriorate. She was transferred to the intensive care unit where FMT followed by fidaxomicin were performed because her C-reactive protein and leucocyte levels remained elevated. Further clinical improvement and the resolution of colitis was observed. In this case, severe CDI colitis was successfully treated with the combination of FMT and fidaxomicin. © 2016 S. Karger AG, Basel.

  17. Combination of siRNA-directed Gene Silencing With Cisplatin Reverses Drug Resistance in Human Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shanthi Ganesh

    2013-01-01

    Full Text Available One of the most challenging aspects of lung cancer therapy is the rapid acquisition of multidrug-resistant (MDR phenotype. One effective approach would be to identify and downregulate resistance-causing genes in tumors using small interfering RNAs (siRNAs to increase the sensitivity of tumor cells to chemotherapeutic challenge. After identifying the overexpressed resistance-related antiapoptotic genes (survivin and bcl-2 in cisplatin-resistant cells, the siRNA sequences were designed and screened to select the most efficacious candidates. Modifications were introduced in them to minimize off-target effects. Subsequently, the combination of siRNA and cisplatin that gave the maximum synergy was identified in resistant cells. We then demonstrated that the combination treatment of the selected siRNAs and cisplatin encapsulated in CD44-targeting hyaluronic acid (HA-based self-assembling nanosystems reversed the resistance to cisplatin and delayed the tumor growth significantly (growth inhibition increased from 30 to 60% in cisplatin-resistant tumors. In addition, no abnormalities in body weights, liver enzyme levels or histopathology of liver/spleen tissues were observed in any of the treatment groups during the study period. Overall, we demonstrate that the combination of siRNA-mediated gene-silencing strategy with chemotherapeutic agents constitutes a valuable and safe approach for the treatment of MDR tumors.

  18. Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Mikel Sánchez

    2016-01-01

    Full Text Available The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, superficial articular cartilage, synovial fluid, and subchondral bone by combining intra-articular injections and intraosseous infiltrations of platelet rich plasma. We explored a new strategy consisting of intraosseous infiltrations of platelet rich plasma into the subchondral bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously. We assessed the clinical outcomes through osteoarthritis outcome score (KOOS and the inflammatory response by quantifying mesenchymal stem cells in synovial fluid. There was a significant pain reduction in the KOOS from baseline (61.55±14.11 to week 24 (74.60±19.19, after treatment (p=0.008, in the secondary outcomes (symptoms, p=0.004; ADL, p=0.022; sport/rec., p=0.017; QOL, p=0.012, as well as VAS score (p<0.001 and Lequesne Index (p=0.008. The presence of mesenchymal stem cells in synovial fluid and colony-forming cells one week after treatment decreased substantially from 7.98±8.21 MSC/μL to 4.04±5.36 MSC/μL (p=0.019 and from 601.75±312.30 to 139.19±123.61  (p=0.012, respectively. Intra-articular injections combined with intraosseous infiltrations of platelet rich plasma reduce pain and mesenchymal stem cells in synovial fluid, besides significantly improving knee joint function in patients with severe knee osteoarthritis. This trial is registered on EudraCT with the number 2013-003982-32.

  19. Medical Devices; Immunology and Microbiology Devices; Classification of the Newborn Screening Test for Severe Combined Immunodeficiency Disorder. Final order.

    Science.gov (United States)

    2017-10-30

    The Food and Drug Administration (FDA or we) is classifying the newborn screening test for severe combined immunodeficiency disorder (SCID) into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the newborn screening test for SCID's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  20. The comparative effects of lipid, epinephrine, and their combination in the reversal of bupivacaine-induced asystole in the isolated rat heart.

    Science.gov (United States)

    Liu, Le; Xia, Yun; Chen, Ying; Wang, Quanguang; Shi, Tong; Wang, Fangyan; Small, Robert H; Xu, Xuzhong

    2012-04-01

    It remains unclear whether lipid combined with epinephrine is superior or inferior to either drug alone in treating bupivacaine cardiotoxicity. We compared the effects of lipid, epinephrine, and the combination of the two in reversing bupivacaine-induced asystole in the isolated rat heart model. We also measured the effects of lipid, epinephrine, and the combination of the two on bupivacaine content in cardiac tissue. Hearts from male Sprague-Dawley rats were excised and retrograde-perfused in a nonrecirculating Langendorff preparation. Bupivacaine 100 μmol/L was perfused until 3 minutes after asystole. Two percent lipid and 30 μmol/L bupivacaine mixture was then perfused in the lipid group; 0.15 μg/mL epinephrine and 30 μmol/L bupivacaine mixture in the epinephrine group; 2% lipid combined with 0.15 μg/mL epinephrine and 30 μmol/L bupivacaine in the combination group; and 30 μmol/L bupivacaine alone in the control group. Recovery of heartbeat was defined as unassisted regular rhythm with a rate-pressure product (RPP) >10% of baseline for >1 minute. We compared the time from the end of 100 μmol/L bupivacaine infusion to recovery of heartbeat (T(recovery)) for each group. The variables of cardiac function were recorded for 40 minutes after recovery of heartbeat. The cardiac apex of each heart was taken for measurement of the bupivacaine content by liquid chromatography-tandem mass spectrometry at the end of the experiment. Time to recovery (T(recovery)) in the lipid and combination groups was significantly shorter than that in the epinephrine and control groups (P the lipid and epinephrine groups > the control group (P maximum)) and the ratio of RPP(maximum) to baseline value (RPP(maximum)/RPP(baseline)) from highest to lowest was the combination group > the lipid and epinephrine groups > the control group (P maximum), and RPP(maximum)/RPP(baseline). Cardiac tissue bupivacaine content in the epinephrine and control groups was higher than that in the lipid

  1. A Combined Antenna Arrays and Reverse-Link Synchronous DS-CDMA System over Frequency-Selective Fading Channels with Power Control Error

    Directory of Open Access Journals (Sweden)

    Yong-Seok Kim

    2004-08-01

    Full Text Available An improved antenna array (AA has been introduced, in which reverse-link synchronous transmission technique (RLSTT is incorporated to effectively make better an estimation of covariance matrices at a beamformer-RAKE receiver. While RLSTT is effective in the first finger at the RAKE receiver in order to reject multiple-access interference (MAI, the beamformer estimates the desired user's complex weights, enhancing its signal and reducing cochannel interference (CCI from the other directions. In this work, it is attempted to provide a comprehensive analysis of user capacity which reflects several important factors such as the shape of multipath intensity profile (MIP, the number of antennas, and power control error (PCE. Theoretical analysis, confirmed by the simulations, demonstrates that the orthogonality provided by employing RLSTT along with AA may make the DS-CDMA system insensitive to the PCE even with fewer numbers of antennas.

  2. Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID using zinc-finger nucleases.

    Directory of Open Access Journals (Sweden)

    Tomoji Mashimo

    Full Text Available BACKGROUND: Although the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES cells has been a major drawback for studies that aim to elucidate gene functions. Recently, zinc-finger nucleases (ZFNs were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc. METHODOLOGY/PRINCIPAL FINDINGS: We report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID. Co-injection of mRNAs encoding custom-designed ZFNs into the pronucleus of fertilized oocytes yielded genetically modified offspring at rates greater than 20%, which possessed a wide variety of deletion/insertion mutations. ZFN-modified founders faithfully transmitted their genetic changes to the next generation along with the severe combined immune deficiency phenotype. CONCLUSIONS AND SIGNIFICANCE: The efficient and rapid generation of gene knockout rats shows that using ZFN technology is a new strategy for creating gene-targeted rat models of human diseases. In addition, the X-SCID rats that were established in this study will be valuable in vivo tools for evaluating drug treatment or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies.

  3. THE SAFETY AND EFFICACY OF AMIODARONE AND CARVEDILOL COMBINATION IN TREATMENT OF PATIENTS WITH SEVERE CARDIAC RHYTHM DISORDERS.

    Science.gov (United States)

    Tsetskhladze, E; Khintibidze, I

    2017-06-01

    Different arrhythmias are cause of sudden death in many patients with heart failure. Amiodarone is usually used for prevent this arrhythmias, but it is not drug of choice for treatment the patients with heart failure. We retrospectively analyzed 142 patients with moderate and severe heart failure and history of myocardial infarction. These patients have received amiodarone, carvedilol or combination of these two medications together with standard therapy. In our retrospective analysis, the combination therapy with Amiodarone and Carvedilol had highly significant decrease arrhythmic death compare with carvedilol and amiodarone groups. This therapy is more effective in recovering of sinus rhythm in patients with atrial fibrillation and for control ventricular arrhythmias. The effects of carvedilol on left ventricular remodeling, systolic function and symptomatic status are not affected adversly by concurrent treatment with amiodarone. Carvedilol is an effective additional therapy for the patients with chronic heart failure already receiving Amiodarone. Carvedilol can be added to Amiodarone in patients with severe ventricular rhythm disorders and increased risk of sudden death without expecting of increase adverse events (than either drug alone) or loss of clinical efficacy.

  4. Pegademase bovine (PEG-ADA for the treatment of infants and children with severe combined immunodeficiency (SCID

    Directory of Open Access Journals (Sweden)

    Claire Booth

    2009-06-01

    Full Text Available Claire Booth1,2, H Bobby Gaspar1,21Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UK; 2Dept of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UKAbstract: Adenosine deaminase deficiency (ADA is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID, a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT with pegademase bovine (PEG-ADA and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.Keywords: adenosine deaminase deficiency, PEG-ADA, enzyme replacement therapy, severe combined immune deficiency (SCID

  5. Trauma-focused treatment for posttraumatic stress disorder combined with CBT for severe substance use disorder: a randomized controlled trial.

    Science.gov (United States)

    van Dam, Debora; Ehring, Thomas; Vedel, Ellen; Emmelkamp, Paul M G

    2013-06-19

    This randomized controlled trial (RCT) investigated the effectiveness of a combined treatment for co-morbid Posttraumatic Stress Disorder (PTSD) and severe Substance Use Disorder (SUD). Structured Writing Therapy for PTSD (SWT), an evidence-based traumafocused intervention, was added on to Treatment As Usual (TAU), consisting of an intensive cognitive behavioral inpatient or day group treatment for SUD. The outcomes of the combined treatment (TAU + SWT) were compared to TAU alone in a sample of 34 patients. Results showed a general reduction of SUD symptoms for both TAU + SWT and TAU. Treatment superiority of TAU + SWT was neither confirmed by interaction effects (time x condition) for SUD or PTSD symptoms, nor by a group difference for SUD diagnostic status at post-treatment. However, planned contrasts revealed that improvements for PTSD severity over time were only significant within the TAU + SWT group. In addition, within the TAU + SWT group the remission of PTSD diagnoses after treatment was significant, which was not the case for TAU. Finally, at post-treatment a trend was noticed for between group differences for the number of PTSD diagnoses favoring TAU + SWT above TAU. In sum, the current study provides preliminary evidence that adding a trauma-focused treatment on to standard SUD treatment may be beneficial.

  6. Conjunctival Flap Covering Combined with Antiviral and Steroid Therapy for Severe Herpes Simplex Virus Necrotizing Stromal Keratitis

    Directory of Open Access Journals (Sweden)

    Hua Gao

    2015-01-01

    Full Text Available Herpes simplex virus (HSV necrotizing stromal keratitis is a common type of herpetic stromal keratitis (HSK. Antiviral medication alone cannot control the disease, and corticosteroid eye drops may aggravate the ulcer and result in corneal perforation. Amniotic membrane transplantation effectively treats superficial corneal ulcer resulting from necrotizing stromal HSK. However, the efficacy of this approach seems to be limited for more serious cases. This study presented the clinical treatment of severe HSV necrotizing stromal keratitis (ulcer depth greater than half of the corneal stroma by conjunctival flap covering surgery in 25 patients (25 eyes combined with antivirus and corticosteroid treatment at Shandong Eye Hospital from January 2007 to December 2013. Clinical results showed that the mean best spectacle-corrected visual acuity improved from preoperative 20/333 to postoperative 20/40 (P<0.05. All patients recovered ocular surface stabilization. There was recurrence in two eyes, which was cured with antiviral medication. Conjunctival flap covering combined with antivirus and corticosteroid treatment is effective in treating severe HSV necrotizing stromal keratitis.

  7. The modified Cincinnati procedure: combined conjunctival limbal autografts and keratolimbal allografts for severe unilateral ocular surface failure.

    Science.gov (United States)

    Chan, Clara C; Biber, Joseph M; Holland, Edward J

    2012-11-01

    To describe the technique and present the outcomes of combined conjunctival limbal autografts (CLAU) and keratolimbal allografts (KLAL) for the treatment of unilateral severe ocular surface failure. Interventional case series. Eleven eyes of 11 patients who sustained chemical burns (4 alkali and 2 acid) and combined chemical/thermal burns (5 eyes) from firework explosions had combined CLAU/KLAL surgery. Keratoplasty was performed subsequently for residual corneal stromal scarring limiting visual acuity. Inclusion criteria included eyes with severe unilateral total ocular surface failure, controlled glaucoma, and reasonable eyelid apposition with no exposure. Exclusion criteria included patients with any ocular surface abnormality in the fellow eye and those with contraindications to systemic immunosuppression (SI). Outcome measures included Snellen best-corrected visual acuity (BCVA), ocular surface stability, SI exposure, and complications. Preoperative BCVA was 20/400 or worse in all eyes. At the final follow-up (mean, 35.8 months; range, 12.1-105.9 months), 73% (8 of 11) eyes had BCVA of 20/80 or better (range, 20/25 to counting fingers), and ocular surface was stable in 82% (9 of 11). Ninety-one percent (10 of 11) had additional penetrating keratoplasty (PK) with a 60% (6 of 10 eyes) success rate. Three cases had subsequent Boston type 1 keratoprosthesis implantation after PK failure, and the fourth patient, at the time of his last follow-up visit, did not want further intervention for his edematous PK, which was a result of noncompliance-related corneal rejection. In eyes with more than 2 years of follow-up, SI was tapered at a mean of 16 months (range, 8-28 months). There were no intraoperative complications. No secondary tumors, cardiac events, or deaths occurred while patients were on SI. One patient developed secondary glaucoma refractory to medical management after subsequent PK, requiring cyclodiode laser. Combined CLAU/KLAL and staged keratoplasty is

  8. Systematic neonatal screening for severe combined immunodeficiency and severe T-cell lymphopenia: Analysis of cost-effectiveness based on French real field data.

    Science.gov (United States)

    Clément, Marie Caroline; Mahlaoui, Nizar; Mignot, Cécile; Le Bihan, Christine; Rabetrano, Hasina; Hoang, Ly; Neven, Bénédicte; Moshous, Despina; Cavazzana, Marina; Blanche, Stéphane; Fischer, Alain; Audrain, Marie; Durand-Zaleski, Isabelle

    2015-06-01

    The inclusion of severe combined immunodeficiency (SCID) in a Europe-wide screening program is currently debated. In making a case for inclusion in the French newborn screening program, we explored the costs incurred and potentially saved by early management of SCID. For test costs, a microcosting study documented the resources used in a laboratory piloting a newborn screening test on Guthrie cards using the T-cell receptor excision circle quantification method. For treatment costs, patients with SCID admitted to the national reference center for primary immunodeficiency in France between 2006 and 2010 were included. Costs of admission were estimated from actual national production costs. We estimated the costs for patients who underwent early versus delayed hematopoietic stem cell transplantation (HSCT; age, ≤3 vs. >3 months, respectively). The unit cost of the test varied between €4.69 and €6.79 for 33,800 samples per year, depending on equipment use and saturation. Of the 30 patients included, 27 underwent HSCT after age 3 months. At 1 year after HSCT, 10 of these had died, and all 3 patients undergoing early transplantation survived. The medical costs for HSCT after 3 months were €195,776 (interquartile range, €165,884-€257,160) versus €86,179 (range, €59,014-€272,577) when performed before 3 months of age. In patients undergoing late transplantation, active infection contributed to high cost and poor outcome. Early detection of SCID could reduce the cost of treatment by €50,000-100,000 per case. Assuming a €5 unit cost per test, the incidence required to break even is 1:20,000; however, if the survival advantage of HSCT before 3 months is confirmed, universal screening is likely to be cost-effective. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Effects of several in-feed antibiotic combinations on the abundance and diversity of fecal microbes in weaned pigs.

    Science.gov (United States)

    Li, Huizhi; Liang, Tingting; Chu, Qingpo; Xu, Feilong; Li, Yuan; Fu, Lingling; Zhou, Bo

    2017-05-01

    To characterize the effects of several subtherapeutic antibiotic combinations on the abundance and diversity of fecal microbes, 400 weaned pigs were selected and randomly assigned to 8 groups, where they were continuously fed different antibiotic combinations for 28 days. Then, a total of 48 pigs were randomly selected to collect feces samples for DNA extraction and 16S rRNA high-throughput sequencing. Compared with that of pigs without antibiotic administration, the diversities of fecal microbes were decreased in the pigs fed chlortetracycline (CTC), olaquindox (OLA), and either enramycin (ER) or virginiamycin (VIR), and the relative abundances of members of the phylum Bacteroidetes and the genus Prevotella were increased. Compared with that of pigs without antibiotic administration, the relative abundances of members of the phylum Proteobacteria and the genus Succinivibrio were decreased in the pigs fed CTC, a mixture of zinc bacitracin (ZB) + colistin sulfate (COL), a mixture of CTC+ZB+COL, a mixture of CTC+OLA, or a mixture of CTC+OLA+ER. α-Diversity and β-diversity were decreased (P antibiotic combinations on intestinal microbes.

  10. Roflumilast combined with montelukast versus montelukast alone as add-on treatment in patients with moderate-to-severe asthma.

    Science.gov (United States)

    Bateman, Eric D; Goehring, Udo-Michael; Richard, Frank; Watz, Henrik

    2016-07-01

    Roflumilast, a selective phosphodiesterase 4 inhibitor, has been shown to provide modest improvements in lung function in patients with mild-to-moderate asthma, but its efficacy in patients with moderate-to-severe asthma has not been assessed. We hypothesized that this drug might provide benefit if combined with montelukast, a leukotriene receptor antagonist, in patients whose symptoms are uncontrolled by inhaled corticosteroids and long-acting β-agonists. We sought to examine the efficacy, safety, and mode of action of the addition of roflumilast and montelukast versus montelukast alone in patients with moderate-to-severe asthma. In a phase 2, randomized, double-blind, placebo-controlled, multiple-dose, 2-sequence, crossover study, 64 patients were randomized to receive 500 μg of roflumilast plus montelukast followed by placebo plus 10 mg of montelukast (sequence AB) or placebo plus 10 mg of montelukast followed by 500 μg of roflumilast plus 10 mg of montelukast (sequence BA). All patients had a diagnosis of bronchial asthma inadequately controlled by at least a medium-dose inhaled corticosteroid plus a long-acting β-agonist. The analysis of FEV1 change from baseline to week 4 showed a statistically significant and clinically meaningful treatment difference of 100 mL for roflumilast plus montelukast versus placebo plus montelukast. Also, improvements in patient-reported outcomes and a reduction in urinary leukotriene E4 levels were observed during roflumilast plus montelukast treatment compared with placebo plus montelukast treatment. Adverse events were consistent with the known safety profile of roflumilast. The combination of roflumilast with montelukast compared with montelukast alone improved lung function and asthma control in patients with moderate-to-severe asthma and deserves further study for this indication. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Short-term combination therapy and long-term relapse prevention in the treatment of severe acne vulgaris.

    Science.gov (United States)

    Tan, Jerry; Stein Gold, Linda; Schlessinger, Joel; Brodell, Robert; Jones, Terry; Cruz, Alma; Kerrouche, Nabil; Jarratt, Michael

    2012-02-01

    Few long-term treatment regimens for severe acne vulgaris have been investigated in clinical trials. Data were combined from two consecutive, randomized, double-blind, controlled studies to evaluate the efficacy, safety and subject satisfaction of four nine-month regimens in severe acne vulgaris treatment. Subjects were first randomized to receive doxycycline (DCN) and adapalene 0.1% - benzoyl peroxide 2.5% (A/BPO) or vehicle once daily for 12 weeks. Subjects who had at least 50% global improvement were subsequently randomized to receive A/BPO or its vehicle once daily for 24 weeks. Over nine months, there were four regimens: A/BPO and DCN followed by A/BPO, vehicle and DCN followed by A/BPO, A/BPO and DCN followed by vehicle, and vehicle and DCN followed by vehicle. Among the four regimens, A/BPO and DCN followed by A/BPO led to the highest percentage of subjects rated "clear" or "almost clear" (50.0% vs. 40.4%, 26.2% and 25.0%, respectively), biggest reduction in total lesion counts (76% vs. 70%, 51% and 47%, respectively) and greatest subject satisfaction (85.0% vs. 75.5%, 63.3% and 52.4%, respectively) at week 36. It provided a faster onset of action compared to groups started with vehicle and DCN (PBPO and DCN followed by vehicle experienced deterioration once the active treatment was discontinued. All regimens were safe and well-tolerated. In conclusion, efficacious initial therapy and long-term treatment are both important. An initial combination therapy with adapalene-BPO and DCN followed by longer-term adapalene-BPO treatment is an efficacious and satisfactory new regimen for severe acne subjects.

  12. Rapid and simple detection of Japanese encephalitis virus by reverse transcription loop-mediated isothermal amplification combined with a lateral flow dipstick.

    Science.gov (United States)

    Deng, Jieru; Pei, Jingjing; Gou, Hongchao; Ye, Zuodong; Liu, Cuicui; Chen, Jinding

    2015-03-01

    Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in geographical areas, such as Asia and Western Pacific, where it is a threat to human and animal health. To control this disease, it is necessary to develop a rapid, simple, accurate method for diagnosis. In this study, a method based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) coupled with a lateral flow dipstick (LFD) has been developed to detect JEV (JEV RT-LAMP-LFD). The entire assay can be completed within 70 min, and in this study, no false positive results were observed when other pathogens were tested, indicating that the assay is a highly specific method for the detection of JEV. Additionally, the sensitivity of the RT-LAMP-LFD assay for SA14-14-2 strain was 50 pg of RNA, which was similar to that of RT-PCR and RT-LAMP combined with gel electrophoresis, and was 10-fold more sensitive than RT-LAMP combined with calcein. The limit of detection for this assay was 5 pg of RNA. In addition, no false positive results were obtained with 14 serum samples. Our results indicate that this RT-LAMP-LFD assay will be of great value for JEV infection testing due to its rapid and highly specific and sensitive properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Reverse Logistics

    OpenAIRE

    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  14. Combination therapy with triamcinolone acetonide and bevacizumab for the treatment of severe radiation maculopathy in patients with posterior uveal melanoma

    Directory of Open Access Journals (Sweden)

    Shah NV

    2013-09-01

    Full Text Available Nisha V Shah,1 Samuel K Houston,1 Arnold Markoe,2 Timothy G Murray1,2,3 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA; 3Murray Ocular Oncology and Retina, Miami, FL, USA Purpose: To evaluate the role of intravitreal triamcinolone acetonide in patients who developed severe, visually compromising radiation maculopathy or progressed despite anti-angiogenic treatments. Methods: An Institutional Review Board approved, consecutive, retrospective study from 2006 to 2009 of patients who developed severe, visually compromising radiation retinopathy manifesting as macular edema secondary to iodine-125 plaque brachytherapy for posterior uveal melanoma, were treated with a combination of intravitreal bevacizumab and intravitreal triamcinolone. Patients were evaluated with spectral domain optical coherence tomography (SD-OCT at 2–4 month intervals following plaque removal. Treatment with intravitreal bevacizumab commenced at the first signs of visually compromising macular edema diagnosed with SD-OCT. Triamcinolone acetonide was administered to patients with severe maculopathy as consolidative therapy, or for patients that were refractory to repeated bevacizumab injections with persistent or worsening cystoid macular edema and lack of improvement or progressive worsening of best corrected visual acuity (BCVA. Results: Twenty-five patients were evaluated after receiving a combination of intravitreal bevacizumab and triamcinolone. Initial treatment commenced at a mean of 14.5 (range of 2–42 months after plaque brachytherapy. Patients were given a mean of two injections (range 1–6 of triamcinolone acetonide, and a mean of 8.8 bevacizumab injections (range of 1–26 with a mean follow-up of 31.2 months. Radiation maculopathy upon first detection had a mean SD-OCT grade of 3.6 (median

  15. Combination therapy with triamcinolone acetonide and bevacizumab for the treatment of severe radiation maculopathy in patients with posterior uveal melanoma.

    Science.gov (United States)

    Shah, Nisha V; Houston, Samuel K; Markoe, Arnold; Murray, Timothy G

    2013-01-01

    To evaluate the role of intravitreal triamcinolone acetonide in patients who developed severe, visually compromising radiation maculopathy or progressed despite anti-angiogenic treatments. An Institutional Review Board approved, consecutive, retrospective study from 2006 to 2009 of patients who developed severe, visually compromising radiation retinopathy manifesting as macular edema secondary to iodine-125 plaque brachytherapy for posterior uveal melanoma, were treated with a combination of intravitreal bevacizumab and intravitreal triamcinolone. Patients were evaluated with spectral domain optical coherence tomography (SD-OCT) at 2-4 month intervals following plaque removal. Treatment with intravitreal bevacizumab commenced at the first signs of visually compromising macular edema diagnosed with SD-OCT. Triamcinolone acetonide was administered to patients with severe maculopathy as consolidative therapy, or for patients that were refractory to repeated bevacizumab injections with persistent or worsening cystoid macular edema and lack of improvement or progressive worsening of best corrected visual acuity (BCVA). Twenty-five patients were evaluated after receiving a combination of intravitreal bevacizumab and triamcinolone. Initial treatment commenced at a mean of 14.5 (range of 2-42) months after plaque brachytherapy. Patients were given a mean of two injections (range 1-6) of triamcinolone acetonide, and a mean of 8.8 bevacizumab injections (range of 1-26) with a mean follow-up of 31.2 months. Radiation maculopathy upon first detection had a mean SD-OCT grade of 3.6 (median = 4), with an associated mean entry level BCVA of 20/70. Visual acuity at time of first intravitreal triamcinolone was 20/138. At last follow-up (mean of 45.5 months after plaque brachytherapy) mean BCVA was 20/136; however, 9 of 25 (36%) patients who presented with severe radiation maculopathy demonstrated 20/50 or better vision at last follow-up. This case series suggests a beneficial role

  16. Successful desensitization in a boy with severe cow's milk allergy by a combination therapy using omalizumab and rush oral immunotherapy.

    Science.gov (United States)

    Takahashi, Masaya; Taniuchi, Shoichiro; Soejima, Kazuhiko; Hatano, Yasuko; Yamanouchi, Sohsaku; Kaneko, Kazunari

    2015-01-01

    Rush oral immunotherapy (OIT) combined with omalizumab (OMB) has been reported to be an effective and safe treatment for severe milk allergies. However, no report has described long-term follow-up observations after OMB discontinuation. The purpose of this case report was to evaluate the safety and efficacy of rush OIT in combination with OMB during a long period of treatment. A 5-year-old boy presented with a past history of two severe episodes of anaphylaxis (at the age of 2 and 3 years) after consuming small amounts of cow's milk (CM). Before the OIT, the total immunoglobulin E (IgE) level was 654 IU/mL, and specific-IgE (sIgE) levels for CM, casein, and β-lactoglobulin were 77.0 kUA/L, 86.2 kUA/L and 12.0 kUA/L, respectively. The skin prick test (SPT) for CM showed a wheal (diameter, 20 mm) and erythema (diameter, 50 mm). In the open food challenge, he reacted to a 0.2 mL ingestion of CM and presented with dyspnea and laryngospasms, and he was then administrated 150 mg OMB every 2 weeks for 8 weeks. In the 9th week, he was admitted to hospital for the rush phase of the OIT. Once he was able ingest a dose of 200 mL CM without having an adverse reaction, he was discharged and allowed to continue a daily dose of 200 mL CM at home. During this phase, the sIgE levels were elevated, but the end-point titration values from the SPT gradually decreased, and the SPT was negative after 1 year of OMB treatment. Five months after discontinuation of OMB, the daily CM ingestion was ceased for a 2-week period, followed by an oral food challenge (OFC) that was negative. The patient experienced only five mild adverse events during the course of rush OIT, even after the discontinuation of OMB and his quality of life improved dramatically afterwards. The combination therapy of rush OIT and OMB successfully maintained desensitization to CM in a boy with severe allergies. We propose that a negative SPT may be useful to guide discontinuation of OMB in such patients.

  17. For Single Dosing, Levofloxacin Is Superior to Ciprofloxacin When Combined With an Aminoglycoside in Preventing Severe Infections After Prostate Biopsy.

    Science.gov (United States)

    Unnikrishnan, Raman; El-Shafei, Ahmed; Klein, Eric A; Jones, J Stephen; Kartha, Ganesh; Goldman, Howard B

    2015-06-01

    To investigate whether there is benefit with a longer acting oral fluoroquinolone, we compared the rate of infection after transrectal ultrasound-guided prostate biopsy between 2 prophylactic antibiotic regimens: ciprofloxacin vs levofloxacin, each combined with an aminoglycoside (AG). A retrospective review was performed of all transrectal ultrasound-guided prostate biopsies from September 2011 to January 2013. Initially our regimen entailed 1 dose of 500-mg ciprofloxacin and an AG. In June 2012, we switched to 1 dose of 750-mg levofloxacin and an AG. Infections were categorized as severe if requiring hospital admission, overnight observation, or emergency room treatment for fever or chills. Those treated as an outpatient were defined as mild. Of 1189 total biopsies, the total infection rate was 3.18% (17 of 535) in the ciprofloxacin group and 2.14% (14 of 654) in the levofloxacin group (P = .26). The rate of mild infection was 0.75% (4 of 535) in the ciprofloxacin group and 1.22% (8 of 654) in the levofloxacin group (P = .56). The rate of severe infection was significantly higher in the ciprofloxacin group at 2.43% (13 of 535) compared with that of 0.92% (6 of 654) in the levofloxacin group (P = .04). On multivariate analysis, use of ciprofloxacin rather than levofloxacin was associated with an increased risk of severe infection (odds ratio, 4.59; P = .04). Empiric prophylaxis for prostate biopsies with a single-dose fluoroquinolone augmented with an AG is optimal to reduce infectious complications. We found 750-mg levofloxacin resulted in significantly fewer severe infections compared with 500-mg ciprofloxacin potentially because of its longer half-life. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside

    Directory of Open Access Journals (Sweden)

    Smriti Kundu-Raychaudhuri

    2014-01-01

    Full Text Available Psoriasis is a multifactorial chronic inflammatory disease. Research into the pathogenesis of this disease is hindered by the lack of a proper animal model. Over the past two decades, many scientists were involved in the development of animal models that nearly mirror the immunopathogenesis of psoriasis. One such model, which has opened doors to the study of molecular complexities of psoriasis as well as its treatment, is the severe combined immunodeficiency (SCID mouse-human skin chimera model. This model not only mirrors the clinical and histopathological features of psoriasis but also help in the study of cell proliferation, angiogenesis, function of T cells, neurogenic inflammation and cytokines involved in inflammatory reactions. In this article, we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

  19. Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency

    Directory of Open Access Journals (Sweden)

    B.E. Strauss

    2007-05-01

    Full Text Available A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.

  20. Strategies for B-cell receptor repertoire analysis in Primary Immunodeficiencies:From severe combined immunodeficiency to common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Hanna eIJspeert

    2015-04-01

    Full Text Available The antigen receptor repertoires of B and T cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective we describe strategies and considerations for analysis of the naive and antigen selected B-cell repertoires in primary immunodeficiency (PID patients with a focus on severe combined immunodeficiency (SCID and common variable immunodeficiency (CVID.

  1. Control of equine infectious anemia virus replication following immune reconstitution in an Arabian foal with severe combined immunodeficiency

    Science.gov (United States)

    Mealey, Robert H.; Fraser, Darrilyn G.; Oaks, J. Lindsay; Cantor, Glenn H.; McGuire, Travis C.

    2012-01-01

    Acute infection with equine infectious anemia virus (EIAV), a lentivirus of horses, results in a persistent high-level viremia in Arabian foals affected with severe combined immunodeficiency (SCID). This observation argues against the idea that the transient nature of acute lentiviral viremia is solely a function of viral population dynamics. To extend these studies, EIAV-specific immune reconstitution was attempted prior to EIAV challenge in 2 SCID foals, using adoptively transferred virus-stimulated lymphocytes derived from persistently EIAV-infected half sibling donors. Following transfer, lymphocyte engraftment occurred in 1 foal, and EIAV-specific cytotoxic T lymphocytes as well as neutralizing antibody activity developed. Following a brief period of plasma viremia in this foal, EIAV replication was controlled and plasma virus could not be detected by RT-PCR or culture. These results provide further direct evidence that a specific immune response is required for termination of plasma viremia in acute lentiviral infections. PMID:11683583

  2. A dual-mode human computer interface combining speech and tongue motion for people with severe disabilities.

    Science.gov (United States)

    Huo, Xueliang; Park, Hangue; Kim, Jeonghee; Ghovanloo, Maysam

    2013-11-01

    We are presenting a new wireless and wearable human computer interface called the dual-mode Tongue Drive System (dTDS), which is designed to allow people with severe disabilities to use computers more effectively with increased speed, flexibility, usability, and independence through their tongue motion and speech. The dTDS detects users' tongue motion using a magnetic tracer and an array of magnetic sensors embedded in a compact and ergonomic wireless headset. It also captures the users' voice wirelessly using a small microphone embedded in the same headset. Preliminary evaluation results based on 14 able-bodied subjects and three individuals with high level spinal cord injuries at level C3-C5 indicated that the dTDS headset, combined with a commercially available speech recognition (SR) software, can provide end users with significantly higher performance than either unimodal forms based on the tongue motion or speech alone, particularly in completing tasks that require both pointing and text entry.

  3. Intravitreal ranibizumab as a primary or a combined treatment for severe retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Arámbulo O

    2015-10-01

    Full Text Available Odalis Arámbulo,1 Gabriel Dib,1 Juan Iturralde,1 Fahir Duran,1 Miguel Brito,1 João B Fortes Filho2 1Department of Ophthalmology, University Hospital of Maracaibo, Maracaibo, Venezuela; 2Department of Ophthalmology, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil Purpose: The aim of the study was to assess the outcomes of severe retinopathy of prematurity (ROP in zone I or posterior zone II treated with intravitreal ranibizumab (IVR as monotherapy or combined treatment with laser photocoagulation.Methods: This is a retrospective study analyzing clinical records of the included patients. Patients were divided into two groups: group 1 included patients who received only IVR treatment; and group 2 was subdivided into group 2A – including patients with IVR as initial treatment and complementary laser photocoagulation if retinal neovascularization or plus disease did not regress, and group 2B – including patients with initial laser photocoagulation and IVR as rescue therapy. Favorable outcomes were regression of the retinal neovascularization and plus disease, meaning control of the disease. Unfavorable outcomes were progression to stages 4 and 5 of ROP.Results: Fifty-seven eyes were included in the study. Mean birth weight and gestational age were 1,281±254 g and 29.5±2.1 weeks, respectively. Group 1 comprised of 16 eyes, with favorable outcomes in 14 eyes (87.5%. Group 2 comprised of 41 eyes, with favorable outcomes in 29 eyes (70.7%, in a mean follow-up period of 12.8 months.Conclusion: IVR was effective to treat severe cases of ROP as a primary or a combined treatment. Forty-three of the 57 treated eyes (75.4% achieved regression of ROP and favorable outcomes. Keywords: aggressive posterior ROP, bevacizumab, prematurity, ranibizumab, retinopathy of prematurity, therapy, treatment, VEGF

  4. Combined Use of Rituximab and Intravenous Immunoglobulin for Severe Autoimmune Cicatricial Conjunctivitis-An Interventional Case Series.

    Science.gov (United States)

    Steger, Bernhard; Madhusudan, Savitha; Kaye, Stephen B; Stylianides, Amira; Romano, Vito; Maqsood, Sundas E; Harper, Janice; Ahmad, Sajjad

    2016-12-01

    Despite the availability of systemic immunosuppressants, cicatricial conjunctivitis (CC) remains a potentially blinding ocular surface disease. We aim to describe the combined use of rituximab (RTX) and intravenous immunoglobulin (IVIg) for severe recalcitrant autoimmune CC. In this single-center retrospective interventional case series with follow-up between 32 and 65 months, 3 cases with mucous membrane pemphigoid (patients 1-3) and 1 case with linear IgA disease (patient 4) were included. Initial conventional immunosuppressive therapy regimens included systemic steroids, dapsone, and mycophenolate. At the time of initiation of RTX and IVIg, all patients had only one eye with good visual acuity or good visual potential. Treatment included 1 to 2 cycles of RTX (1000 mg twice at an interval of 2 weeks apart), and 2 to 9 monthly courses of IVIg (2 g/kg over 3 days). Outcome measures were blindness, as defined by best spectacle-corrected visual acuity <0.05 on a decimal scale, and clinical staging of cicatricial disease (Rowsey and Foster staging). In 4 presented cases, progression of cicatricial disease was stopped as assessed by the Foster grading scale and visual acuity was stabilized in all patients. Conjunctival scarring was stabilized in 2 cases and continued to progress in 2 cases. One patient developed septicemia 6 weeks after RTX infusion, which was successfully treated. Combination therapy of RTX and IVIg is a potent treatment regimen for recalcitrant autoimmune CC. Further prospective controlled studies on efficacy and safety are warranted before widespread clinical application.

  5. A rare case of coinheritance of Hemoglobin H disease and sickle cell trait combined with severe iron deficiency

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2011-12-01

    Full Text Available We present a case of a 40-year-old female from Turkey, who was referred to our outpatient clinic for an undetermined thalassemia and sickle cell trait. At first consultation hemoglobin was decreased (71 g/L with microcytosis (MCV 55.1 fL, and hypochromia (MCHC 239 g/L. The patient had severe iron deficiency. Brilliant cresyl blue staining showed >50% of the erythrocytes with typical Hemoglobin H (HbH inclusions. High-performance liquid chromatography (HPLC revealed normal levels of HbA2 and Hemoglobin F (HbF, and additionally a hemoglobin S (19%. Molecular diagnostics revealed the mutations α2 IVS-I donor site -5nt and a -- MED II deletion in the alpha gene complex and confirmed the heterozygote mutation of the beta-gene at codon 6 (HBB:c.20A>T; HbS. In conclusion, we present an extremely rare combination of HbH disease and sickle cell trait. This combination may explain the mild form of the HbH disease, with moderate anemia, splenomegaly but iron deficiency, rather than iron overload, as usually observed in HbH disease.

  6. Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG)

    Energy Technology Data Exchange (ETDEWEB)

    Anker, Christopher J., E-mail: chris.anker@UVMHealth.org [Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, Vermont (United States); Grossmann, Kenneth F. [Division of Medical Oncology, Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (United States); Atkins, Michael B. [Department of Oncology, Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia (United States); Suneja, Gita [Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (United States); Tarhini, Ahmad A.; Kirkwood, John M. [Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States)

    2016-06-01

    BRAF kinase gene V600 point mutations drive approximately 40% to 50% of all melanomas, and BRAF inhibitors (BRAFi) have been found to significantly improve survival outcomes. Although radiation therapy (RT) provides effective symptom palliation, there is a lack of toxicity and efficacy data when RT is combined with BRAFi, including vemurafenib and dabrafenib. This literature review provides a detailed analysis of potential increased dermatologic, pulmonary, neurologic, hepatic, esophageal, and bowel toxicity from the combination of BRAFi and RT for melanoma patients described in 27 publications. Despite 7 publications noting potential intracranial neurotoxicity, the rates of radionecrosis and hemorrhage from whole brain RT (WBRT), stereotactic radiosurgery (SRS), or both do not appear increased with concurrent or sequential administration of BRAFis. Almost all grade 3 dermatitis reactions occurred when RT and BRAFi were administered concurrently. Painful, disfiguring nondermatitis cutaneous reactions have been described from concurrent or sequential RT and BRAFi administration, which improved with topical steroids and time. Visceral toxicity has been reported with RT and BRAFi, with deaths possibly related to bowel perforation and liver hemorrhage. Increased severity of radiation pneumonitis with BRAFi is rare, but more concerning was a potentially related fatal pulmonary hemorrhage. Conversely, encouraging reports have described patients with leptomeningeal spread and unresectable lymphadenopathy rendered disease free from combined RT and BRAFi. Based on our review, the authors recommend holding RT ≥3 days before and after fractionated RT and ≥1 day before and after SRS. No fatal reactions have been described with a dose <4 Gy per fraction, and time off systemic treatment should be minimized. Future prospective data will serve to refine these recommendations.

  7. Severity of lung fibrosis affects early surgical outcomes of lung cancer among patients with combined pulmonary fibrosis and emphysema.

    Science.gov (United States)

    Mimae, Takahiro; Suzuki, Kenji; Tsuboi, Masahiro; Ikeda, Norihiko; Takamochi, Kazuya; Aokage, Keiju; Shimada, Yoshihisa; Miyata, Yoshihiro; Okada, Morihito

    2016-07-01

    Combined pulmonary fibrosis and emphysema (CPFE) is defined as upper lobe emphysema and lower lobe fibrosis, which are representative lung disorders that increase the prevalence of lung cancer. This unique disorder may affect the morbidity and mortality during the early period after surgery. The present study aimed to identify which clinicopathological features significantly affect early surgical outcomes after lung resection in nonsmall cell lung cancer (NSCLC) patients and in those with CPFE.We retrospectively assessed 2295 patients with NSCLC and found that 151 (6.6%) had CPFE. All were surgically treated between January 2008 and December 2010 at 4 institutions.The postoperative complication rates for patients with and without CPFE were 39% and 17%, respectively. The 90-day mortality rates were higher among patients with than without CPFE (7.9% vs 1%). Acute exacerbation of interstitial pneumonia was the main cause of death among 12 patients with CPFE who died within 90 days after surgery. Multivariate logistic regression analysis selected CPFE, gender, age, and clinical stage as independent predictive factors for postoperative complications, and CPFE, clinical stage, and sex for 90-day mortality. The severity of lung fibrosis on preoperative CT images was an independent predictive factor for 90-day mortality among patients with CPFE.The key predictive factor for postoperative mortality and complications of lung resection for NSCLC was CPFE. The severity of lung fibrosis was the principal predictor of early outcomes after lung surgery among patients with CPFE and NSCLC.

  8. Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering".

    Science.gov (United States)

    Liu, Mengjin; Bienfait, Bruno; Sacher, Oliver; Gasteiger, Johann; Siezen, Roland J; Nauta, Arjen; Geurts, Jan M W

    2014-01-01

    The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.

  9. Sensitive determination of neurotransmitters in urine by microchip electrophoresis with multiple-concentration approaches combining field-amplified and reversed-field stacking.

    Science.gov (United States)

    Zhang, Yan; Zhang, Yi; Wang, Guan; Chen, Wujuan; Li, Yi; Zhang, Yating; He, Pingang; Wang, Qingjiang

    2016-07-01

    Microchip electrophoresis (MCE) is particularly attractive as it provides high sensitivity and selectivity, short analysis time and low sample consumption. An on-line preconcentration strategy combining field-amplified stacking (FASS) and reversed-field stacking (RFS) was developed for efficient and sensitive analysis of neurotransmitters in real urine samples by MCE with laser induced fluorescence (LIF) detection. In this study, the multiple-preconcentration strategy greatly improves the sensitivity enhancement and surpass other conventional analytical methods for neurotransmitters detection. Under optimal conditions, the separation of three neurotransmitters (dopamine, norepinephrine and serotonin), was achieved within 3min with limits of detection (S/N=3) of 1.69, 2.35, and 2.73nM, respectively. The detection sensitivities were improved by 201-, 182-, and 292-fold enhancement, for the three neurotransmitters respectively. Other evaluation parameters such as linear correlation coefficients were considered as satisfactory. A real urine sample was analyzed with recoveries of 101.8-106.4%. The proposed FASS-RFS-MCE method was characterized in terms of precision, linearity, accuracy and successfully applied for rapid and sensitive determination of three neurotransmitters in human urine. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The role of a combined coagulation and disk filtration process as a pre-treatment to microfiltration and reverse osmosis membranes in a municipal wastewater pilot plant.

    Science.gov (United States)

    Chon, Kangmin; Cho, Jaeweon; Kim, Seung Joon; Jang, Am

    2014-12-01

    A pilot study was conducted to assess the performance of a municipal wastewater reclamation plant consisting of a combined coagulation-disk filtration (CC-DF) process, microfiltration (MF) and reverse osmosis (RO) membranes, in terms of the removal of water contaminants and changes in characteristics of effluent organic matter (EfOM). The CC-DF and MF membranes were not effective for the removal of dissolved water contaminants. However, they could partially reduce the turbidity associated with the cake layer formation by particulate materials on the membrane surfaces. Furthermore, most of water contaminants were completely removed by the RO membranes. Although the CC-DF process could remove approximately 20% of turbidity, the aluminium concentrations considerably increased after the CC-DF process due to the residual coagulants complexed with both carboxylic acid and alcohol functional groups of EfOM. Those aluminium-EfOM complexes had a lower negative charge and higher molecular weight (>0.1 μm pore size of the MF membranes) compared to non-complexed EfOM. These results indicate that the control of the formation of the aluminium-EfOM complexes should be considered as a key step to use the CC-DF process as a pre-treatment of the MF and RO membranes for mitigation of membrane fouling in the tested pilot plant. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering".

    Directory of Open Access Journals (Sweden)

    Mengjin Liu

    Full Text Available The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE, which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.

  12. Stability-indicating reversed-phase liquid chromatographic method for simultaneous determination of atorvastatin and ezetimibe from their combination drug products.

    Science.gov (United States)

    Chaudhari, Bharat G; Patel, Natvarlal M; Shah, Paresh B; Patel, Laxman J; Patel, Vipul P

    2007-01-01

    A simple, precise, and rapid stability-indicating reversed-phase column liquid chromatographic (RP-LC) method has been developed and subsequently validated for simultaneous estimation of atorvastatin (ATV) and ezetimibe (EZE) from their combination drug product. The proposed RP-LC method utilizes a LiChrospher 100 C18, 5 microm, 250 x 4.0 mm id column at ambient temperature; the optimum mobile phase consists of acetonitrile-water-methanol (45 + 40 + 15, v/v/v) with apparent pH adjusted to 4.0 +/- 0.1; mobile phase flow rate of 1.0 mL/min; and UV detection at 250 nm. ATV, EZE, and their combination drug product were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. There were no other coeluting, interfering peaks from excipients, impurities, or degradation products due to variable stress conditions, and the method is specific for the estimation of ATV and EZE in the presence of degradation products. The response was linear over the concentration range of 1-80 microg/mL for ATV and EZE. The mean recoveries were 99.27 and 98.5% for ATV and EZE, respectively. The intermediate precision data were obtained under different experimental conditions, and the calculated value of the coefficient of variation was found to be less than the critical value. The proposed method can be useful in the quality control of bulk manufacturing and pharmaceutical dosage forms.

  13. Severe neuro-Behcet’s disease treated with a combination of immunosuppressives and a TNF-inhibitor.

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    Fatma Nur Korkmaz

    2016-10-01

    Full Text Available Abstract/ Resumo Behcet's disease (BD is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD, is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day, iv cylophosphamide (1g and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in

  14. [Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation].

    Science.gov (United States)

    Liu, Chang-Qing; Qin, Zi-Xin; Jiang, Fang-Fang; Hong, Ting; Wang, Feng

    2014-11-01

    To observe the effect of Kuntai Capsule (KC), a Chinese patent medicine, in add-back therapy for gonadotropin-releasing hormone agonist (GnRH-a) treatment for moderate-severe endometriosis (EM). Totally 100 patients suffering from stage III/IV EM, who were confirmed by laparoscopic surgery were randomly assigned to the GnRH-a group (A) and the KC combined GnRH-a group (B), 50 in each group. Patients in Group A were hypodermically injected with goserelin (3.6 mg), once per 4 weeks. Those in Group B additionally took KC, 4 pills each time, three times per day. The therapeutic course for all was 12 weeks. Serum levels of estradiol (E2), follicle stimulating hormone (FSH), bone gamma-carboxyglutamic-acid-containing proteins (BGP) were measured respectively. Kupperman Menopausal Index (KMI) and bone mineral density (BMD) of the lumbar vertebra were also compared between the two groups. Serum levels of E2 and FSH both significantly decreased in the two groups at week 12 of the treatment (P KMI increased in the two groups (P 0.05). Serum BGP increased after 12-week treatment (P KMI between the two groups (P > 0.05). As for the incidence of menopausal symptoms, better effects in improving symptoms such as hot flashes, sleep disorders, and vaginal dryness were obtained in Group B than in Group A (P < 0.05). There was no significant difference in the post-pre-treatment difference of BMI between the two groups, but with statistical post-pre-treatment difference in the BGP level (P < 0.05). HKC combined GnRH-a could effectively reduce GnRH-a treatment induced partial low estrogen symptoms, improve increased serum BGP levels after GnRH-a therapy.

  15. Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

    Directory of Open Access Journals (Sweden)

    Lukashevich V

    2013-01-01

    Full Text Available Valentina Lukashevich,1 Anja Schweizer,2 James E Foley,1 Sheila Dickinson,2 Per-Henrik Groop,3 Wolfgang Kothny11Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Pharma AG, Basel, Switzerland; 3Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Finland, and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, AustraliaBackground: The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2 and longstanding type 2 diabetes not adequately controlled with insulin therapy, which is a difficult-to-treat population, with limited therapeutic options and a high susceptibility to hypoglycemia.Methods: This was a post hoc subanalysis of data obtained during a previously described randomized, double-blind, parallel-group, 24-week study comparing the efficacy and safety of vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m2, 100 randomized to vildagliptin, 78 randomized to placebo, all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent for longstanding type 2 diabetes (mean approximately 19 years.Results: With vildagliptin in combination with insulin, the adjusted mean change (AMΔ in HbA1c from baseline (7.7% ± 0.1% was -0.9% ± 0.4% and the between-treatment difference (vildagliptin – placebo was -0.6% ± 0.2% (P < 0.001. The percentage of patients achieving endpoint HbA1c < 7.0% was significantly higher with vildagliptin than placebo (45.2% versus 22.8%, P = 0.008. When added to insulin, vildagliptin and placebo had

  16. The effectiveness of Nigella sativa, methotrexate and their combination in the treatment of moderate to severe psoriasis

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    Jawad Hassan Ahmed

    2014-12-01

    Full Text Available Objective: Methotrexate (MTX is a commonly prescribed drug for patients with psoriasis. Nigella sativa (NS has been shown beneficial in vitiligo and in eczema. Recently, NS has shown activity in modifying psoriatic lesions. The aim of this study was to evaluate the effect of the combination (NS+MTX on psoriasis and to compare that with NS or MTX monotherapy. Methods: Sixty patients with moderate to severe plaque, palmoplantar and guttate psoriasis were enrolled for 12 weeks study. The patients were divided into 3 groups; 20 patients in each. Group 1 was treated with NS ointment (20% w/w 2 times daily + 500 mg NS capsule 3 times daily. Group 2 received MTX tablets 15 mg weekly and group 3 received MTX + NS (topical + oral. Results: Marked response was achieved in 60%, 80%, and 90% of patients on NS, MTX, and (NS + MTX respectively. The respective relapse rate was 33.3%, 56.3%, and 27.8%. Serum malondialdehyde (sMDA, a parameter of oxidative stress was decreased from 4.39 ± 0.81 to 2.31 ± 0.72 µmol/L with NS treatment while a small increase in sMDA was observed with MTX. NS + MTX treatment reduced sMDA from 4.39 ± 0.67 to 3.49 ± 0.65 µmol/L after 12 weeks treatment. All treatments did not change liver enzymes or complete blood count. NS was well tolerated and showed ability in ameliorating gastric upset of MTX. Conclusion: NS augments antipsoriatic effect of MTX. Topical and oral use of NS is effective and safe in moderate to severe psoriasis. J Clin Exp Invest 2014; 5 (4: 521-528

  17. Endodontic and periodontal management of a severely affected maxillary lateral incisor having combined mucosal fenestration and palatogingival groove.

    Science.gov (United States)

    Sharma, Sarang; Srivastava, Dhirendra; Sood, Vishal; Yadav, Priya

    2015-01-01

    Mucosal fenestrations, wherein the tooth root apices are clinically discernible in the oral cavity subsequent to loss of overlying alveolar bone and mucosa, are rare pathologic entities. Palato gingival grooves- anatomic aberrations are also infrequent occurrences that notoriously predispose to periodontal pathologies of varying extent. Both conditions independently are known to popularly affect maxillary lateral incisors. Coexistent fenestration defect and palato gingival groove in the same tooth is extremely rare and undoubtedly is a perfect combination to precipitate severe endodontic-periodontal consequences. In this report, a 34-year-old patient presented to the dental department with complaint of esthetics in relation to exposed root of right maxillary lateral incisor. On closer inspection, a palato gingival groove in addition to fenestration defect was evident on the root surface along with a periodontal pocket of >5 mm. An interdisciplinary treatment was instituted which included endodontic treatment followed by root end resection, osseous bone graft placement and guided tissue regeneration procedures for repair of mucosal fenestration defect. Debridement of the palatal pocket, with saucerization of the groove and restoration with glass ionomer cement were simultaneously employed to correct the palatal defect.

  18. Correction of moderate to severe hallux valgus with combined proximal opening wedge and distal chevron osteotomies: a reliable technique.

    Science.gov (United States)

    Jeyaseelan, L; Chandrashekar, S; Mulligan, A; Bosman, H A; Watson, A J S

    2016-09-01

    The mainstay of surgical correction of hallux valgus is first metatarsal osteotomy, either proximally or distally. We present a technique of combining a distal chevron osteotomy with a proximal opening wedge osteotomy, for the correction of moderate to severe hallux valgus. We reviewed 45 patients (49 feet) who had undergone double osteotomy. Outcome was assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) and the Short Form (SF) -36 Health Survey scores. Radiological measurements were undertaken to assess the correction. The mean age of the patients was 60.8 years (44.2 to 75.3). The mean follow-up was 35.4 months (24 to 51). The mean AOFAS score improved from 54.7 to 92.3 (p technique which, when compared with other metatarsal osteotomies, provides strong angular correction and excellent outcomes with a low rate of complications. Cite this article: Bone Joint J 2016;98-B:1202-7. ©2016 The British Editorial Society of Bone & Joint Surgery.

  19. Endodontic and periodontal management of a severely affected maxillary lateral incisor having combined mucosal fenestration and palatogingival groove

    Directory of Open Access Journals (Sweden)

    Sarang Sharma

    2015-01-01

    Full Text Available Mucosal fenestrations, wherein the tooth root apices are clinically discernible in the oral cavity subsequent to loss of overlying alveolar bone and mucosa, are rare pathologic entities. Palato gingival grooves- anatomic aberrations are also infrequent occurrences that notoriously predispose to periodontal pathologies of varying extent. Both conditions independently are known to popularly affect maxillary lateral incisors. Coexistent fenestration defect and palato gingival groove in the same tooth is extremely rare and undoubtedly is a perfect combination to precipitate severe endodontic-periodontal consequences. In this report, a 34-year-old patient presented to the dental department with complaint of esthetics in relation to exposed root of right maxillary lateral incisor. On closer inspection, a palato gingival groove in addition to fenestration defect was evident on the root surface along with a periodontal pocket of >5 mm. An interdisciplinary treatment was instituted which included endodontic treatment followed by root end resection, osseous bone graft placement and guided tissue regeneration procedures for repair of mucosal fenestration defect. Debridement of the palatal pocket, with saucerization of the groove and restoration with glass ionomer cement were simultaneously employed to correct the palatal defect.

  20. T Cell Lymphoma and Leukemia in Severe Combined Immunodeficiency Pigs following Bone Marrow Transplantation: A Case Report

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    Ellis J. Powell

    2017-07-01

    Full Text Available After the discovery of naturally occurring severe combined immunodeficiency (SCID within a selection line of pigs at Iowa State University, we found two causative mutations in the Artemis gene: haplotype 12 (ART12 and haplotype 16 (ART16. Bone marrow transplants (BMTs were performed to create genetically SCID and phenotypically immunocompetent breeding animals to establish a SCID colony for further characterization and research utilization. Of nine original BMT transfer recipients, only four achieved successful engraftment. At approximately 11 months of age, both animals homozygous for the ART16 mutation were diagnosed with T cell lymphoma. One of these ART16/ART16 recipients was a male who received a transplant from a female sibling; the tumors in this recipient consist primarily of Y chromosome-positive cells. The other ART16/ART16 animal also presented with leukemia in addition to T cell lymphoma, while one of the ART12/ART16 compound heterozygote recipients presented with a nephroblastoma at a similar age. Human Artemis SCID patients have reported cases of lymphoma associated with a “leaky” Artemis phenotype. The naturally occurring Artemis SCID pig offers a large animal model more similar to human SCID patients and may offer a naturally occurring cancer model and provides a valuable platform for therapy development.

  1. Recombination activating gene-2null severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently

    Science.gov (United States)

    Choi, Yun-Jung; Kim, EunSu; Reza, Abu Musa Md Talimur; Hong, Kwonho; Song, Hyuk; Park, Chankyu; Cho, Seong-Keun; Lee, Kiho; Prather, Randall S.; Kim, Jin-Hoi

    2017-01-01

    This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3+-, CD4+-, and CD8+ signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFATC1, CD79B, CD2, BLNK, FOXO1, and CD40) was more downregulated than that in the Rag-2 SCID mice, which provides a partial rationale for the death of T/B cells in the lymphoid organs of RAG-2 SCID pigs but not in Rag-2 SCID mice. Further, NK cell maturation-related gene expression was significantly lower in RAG-2 SCID pigs than in Rag-2 SCID mice. Consistently, the RAG-2 SCID pigs, but not Rag-2 SCID mice, developed human induced pluripotent stem cell-derived teratomas that were the same as those of perforin/Rag-2 SCID mice. Therefore, these unexpected findings indicate the superiority of RAG-2 SCID pigs over Rag-2 SCID mice as a suitable model for investigating human diseases. PMID:29050212

  2. Two mutational hotspots in the interleukin-2 receptor {gamma} chain gene causing human X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, A.E.; Puck, J.M. [National Institutes of Health, Bethesda, MD (United States); Buckley, R.H. [and others

    1995-09-01

    Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor {gamma} chain (IL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute >20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations. 41 refs., 5 figs., 1 tab.

  3. Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Deschenes, S.M.; Puck, J.M.; Dutra, A.S. [Univ. of Pennsylvania School of Medicine and Children`s Hospital of Philadelphia, PA (United States)] [and others

    1994-09-01

    Parallel genetic analysis of animal and human genetic diseases can facilitate the identification and characterization of the causative gene defects. For example, canine X-linked severe combined immunodeficiency (SCID) is characterized by clinical, pathological, and immunological manifestations similar to the most common form of human SCID. To derive a canine syntenic map including genes that in humans are located in proximal Xq, near human X-linked SCID, poly (TG) polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and choroideremia (CHM) loci. These plus a polymorphic poly (CAG) sequence in exon 1 of the canine androgen receptor gene (AR) were used to genotype members of the colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to proximal Xq in the dog, in the same chromosomal location occupied by the human genes. Somatic cell hybrid analysis and methylation differences at AR demonstrated that female dogs carrying X-linked SCID have the same lymphocyte-limited skewed X-chromosome inactivation patterns as human carriers. These genetic and phenotypic findings provide evidence that mutations in the same gene, now identified as the {gamma} chain of the IL-2 receptor, cause canine and human X-linked SCID. This approach is an efficient method for comparative gene mapping and disease identification. 35 refs., 4 figs., 1 tab.

  4. Nonrandom X chromosome inactivation in natural killer cells from obligate carriers of X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Wengler, G.S.; Parolini, O.; Conley, M.E. (Univ. of Tennessee, Memphis (United States) St. Jude Children' s Research Hospital, Memphis, TN (United States)); Allen, R.C. (Baylor College of Medicine, Houston, TX (United States)); Smith, H. (St. Jude Children' s Research Hospital, Memphis, TN (United States))

    1993-01-15

    X-linked severe combined immunodeficiency (XSCID) is characterized by hypogammaglobulinemia, markedly reduced numbers of T cells, absent mitogen responses, decreased numbers of NK cells, and normal or elevated numbers of B cells. The abnormalities in the NK cell and B cell lineages could be attributed to dependence of these cell lineages on T cells or T cell-derived factors, or to expression of the XSCID gene defect in these cell lineages. In past experiments, the authors have examined X chromosome inactivation patterns in T cells and cultured B cells from female obligate carriers of XSCID and have found that both cell lineages demonstrate nonrandom X chromosome inactivation. This indicates that the gene defect is intrinsic to both of these cell lineages. In the present experiments, a polymerase chain reaction technique was used to evaluate X chromosome inactivation patterns in highly purified populations of freshly isolated NK cells, B cells, CD4[sup +] cells, and CD8[sup +] cells from three obligate carriers of XSCID. All four lymphoid cell populations from these three women exhibited exclusive use of a single X as the active X. In contrast, both X chromosomes were used as the active X in neutrophils and monocytes. These findings indicate that the XSCID gene is expressed in the NK cell lineage as well as in T cells and B cells. This observation makes it highly unlikely that the XSCID gene is involved in Ag receptor gene rearrangements. 21 refs., 4 figs.

  5. First Occurrence of Plasmablastic Lymphoma in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Disease Patient and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Maddalena Migliavacca

    2018-02-01

    Full Text Available Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term. To date, eight cases of lymphomas have been described in ADA-SCID patients. Here we report the first case of plasmablastic lymphoma occurring in a young adult with ADA-SCID on long-term ERT, which turned out to be Epstein–Barr virus associated. The patient previously received infusions of genetically modified T cells. A cumulative analysis of the eight published cases of lymphoma from 1992 to date, and the case here described, reveals a high mortality (89%. The most common form is diffuse large B-cell lymphoma, which predominantly occurs in extra nodal sites. Seven cases occurred in patients on ERT and two after haploidentical HSCT. The significant incidence of immunodeficiency-associated lymphoproliferative disorders and poor survival of patients developing this complication highlight the priority in finding a prompt curative treatment for ADA-SCID.

  6. RNA silencing and HIV: A hypothesis for the etiology of the severe combined immunodeficiency induced by the virus

    Directory of Open Access Journals (Sweden)

    Ludwig Linda B

    2008-09-01

    Full Text Available Abstract A novel intrinsic HIV-1 antisense gene was previously described with RNA initiating from the region of an HIV-1 antisense initiator promoter element (HIVaINR. The antisense RNA is exactly complementary to HIV-1 sense RNA and capable of forming ~400 base-pair (bp duplex RNA in the region of the long terminal repeat (LTR spanning the beginning portion of TAR in the repeat (R region and extending through the U3 region. Duplex or double-stranded RNA of several hundred nucleotides in length is a key initiating element of RNA interference (RNAi in several species. This HIVaINR antisense RNA is also capable of forming multiple stem-loop or hairpin-like secondary structures by M-fold analysis, with at least one that perfectly fits the criteria for a microRNA (miRNA precursor. MicroRNAs (miRNAs interact in a sequence-specific manner with target messenger RNAs (mRNAs to induce either cleavage of the message or impede translation. Human mRNA targets of the predicted HIVaINR antisense RNA (HAA microRNAs include mRNA for the human interleukin-2 receptor gamma chain (IL-2RG, also called the common gamma (γc receptor chain, because it is an integral part of 6 receptors mediating interleukin signalling (IL-2R, IL-4R, IL-7R, IL-9R, IL-15R and IL-21R. Other potential human mRNA targets include interleukin-15 (IL-15 mRNA, the fragile × mental retardation protein (FMRP mRNA, and the IL-1 receptor-associated kinase 1 (IRAK1 mRNA, amongst others. Thus the proposed intrinsic HIVaINR antisense RNA microRNAs (HAAmiRNAs of the human immunodeficiency virus form complementary targets with mRNAs of a key human gene in adaptive immunity, the IL-2Rγc, in which genetic defects are known to cause an X-linked severe combined immunodeficiency syndrome (X-SCID, as well as mRNAs of genes important in innate immunity. A new model of intrinsic RNA silencing induced by the HIVaINR antisense RNA in the absence of Tat is proposed, with elements suggestive of both small

  7. A reversal of the shift towards earlier spring phenology in several Mediterranean reptiles and amphibians during the 1998-2013 warming slowdown.

    Science.gov (United States)

    Prodon, Roger; Geniez, Philippe; Cheylan, Marc; Devers, Florence; Chuine, Isabelle; Besnard, Aurelien

    2017-12-01

    Herps, especially amphibians, are particularly susceptible to climate change, as temperature tightly controls many parameters of their biological cycle-above all, their phenology. The timing of herps' activity or migration period-in particular the dates of their first appearance in spring and first breeding-and the shift to earlier dates in response to warming since the last quarter of the 20(th) century has often been described up to now as a nearly monotonic trend towards earlier phenological events. In this study, we used citizen science data opportunistically collected on reptiles and amphibians in the northern Mediterranean basin over a period of 32 years to explore temporal variations in herp phenology. For 17 common species, we measured shifts in the date of the species' first spring appearance-which may be the result of current changes in climate-and regressed the first appearance date against temperatures and precipitations. Our results confirmed the expected overall trend towards earlier first spring appearances from 1983 to 1997, and show that the first appearance date of both reptiles and amphibians fits well with the temperature in late winter. However, the trend towards earlier dates was stopped or even reversed in most species between 1998 and 2013. We interpret this reversal as a response to cooling related to the North Atlantic Oscillation (NAO) in the late winter and early spring. During the positive NAO episodes, for certain species only (mainly amphibians), the effect of a warm weather, which tends to advance the phenology, seems to be counterbalanced by the adverse effects of the relative dryness. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  8. Artemisia vulgaris L. ethanolic leaf extract reverses thrombocytopenia/thrombocytosis and averts end-stage disease of experimental severe Plasmodium berghei murine malaria.

    Science.gov (United States)

    Bamunuarachchi, Gayan S; Ratnasooriya, Wanigasekara D; Premakumara, Sirimal; Udagama, Preethi V

    2014-12-01

    Artemisinin isolated from Artemisia annua is the most potent antimalarial against chloroquine resistant Plasmodium falciparum malaria. We previously reported that the ethanolic leaf extract of Artemisia vulgaris, an invasive weed and the only Artemisia species in Sri Lanka, possess both potent and safe antimalarial activity (in terms of antiparasitic properties) in a P. berghei murine malaria model. We report here a prototype study that investigated antidisease activities of A. vulgaris ethanolic leaf extract (AVELE) in a P. berghei ANKA murine malaria model that elicit pathogenesis similar to falciparum malaria. Profound thrombocytosis and thrombocytopenia in mice were detected in early-stage (Day 3), and at a later stage of infection (Day 6), respectively. Plasmodium berghei infected mice, 7 or 8 days post-infection reached end-stage disease with rapid drop in body temperature and usually die within 24 h, as a consequence of cerebral malaria. Three doses of the AVELE (500, 750 and 1000 mg/kg) were used to assess antidisease activity of A. vulgaris in terms of survival, effects on thrombocyte related pathology and end-stage disease, antipyretic activity, and antinociception, using standard methodology. The 1000 mg/kg dose of AVELE significantly increased survival, reversed the profound thrombocytopenia/ thrombocytosis (p ≤0.01), altered the end-stage disease (p ≤0.05), and manifested significant antipyretic and antinociceptive (p ≤0.05) activities. We conclude that a crude ethanolic leaf extract of A. vulgaris, showed potent antimalarial properties, in terms of antidisease activities; antipyretic activity, peripheral and central antinociception, increased survival, averted end-stage disease and reversed thrombocytopenia/thrombocytosis.

  9. Myocardial reverse remodeling.

    Science.gov (United States)

    Hellawell, Jennifer L; Margulies, Kenneth B

    2012-06-01

    Despite an extensive literature defining the mechanisms and significance of pathological myocardial remodeling, there has been no comprehensive review of the inverse process, often labeled reverse remodeling. Accordingly, the goal of this review is to overview the varied settings in which clinically significant reverse remodeling has been well documented. When available, we reviewed relevant randomized, controlled clinical trials, and meta-analyses with sufficient cardiac imaging data to permit conclusions about reverse remodeling. When these types of studies were not available, relevant case-control studies and case series that employed appropriate methodology were reviewed. Regression of pathological myocardial hypertrophy, chamber shape distortions, and dysfunction occurs in a wide variety of settings. Although reverse remodeling occurs spontaneously in some etiologies of myocardial dysfunction and failure, remodeling is more commonly observed in response to medical, device-based, or surgical therapies, including β-blockers, revascularization, cardiac resynchronization therapy, and valve surgery. Indeed, reverse remodeling following pathophysiologically targeted interventions helps validate that the targeted mechanisms are propelling and/or sustaining pathological remodeling. The diverse clinical settings in which reverse remodeling has been observed demonstrates that myocardial remodeling is bidirectional and occurs across the full spectrum of myocardial disease severity, duration, and etiology. Observations in several settings suggest that recovered hearts are not truly normal despite parallel improvements at organ, tissue, and cellular level. Nevertheless, the link between reverse remodeling and improved outcomes should inspire further research to better understand the mechanisms responsible for both reverse remodeling and persistent deviations from normalcy. © 2010 Blackwell Publishing Ltd.

  10. Nonrandon X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Conley, M.E.; Lavoie, A.; Briggs, C.; Brown, P.; Guerra, C.; Puck, J.M.

    1988-05-01

    X chromosome-linked sever combined immunodeficiency (XSCID) is characterized by markedly reduced numbers of T cells, the absence of proliferative responses to mitogens, and hypogammaglobulinemia but normal or elevated number of B cells. To determine if the failure of the B cells to produce immunoglobulin might be due to expression of the XSCID gene defect in B-lineage cells as well as T cells, the authors analyzed patterns of X chromosome inactivation in B cells from nine obligate carriers of this disorder. A series of somatic cell hybrids that selectively retained the active X chromosome was produced from Epstein-Barr virus-stimulated B cells from each woman. To distinguish between the two X chromosome, the hybrids from each woman were analyzed using an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. In all obligate carriers of XSCID, the B-cell hybrids demonstrated preferential use of a single X chromosome, the nonmutant X, as the active X. To determine if the small number of B-cell hybrids that contained the mutant X were derived from an immature subset of B cells, lymphocytes from three carriers were separated into surface IgM positive and surface IgM negative B cells prior to exposure to Epstein-Barr virus and production of B-cell hybrids. The results demonstrated normal random X chromosome inactivation in B-cell hybrids derived from the less mature surface IgM positive B cells. These results suggest that the XSCID gene product has a direct effect on B cells as well as T cells and is required during B-cell maturation.

  11. Arrested rearrangement of TCR V[beta] genes in thymocytes from children with x-linked severe combined immunodeficiency disease

    Energy Technology Data Exchange (ETDEWEB)

    Sleasman, J.W.; Harville, T.O.; White, G.B.; Barrett, D.J. (Univ. of Florida College of Medicine, Gainsville, FL (United States)); George, J.F. (Univ. of Alabama, Birmingham, AL (United States)); Goodenow, M.M. (Univ. of Florida College of Medicine, Gainsville, FL (United States) Univ. of Alabama, Birmingham, AL (United States))

    1994-07-01

    Human X-linked severe combined immunodeficiency disease (SCID) is an immunodeficiency disorder in which T cell development is arrested in the thymic cortex. B lymphocytes in children with X-linked SCID seem to differentiate normally. X-linked SCID is associated with a mutation in the gene that encodes the IL-2R [gamma]-chain. Because TCR-[beta] gene recombination is a pivotal initial event in T lymphocyte onteogeny within the thymus, the authors hypothesized that a failure to express normal IL-2R[gamma] could lead to impaired TCR-[beta] gene recombination in early thymic development. PCR was used to determine the status of TCR-[beta] gene-segment rearrangements in thymic DNA that had been obtained from children with X-linked SCID. The initial step in TCR-[beta] gene rearrangement, that of D[beta] to J[beta] recombination, was readily detected in all thymus samples from children with X-linked SCID; in contrast, V[beta] to DJ[beta] gene rearrangements were undetectable in the same samples. Both D[beta] to J[beta] and V[beta] to DJ[beta] TCR genes were rearranged in the thymic tissues obtained from immunologically normal children. The authors conclude that TCR[beta]-chain gene rearrangement is arrested in children with X-linked SCID. The results suggest a causative relationship between the failure of TCR [beta]-chain gene arrangements to proceed beyond DJ[beta] rearrangements and the production of a nonfunctional IL-2R [gamma]-chain. 45 refs., 3 figs.

  12. Effectiveness of allogeneic CD3AK cells on transplanted human renal cell cancer in mice with severe combined immune deficiency.

    Science.gov (United States)

    Ge, Lei; Shan, Zhongjie; Han, Qianhe; Zhang, Nan; Zhao, Yang

    2016-01-01

    To assess the activity of allogeneic anti-CD3 antibody induced activated killer (CD3AK) cells on transplanted human renal cell cancer (RCC) in mice with severe combined immune deficiency (SCID), thus to provide theoretical and experimental support for clinical application of allogeneic CD3AK cells in the treatment of RCC. A culture system which can massively increase allogeneic CD3AK cells was constructed. CCK-8 method was used to detect lethal effect of allogeneic CD3AK cells on human OS-RC-2 renal cancer cell line. Then, tumor-bearing mice models were constructed. SCID mice were randomly divided into four groups: group A (caudal vein was injected with allogeneic CD3AK cells before tumor bearing), group B (the control group of group A: caudal vein was injected with PBS before tumor bearing), group C (caudal vein was injected with allogeneic CD3AK cells after tumor bearing) and group D (the control group of group C: caudal vein was injected with PBS after tumor bearing), and spleen parameters were calculated to observe any inhibitory effect of allogeneic CD3AK cells on the growth of renal cancer cells, as well as their effect on the immune system of mice. Compared with the control groups B and D, spleen parameters of groups A and C increased significantly (p0.05); compared with the control groups B and D, tumor weight of groups A and C decreased significantly and tumors grew slowly (pcancer in mice with SCID. Also CD3AK cells expressed certain preventive effect on the development of implanted cancer in SCID mice; allogeneic CD3AK cells possessed antitumor activity and could enhance the immunologic functions of SCID mice with human renal cell-bearing cancer.

  13. The carrier prevalence of severe combined immunodeficiency, lavender foal syndrome and cerebellar abiotrophy in Arabian horses in South Africa.

    Science.gov (United States)

    Tarr, C J; Thompson, P N; Guthrie, A J; Harper, C K

    2014-07-01

    The carrier prevalence of severe combined immunodeficiency (SCID), lavender foal syndrome (LFS) and cerebellar abiotrophy (CA) in Arabian foals in South Africa was determined in order to quantify the potential impact of these conditions locally. Furthermore, the carrier prevalence of SCID prior to and following the introduction of a genetic test was compared to evaluate the effect of testing in the population. To estimate the carrier prevalence of SCID, LFS and CA in registered purebred Arabians born in South Africa in the 2004/5 and 2009/10 foaling seasons and compare the changes in prevalence in these disorders between the 2 groups of foals. Cross-sectional survey. Samples were collected from individuals randomly selected from 2 populations of purebred Arabian foals born during the 2004/5 and 2009/10 foaling seasons. Genetic testing for SCID, LFS and CA was performed on DNA extracts using specific polymerase chain reactions, with the products being analysed using fragment analysis on a genetic analyser. The carrier prevalence of LFS and CA for the 2009/10 season was 11.7% (95% confidence interval [CI] 7.6-17.0%) and 5.1% (95% CI 2.5-9.1%), respectively, with no statistically significant change in prevalence between the 2004/5 and 2009/10 foaling seasons. However, the carrier prevalence of SCID was found to have decreased significantly from 6.4% (95% CI 4.8-8.3%) in the 2004/5 foals to 3.4% (95% CI 2.2-5.1%) in the 2009/10 foals (P = 0.009). The results of this study indicate that genetic screening of Arabian horses for SCID may have played a role in significantly reducing the carrier prevalence within the breeding population and thereby reducing the birth of clinically affected individuals. This study provides an indication of the positive effect of genetic screening for specific conditions in horses. © 2013 EVJ Ltd.

  14. Combined intracavernous vasoactive drugs and sildenafil citrate in treatment of severe erectile dysfunction not responding to on-demand monotherapy.

    Science.gov (United States)

    Al-Adl, Ahmed M; Abdel-Wahab, Osama; El-Karamany, Tarek; Aal, Ashraf A

    2011-06-01

    To investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1). The study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, penile colour Doppler ultrasonography (CDUS) for peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) with an ICI test using 0.25 mL of trimix of papaverine, PGE1 and phentolamine. Testosterone, prolactin and cholesterol levels were assessed. Patients received 25 mg sildenafil daily for 8 weeks, combined with twice weekly ICI with 0.25 mL of trimix. After treatment, the Erection Hardness Score (EHS), penile CDUS with ICI and ED Inventory of Treatment Satisfaction were assessed. The mean (SD) SHIM-5 score before treatment was 8.3 (0.5) in 15 of the 40 men and 6.3 (0.4) in 25. Penile haemodynamics were normal in five (13%), showed arterial insufficiency in five (13%), venous occlusive disease in 26 (65%) and mixed vascular in four (10%). There was an improved SHIM-5 score in 28 (70%) patients, as shown by their haemodynamic values, duration of erection and EHS with therapy, and 66% satisfaction with treatment. Adverse effects (penile pain, headache, facial flushing, dyspepsia, nasal congestion, dizziness) were reported in 17 patients (43%). Chronic use of trimix plus daily low-dose sildenafil improved penile haemodynamics in these patients with ED not responding to on-demand phosphodiesterase-5 inhibitors or ICI with PGE1 monotherapy.

  15. Independent and combined association of overall physical fitness and subjective well-being with fibromyalgia severity : the al-Ándalus project

    NARCIS (Netherlands)

    Estévez-López, Fernando; Gray, Cindy M; Segura-Jiménez, Víctor; Soriano-Maldonado, Alberto; Álvarez-Gallardo, Inmaculada C; Arrayás-Grajera, Manuel J; Carbonell-Baeza, Ana; Aparicio, Virginia A; Delgado-Fernández, Manuel; Pulido-Martos, Manuel

    PURPOSE: The present study aimed: (1) to test the associations of overall physical fitness and subjective well-being with fibromyalgia severity and (2) to determine whether the combination of overall physical fitness and subjective well-being is associated with fibromyalgia severity among adult

  16. Reverse logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); S.D.P. Flapper; R. Dekker (Rommert)

    2002-01-01

    textabstractThis paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In

  17. Rapid and sensitive detection of novel avian-origin influenza A (H7N9 virus by reverse transcription loop-mediated isothermal amplification combined with a lateral-flow device.

    Directory of Open Access Journals (Sweden)

    Yiyue Ge

    Full Text Available A severe disease in humans caused by a novel avian-origin influenza A (H7N9 virus emerged in China recently, which has caused at least 128 cases and 26 deaths. Rapid detection of the novel H7N9 virus is urgently needed to differentiate the disease from other infections, and to facilitate infection control as well as epidemiologic investigations. In this study, a reverse transcription loop-mediated isothermal amplification combined with a lateral flow device (RT-LAMP-LFD assay to rapidly detect H7N9 virus was developed and evaluated. The RT-LAMP primers were designed to target the haemagglutinin (HA and neuraminidase (NA genes of H7N9 virus. Results of 10-fold dilution series assays showed that analysis of RT-LAMP products by the LFD method was as sensitive as real-time turbidity detection, and that the analytic sensitivities of the HA and NA RT-LAMP assays were both 10 copies of synthetic RNA. Furthermore, both the assays showed 100% clinical specificity for identification of H7N9 virus. The performance characteristics of the RT-LAMP-LFD assay were evaluated with 80 clinical specimens collected from suspected H7N9 patients. The NA RT-LAMP-LFD assay was more sensitive than real time RT-PCR assay. Compared with a combination of virus culture and real-time RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value of the RT-LAMP-LFD assay were all 100%. Overall, The RT-LAMP-LFD assay established in this study can be used as a reliable method for early diagnosis of the avian-origin influenza A (H7N9 virus infection.

  18. Detection of tumor cell-specific mRNA in the peripheral blood of patients with breast cancer—evaluation of several markers with real-time reverse transcription-PCR.

    Science.gov (United States)

    Andergassen, Ulrich; Hofmann, Simone; Kölbl, Alexandra C; Schindlbeck, Christian; Neugebauer, Julia; Hutter, Stefan; Engelstädter, Verena; Ilmer, Matthias; Friese, Klaus; Jeschke, Udo

    2013-01-08

    It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19). B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy.

  19. Detection of Tumor Cell-Specific mRNA in the Peripheral Blood of Patients with Breast Cancer — Evaluation of Several Markers with Real-Time Reverse Transcription-PCR

    Directory of Open Access Journals (Sweden)

    Ulrich Andergassen

    2013-01-01

    Full Text Available It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19. B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy.

  20. A confirmatory study of the Combined Index of Severity of Fibromyalgia (ICAF*): factorial structure, reliability and sensitivity to change

    Science.gov (United States)

    2011-01-01

    Background Fibromyalgia (FM) is a complex syndrome that affects many aspects of the patients life and it is very difficult to evaluate in clinical practice. A recent study has developed the Combined Index of Severity of Fibromyalgia (ICAF), an instrument that evaluates diverse aspects of FM and offers five indices: emotional, physical, active coping, passive coping and total. The objective of this study is to confirm the structure of the ICAF, check its test-retest reliability, assess its sensitivity to change, and compare the results obtained in a sample of patients with fibromyalgia with another sample of healthy controls. Methods A total of 232 patients took part in the study, 228 women and 4 men, with a mean age of 47.73 years of age (SD = 8.61) and a time of disease evolution since diagnosis of 4.28 years (SD = 4.03). The patients from the FM group completed the ICAF. Between one and two weeks later, they again attended the clinic and complete the 59 items on the ICAF (retest) and immediately afterwards they began treatment (according to daily clinical practice criteria). A sample of healthy subjects was also studied as a control group: 110 people were included (106 women and 4 men) with a mean age of 46.01 years of age (SD = 9.35). The study was conducted in Spain. Results The results obtained suggest that the four-factor model obtained in the previous study adequately fits the data obtained in this study. The test-retest reliability and internal consistency were all significant and show a high degree of correlation for all the factors as well as in overall score. With the exception of the passive coping factor, all the other scores, including the overall score, were sensitive to change after the therapeutic intervention. The ICAF scores of the patients with fibromyalgia compared with those of the control group were markedly different. Conclusions The findings suggest that the ICAF is a valid, reliable, sensitive to change instrument with the added advantage

  1. A confirmatory study of the Combined Index of Severity of Fibromyalgia (ICAF*: factorial structure, reliability and sensitivity to change

    Directory of Open Access Journals (Sweden)

    Rejas Javier

    2011-06-01

    Full Text Available Abstract Background Fibromyalgia (FM is a complex syndrome that affects many aspects of the patients life and it is very difficult to evaluate in clinical practice. A recent study has developed the Combined Index of Severity of Fibromyalgia (ICAF, an instrument that evaluates diverse aspects of FM and offers five indices: emotional, physical, active coping, passive coping and total. The objective of this study is to confirm the structure of the ICAF, check its test-retest reliability, assess its sensitivity to change, and compare the results obtained in a sample of patients with fibromyalgia with another sample of healthy controls. Methods A total of 232 patients took part in the study, 228 women and 4 men, with a mean age of 47.73 years of age (SD = 8.61 and a time of disease evolution since diagnosis of 4.28 years (SD = 4.03. The patients from the FM group completed the ICAF. Between one and two weeks later, they again attended the clinic and complete the 59 items on the ICAF (retest and immediately afterwards they began treatment (according to daily clinical practice criteria. A sample of healthy subjects was also studied as a control group: 110 people were included (106 women and 4 men with a mean age of 46.01 years of age (SD = 9.35. The study was conducted in Spain. Results The results obtained suggest that the four-factor model obtained in the previous study adequately fits the data obtained in this study. The test-retest reliability and internal consistency were all significant and show a high degree of correlation for all the factors as well as in overall score. With the exception of the passive coping factor, all the other scores, including the overall score, were sensitive to change after the therapeutic intervention. The ICAF scores of the patients with fibromyalgia compared with those of the control group were markedly different. Conclusions The findings suggest that the ICAF is a valid, reliable, sensitive to change instrument with

  2. Direct oral anticoagulant reversal

    DEFF Research Database (Denmark)

    Dzeshka, Mikhail S; Pastori, Daniele; Lip, Gregory Y H

    2017-01-01

    to manage bleeding depending on severity, with a particular focus on specific reversal agents, are discussed. Expert commentary: Due to short half-life of NOACs compared to warfarin, discontinuation of drug, mechanical compression, and volume substitution are considered to be sufficient measures in most...... of bleeding cases. In case of life-threatening bleeding or urgent surgery, hemostasis can be achieved with non-specific reversal agents (prothrombin complex concentrates) in patients treated with factor Xa inhibitor until specific antidotes (andexanet α and ciraparantag) will receive approval. Thus far......, idarucizumab has been the only reversal agent approved for dabigatran....

  3. Two-step ion-exchange chromatographic purification combined with reversed-phase chromatography to isolate C-peptide for mass spectrometric analysis.

    Science.gov (United States)

    Kabytaev, Kuanysh; Durairaj, Anita; Shin, Dmitriy; Rohlfing, Curt L; Connolly, Shawn; Little, Randie R; Stoyanov, Alexander V

    2016-02-01

    A liquid chromatography with mass spectrometry on-line platform that includes the orthogonal techniques of ion exchange and reversed phase chromatography is applied for C-peptide analysis. Additional improvement is achieved by the subsequent application of cation- and anion-exchange purification steps that allow for isolating components that have their isoelectric points in a narrow pH range before final reversed-phase mass spectrometry analysis. The utility of this approach for isolating fractions in the desired "pI window" for profiling complex mixtures is discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Reversible simulations of elastic collisions

    Energy Technology Data Exchange (ETDEWEB)

    Perumalla, Kalyan S.; Protopopescu, Vladimir A.

    2013-05-01

    Consider a system of N identical hard spherical particles moving in a d-dimensional box and undergoing elastic, possibly multi-particle, collisions. We develop a new algorithm that recovers the pre-collision state from the post-collision state of the system, across a series of consecutive collisions, \\textit{with essentially no memory overhead}. The challenge in achieving reversibility for an n-particle collision (where, in general, n<< N) arises from the presence of nd-d-1 degrees of freedom (arbitrary angles) during each collision, as well as from the complex geometrical constraints placed on the colliding particles. To reverse the collisions in a traditional simulation setting, all of the particular realizations of these degrees of freedom (angles) during the forward simulation must be tracked. This requires memory proportional to the number of collisions, which grows very fast with N and d, thereby severely limiting the \\textit{de facto} applicability of the scheme. This limitation is addressed here by first performing a pseudo-randomization of angles, which ensures determinism in the reverse path for any values of n and d. To address the more difficult problem of geometrical and dynamic constraints, a new approach is developed which correctly samples the constrained phase space. Upon combining the pseudo-randomization with correct phase space sampling, perfect reversibility of collisions is achieved, as illustrated for n<=3, d=2, and n=2, d=3. This result enables, for the first time, reversible simulations of elastic collisions with essentially zero memory accumulation. In principle, the approach presented here could be generalized to larger values of n, which would be of definite interest for molecular dynamics simulations at high densities.

  5. Reverse Osmosis

    Indian Academy of Sciences (India)

    ment of Civil Engineering and is presently the. Chairman of Center for. Sustainable Technologies,. Indian Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis,.

  6. Reverse Osmosis

    Indian Academy of Sciences (India)

    and is an Associate Faculty at Center for Sustainable. Technologies, Indian. Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis, desalinatiion, seawater, water.

  7. Reverse Osmosis

    Indian Academy of Sciences (India)

    /fulltext/reso/012/05/0037-0040. Keywords. Osmosis; reverse osmosis; desalinatiion; seawater; water purification. Author Affiliations. Sudhakar M Rao1. Department of Civil Engineering, Indian Institute of Science, Bangalore 560012, India.

  8. Reversible Sterilization

    Science.gov (United States)

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  9. Laparoscopic Surgical Treatment of Severe Obesity Combined with Gastroesophageal Reflux Disease: A Pilot Randomized Two-Arm Controlled Clinical Study

    Science.gov (United States)

    Ospanov, Oral B.; Orekeshova, Akzhunis M.; Fursov, Roman A.; Yelemesov, Aset A.

    2016-01-01

    Obesity and gastroesophageal reflux disease (GERD) are serious medical, social, and economic problems of modern society. A pilot randomized two-arm controlled clinical study was conducted to compare laparoscopic plication of the greater gastric curvature combined with Nissen fundoplication (LFN+LGP) versus only Nissen fundoplication (LFN). The…

  10. Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST).

    Science.gov (United States)

    Weisenseel, Peter; Reich, Kristian; Griemberg, Wiebke; Merten, Katharina; Gröschel, Christine; Gomez, Natalie Nunez; Taipale, Kirsi; Bräu, Beate; Zschocke, Ina

    2017-02-01

    While treatment of patients with moderate-to-severe psoriasis using a combination of fumaric acid esters (FAE, Fumaderm® ) and phototherapy (UV) is common practice, there have been hardly any studies investigating this regimen. Available information is limited to data from a small pilot study. The objective of the present study was to evaluate FAE/UV combination therapy in a larger patient cohort with moderate-to-severe psoriasis. In this prospective noninterventional multicenter study, data from patients treated with FAE/UV combination therapy was assessed with regard to efficacy (PGA' PASI, DLQI, EQ-5D), safety, and dosage over a twelve-month period. The findings were subsequently compared to data from a previous retrospective study on FAE monotherapy. Data from 363 patients was included in the analysis. Efficacy measures improved substantially on combination therapy. Compared to FAE monotherapy, FAE/UV therapy led to a faster clinical response, however, there was no difference in efficacy after 12 months. Neither the duration nor the type of phototherapy had an impact on efficacy. In general, combination therapy was well tolerated. Seven percent of patients experienced adverse events. FAE/UV combination therapy is effective and well tolerated in patients with moderate-to-severe psoriasis. Such treatment may induce a faster therapeutic response, and appears to be useful, particularly in the first three months of FAE therapy. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  11. A combination of Latarjet and Remplissage for treatment of severe glenohumeral instability and bone loss. A case report

    Science.gov (United States)

    Ranne, Juha O.; Sarimo, Janne J.; Heinonen, Olli J.; Orava, Sakari Y.

    2013-01-01

    Recurrent glenohumeral instability is challenging to treat when large bony defects are present in the anterior glenoid and there is a large Hill–Sachs lesion. We present a case with extensive glenoid and humeral bone loss treated with open Latarjet procedure combined with posterior arthroscopic Remplissage. 3.5 years after surgery, there have been no dislocations or any subjective signs of instability. After half a year, the patient was able to return to work as an airline pilot. Constant score has improved from 33 to 74 and the Oxford instability score from 8 to 46. We find that in young patients with difficult instability combining the Latarjet and Remplissage is a good and replicable method. PMID:24403748

  12. Optimal duration of combined psychotherapy and pharmacotherapy for patients with moderate and severe depression: A meta-analysis

    DEFF Research Database (Denmark)

    Møldrup, Claus; Østergaard, Svetlana

    2011-01-01

    Background: To investigate the most effective duration of combined psychotherapy and pharmacotherapy for achieving remission and preventing relapse in depressive patients compared to pharmacotherapy alone. Methods: A systematic review of English articles using PubMed, EMBASE, Web of Science......, the Cochrane Library, and PsychINFO was performed in September 2009. Clinical studies comparing pharmacotherapy alone with pharmacotherapy in combination with a psychological intervention for depression treatment that reported response, remission or relapse as outcomes were included in the analysis. For each...... of the studies, clinical binary outcomes such as response, remission or relapse were extracted. Result: All pooled analyses were based on random-effects models. Twenty-one articles describing the influence of additional psychotherapy on remission and 15 articles reporting the influence on relapse in depression...

  13. Evaluation of several electrolyte mixture-cathode material combinations in electrodeposition of americium radioisotopes for alpha-spectrometric measurements.

    Science.gov (United States)

    Krmpotić, Matea; Rožmarić, Martina; Benedik, Ljudmila

    2017-10-01

    Three different types of electrolytes, subsequently modified and adjusted, in combination with three cathode materials used as source backings were analysed for electrodeposition of americium isotopes for alpha-spectrometric measurements. The obtained results are discussed in terms of electrodeposition yield and source quality (source homogeneity and spectral resolution, FWHM). The optimal conditions for source preparation are provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report

    Directory of Open Access Journals (Sweden)

    Podda Mauro

    2010-05-01

    Full Text Available Abstract Introduction A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension. Case presentation We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy. Conclusion We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.

  15. Severe morbidity according to sex in the era of combined antiretroviral therapy: the ANRS CO3 Aquitaine Cohort.

    Science.gov (United States)

    Hessamfar, Mojgan; Colin, Céline; Bruyand, Mathias; Decoin, Madeleine; Bonnet, Fabrice; Mercié, Patrick; Neau, Didier; Cazanave, Charles; Pellegrin, Jean-Luc; Dabis, François; Morlat, Philippe; Chêne, Geneviève

    2014-01-01

    To describe trends and determinants of severe morbidity in HIV-infected women and men. A French prospective cohort of HIV-infected patients of both sexes and all transmission categories. We used hospital admission data from January 2000 to December 2008. A severe morbid event (SME) was defined as a clinical event requiring hospitalization for ≥48 h, several events could be reported during hospitalization. Yearly incidence rates of SME were estimated and compared using Generalized Estimating Equations. Among 4,987 patients (27% women), followed for a median of 8.7 years, 1,473 (30%) were hospitalized (3,049 hospitalizations for 5,963 SME). The yearly incidence rate of hospitalization decreased in men, from 155 in 2000 to 80/1,000 person-years (PY) in 2008 and in women, from 125 to 71/1,000 PY, (p50 years, HIV RNA >10,000 copies, CD4 <500/mm3, AIDS stage, hepatitis C co-infection and cardiovascular risk factors (diabetes, high blood pressure, and tobacco use) were associated with SME. HIV-infected individuals in care in France require less and less frequently hospitalization. Women are now presenting with severe hepatic and cardio-vascular events. Disparities in SME between men and women are primarily explained by different exposure patterns to risk factors. Women should be targeted to benefit cardiovascular prevention policies as well as men.

  16. Severe morbidity according to sex in the era of combined antiretroviral therapy: the ANRS CO3 Aquitaine Cohort.

    Directory of Open Access Journals (Sweden)

    Mojgan Hessamfar

    Full Text Available To describe trends and determinants of severe morbidity in HIV-infected women and men.A French prospective cohort of HIV-infected patients of both sexes and all transmission categories.We used hospital admission data from January 2000 to December 2008. A severe morbid event (SME was defined as a clinical event requiring hospitalization for ≥48 h, several events could be reported during hospitalization. Yearly incidence rates of SME were estimated and compared using Generalized Estimating Equations.Among 4,987 patients (27% women, followed for a median of 8.7 years, 1,473 (30% were hospitalized (3,049 hospitalizations for 5,963 SME. The yearly incidence rate of hospitalization decreased in men, from 155 in 2000 to 80/1,000 person-years (PY in 2008 and in women, from 125 to 71/1,000 PY, (p50 years, HIV RNA >10,000 copies, CD4 <500/mm3, AIDS stage, hepatitis C co-infection and cardiovascular risk factors (diabetes, high blood pressure, and tobacco use were associated with SME.HIV-infected individuals in care in France require less and less frequently hospitalization. Women are now presenting with severe hepatic and cardio-vascular events. Disparities in SME between men and women are primarily explained by different exposure patterns to risk factors. Women should be targeted to benefit cardiovascular prevention policies as well as men.

  17. Rabbit alveolar macrophages contain a Ca2+-sensitive, 41,000-dalton protein which reversibly blocks the "barbed" ends of actin filaments but does not sever them.

    Science.gov (United States)

    Southwick, F S; DiNubile, M J

    1986-10-25

    A 41,000-dalton Ca2+-sensitive actin-modulating protein has been purified from rabbit alveolar macrophages using ion exchange and gel filtration chromatography. On sodium dodecyl-polyacrylamide gel electrophoresis, this macrophage protein migrates more rapidly than actin and fails to cross-react with polyclonal anti-actin antibody. It has a Stokes radius of 3.0 nm and an isoelectric point of 6.6. In the presence of micromolar Ca2+ this 41,000-Da protein: reduces the viscosity of polymerized actin, nucleates actin filament assembly, causes a nearly instantaneous increase in fluorescence intensity of subcritical concentrations of pyrenyl-actin (estimated KD of the pyrene actin-macrophage protein complex, 5 X 10(-8) M), increases the critical concentration of actin by 0.65 microM (molar ratios of protein/actin, 1/100-1/10), blocks actin monomer depolymerization from the "barbed" filament ends, and does not sever preformed actin filaments. The ability of this protein to block filament ends is rapidly and completely inhibited by lowering free calcium ion concentration below the micromolar range.

  18. Effect of ropivacaine combined with pancuronium on neuromuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study

    Directory of Open Access Journals (Sweden)

    Angélica de Fátima Braga

    2015-04-01

    Full Text Available BACKGROUND AND OBJECTIVES: The local anesthetic effects on neuromuscular junction and its influence on blockade produced by nondepolarizing neuromuscular blockers are still under-investigated; however, this interaction has been described in experimental studies and in humans. The aim of this study was to evaluate in vitro the interaction between ropivacaine and pancuronium, the influence on transmission and neuromuscular blockade, and the effectiveness of neostigmine and 4-aminopyridine to reverse the blockade. METHODS: Rats were divided into groups (n = 5 according to the study drug: ropivacaine (5 µg mL-1; pancuronium (2 µg mL-1; ropivacaine + pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2 µg mL-1 and 20 µg mL-1, respectively. The effects of ropivacaine on membrane potential and miniature endplate potential, the amplitude of diaphragm responses before and 60 min after the addition of ropivacaine (degree of neuromuscular blockade with pancuronium and with the association of pancuronium-ropivacaine, and the effectiveness of neostigmine and 4-aminopyridine on neuromuscular block reversal were evaluated. RESULTS: Ropivacaine did not alter the amplitude of muscle response (the membrane potential, but decreased the frequency and amplitude of the miniature endplate potential. Pancuronium blockade was potentiated by ropivacaine, and partially and fully reversed by neostigmine and 4-aminopyridine, respectively. CONCLUSIONS: Ropivacaine increased the neuromuscular block produced by pancuronium. The complete antagonism with 4-aminopyridine suggests presynaptic action of ropivacaine.

  19. Correction of murine rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene

    NARCIS (Netherlands)

    N.P. van Til (Niek); H. de Boer (Helen); N. Mashamba (Nomusa); A. Wabik (Agnieszka); M.W. Huston (Marshall W.); T.P. Visser (Trudi); R.J. Fontana (Robert); P.L. Poliani (Pietro); B. Cassani (Barbara); F. Zhang (Fang); A.J. Thrasher (Adrian); A. Anna (Villa); G. Wagemaker (Gerard)

    2012-01-01

    textabstractRecombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We

  20. The association of eating styles with weight change after an intensive combined lifestyle intervention for children and adolescents with severe obesity

    NARCIS (Netherlands)

    Halberstadt, J.; Strien, T. van; Vet, E. de; Eekhout, I.; Braet, C.; Seidell, J.C.

    2016-01-01

    The main purpose of this prospective intervention study was to determine whether eating styles after an intensive, partly inpatient, one year combined lifestyle intervention are associated with weight change in the following year in severely obese children and adolescents. A total of 120

  1. The association of eating styles with weight change after an intensive combined lifestyle intervention for children and adolescents with severe obesity.

    NARCIS (Netherlands)

    Halberstadt, J.; van Strien, T.; de Vet, E.W.M.L.; Eekhout, I.; Braet, C.; Seidell, J.C.

    2016-01-01

    The main purpose of this prospective intervention study was to determine whether eating styles after an intensive, partly inpatient, one year combined lifestyle intervention are associated with weight change in the following year in severely obese children and adolescents.A total of 120 participants

  2. Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis – A systematic review with meta-analysis and trial sequential analysis

    DEFF Research Database (Denmark)

    Sjövall, Karl Fredrik Lennart; Perner, Anders; Hylander Møller, Morten

    2017-01-01

    Objectives To assess benefits and harms of empirical mono- vs. combination antibiotic therapy in adult patients with severe sepsis in the intensive care unit (ICU). Methods We performed a systematic review according to the Cochrane Collaboration methodology, including meta-analysis, risk of bias ...

  3. Seeding efficiency of primitive human hematopoietic cells in nonobese diabetic/severe combined immune deficiency mice: implications for stem cell frequency assessment

    NARCIS (Netherlands)

    P.B. van Hennik; A.E. de Koning (Alexandra); R.E. Ploemacher (Robert)

    1999-01-01

    textabstractNonobese diabetic/severe combined immune deficiency (NOD/SCID) mouse repopulating cells (SRC) have been proposed to represent a more primitive human stem cell subset than the cobblestone area-forming cell (CAFC) week (wk) 6 or the long-term

  4. Combining Ketamine and Virtual Reality Pain Control During Severe Burn Wound Care: One Military and One Civilian Patient

    Science.gov (United States)

    2011-01-01

    cleanings. Key Words. Analgesia ; Burn Pain ; Wound Care; Distraction; Virtual Reality Introduction Opioids are the cornerstone analgesics for patients with...severe burn. Ketamine is used to potentiate opioid analgesia and to allow better pain control without exces- sive opioid side effects [10,11]. In...signals transmitted from the pain receptors to the brain, thereby decreasing pain . In contrast to the pharmacologic mechanism for ketamine analgesia

  5. Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity.

    Science.gov (United States)

    Taha, Dhiaa A; Zgair, Atheer; Lee, Jong Bong; de Moor, Cornelia H; Barrett, David A; Bruce, Kimberley D; Sungelo, Mitchell; Eckel, Robert H; Gershkovich, Pavel

    2017-03-30

    The association of lipophilic statins with plasma lipoproteins in the presence of disturbed acid-base balance can modify the pharmacokinetics and tissue distribution of these drugs, resulting in alteration in their efficacy and toxicity profiles. The purpose of this study is to elucidate the role of hyperlipidaemia alone or in combination with acidosis/alkalosis in the development and potentiation of statin-induced myotoxicity. Statins association with plasma lipoproteins was examined under conditions of physiological and altered pH levels. The effect of this association on cellular uptake and myotoxicity of statins was also assessed at different pH levels using C2C12 cells that overexpress lipoprotein lipase. Lipophilic simvastatin displayed considerable association with the non-polar lipoprotein fractions (triglyceride-rich lipoproteins and low-density lipoprotein). This association contributed to increased cellular uptake of simvastatin by C2C12 cells through lipoprotein lipase-mediated process, resulting in enhanced muscle toxicity in hyperlipidaemic conditions. Furthermore, a combination of low pH environment (representing acidosis) and hyperlipidaemia increased the association of simvastatin with plasma lipoproteins causing potentiation of cellular uptake and myotoxicity of this drug. Comorbidities such as hyperlipidaemia, especially when coincident with acidosis, can enhance statin-associated muscle toxicity, and therefore require extra caution by prescribing clinicians. Hydrophilic rather than lipophilic statins could be a preferable choice in this patient population. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Psychiatric side effects induced by supraphysiological doses of combinations of anabolic steroids correlate to the severity of abuse.

    Science.gov (United States)

    Pagonis, Thomas A; Angelopoulos, Nikiforos V; Koukoulis, George N; Hadjichristodoulou, Christos S

    2006-12-01

    The objective of our study was to evaluate the psychological consequences of real-world AAS use in athletes abusing such agents, in comparison with a placebo and control group of comparable athletes, while correlating the severity of abuse with the side effects observed. The hypothesis tested by the study was that the use of AAS induces a wide range of psychological side effects whose impact and emergence is dependent upon the severity of the abuse. The study includes a substantial group of AAS abusing athletes and two more groups demographically similar to the first, one composed of athletes not using any substance and a placebo group. All athletes were stratified according to the severity of AAS abuse. Psychometric instruments were applied to all athletes in specific time intervals, dependent to the AAS abusers' regimens, providing us with a final psychological profile that was to be compared to the pre-study profile. All results were comparable (within and between groups) for statistically significant differences and correlated to the severity of the abuse. Homogeneity of all groups was safeguarded by random doping controls, monitoring of drug levels and analysis of all self obtained drugs by method of liquid chromatography/mass spectrometry. All athletes were provided with a common exercise and dietary regime, so common training and nutritional conditions were achieved. We studied a cohort of 320 body-building, amateur and recreational athletes, of whom 160 were active users of AAS (group C), 80 users administering placebo drugs (group B) and 80 not abusing any substance (Group A). Group C athletes were stratified according to AAS abuse parameters, thus providing us with three subgroups of "light, medium and heavy abuse". Athletes of groups A and B were included in a "no abuse" subgroup. The psychometric instruments used were the Symptoms Check List-90 (SCL-90) and the Hostility and Direction of Hostility Questionnaire (HDHQ). The psychometric evaluations took

  7. A combination of early warning score and lactate to predict intensive care unit transfer of inpatients with severe sepsis/septic shock

    Science.gov (United States)

    Yoo, Jung-Wan; Lee, Ju Ry; Jung, Youn Kyung; Choi, Sun Hui; Son, Jeong Suk; Kang, Byung Ju; Park, Tai Sun; Huh, Jin-Won; Lim, Chae-Man; Koh, Younsuck

    2015-01-01

    Background/Aims The modified early warning score (MEWS) is used to predict patient intensive care unit (ICU) admission and mortality. Lactate (LA) in the blood lactate (BLA) is measured to evaluate disease severity and treatment efficacy in patients with severe sepsis/septic shock. The usefulness of a combination of MEWS and BLA to predict ICU transfer in severe sepsis/septic shock patients is unclear. We evaluated whether use of a combination of MEWS and BLA enhances prediction of ICU transfer and mortality in hospitalized patients with severe sepsis/septic shock. Methods Patients with severe sepsis/septic shock who were screened or contacted by a medical emergency team between January 2012 and August 2012 were enrolled at a university-affiliated hospital with ~2,700 beds, including 28 medical ICU beds. Results One hundred patients were enrolled and the rate of ICU admittance was 38%. MEWS (7.37 vs. 4.85) and BLA concentration (5 mmol/L vs. 2.19 mmol/L) were significantly higher in patients transferred to ICU than those in patients treated in general wards. The combination of MEWS and BLA was more accurate than MEWS alone in terms of ICU transfer (C-statistics: 0.898 vs. 0.816, p = 0.019). The 28-day mortality rate was 19%. MEWS was the only factor significantly associated with 28-day mortality rate (odds ratio, 1.462; 95% confidence interval, 1.122 to 1.905; p = 0.005). Conclusions The combination of MEWS and BLA may enhance prediction of ICU transfer in patients with severe sepsis/septic shock. PMID:26161013

  8. Multimodal Therapy for the Treatment of Severe Ischemic Stroke Combining Endovascular Embolectomy and Stenting of Long Intracranial Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Matjaž Bunc

    2010-01-01

    Case Report. We present a case of a 49-year-old female patient who—according to the National Institute of Health Stroke Scale (NIHSS—was rated as 19 due to acute occlusion of the horizontal segment of the left middle cerebral artery (MCA. After failed i.v. thrombolysis, only a part of the clot could be evacuated by the endovascular approach—without restoration of blood flow. Normal patency of the left MCA was re-established after stenting. Within 72 hours, the patient had an NIHSS score of 14, with a small haematoma in the left hemisphere. Conclusion. In our case multimodal therapy combining i.v. thrombolysis, mechanical disruption of thrombus, MCA stenting and platelet function antagonists, resulted in successful recanalization of the acutely occluded left MCA.

  9. Combined intracavernous vasoactive drugs and sildenafil citrate in treatment of severe erectile dysfunction not responding to on-demand monotherapy

    OpenAIRE

    Al-Adl, Ahmed M.; Abdel-Wahab, Osama; El-Karamany, Tarek; Aal, Ashraf A.

    2011-01-01

    Objective To investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1). Patients and methods The study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, pen...

  10. Discrimination between mild and severe Citrus tristeza virus isolates with a rapid and highly specific real-time reverse transcription-polymerase chain reaction method using TaqMan LNA probes.

    Science.gov (United States)

    Ruiz-Ruiz, S; Moreno, P; Guerri, J; Ambrós, S

    2009-03-01

    Severe isolates of Citrus tristeza virus (CTV) inducing seedling yellows (SY) and/or stem pitting (SP) in grapefruit or sweet orange are a major threat for the citrus industry worldwide. Identification of these CTV variants was achieved by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) using a general primer set and three TaqMan locked nucleic acids (LNA) probes targeting sequences characteristic of severe, mild (non-SY, non-SP), and T36-like isolates. Successful amplification was achieved from fresh or silica-desiccated CTV-infected samples and all isolates but one reacted with one or more probes. Standard curves using RNA transcripts homologous to the three probes allowed a reproducible quantitative assay, with a wide dynamic range of detection starting with 10(2) copies. RT-PCR assays with homologous and heterologous transcript RNA mixes demonstrated that each probe reacted only with its cognate sequence which was detected even at ratios below 2.5%. Analysis of 56 pathogenically distinct CTV isolates from 20 countries showed that mild isolates reacted only with the mild probe, whereas severe SP and SY isolates reacted with the severe-SP or the T36-like probes, respectively, and often with a second probe. This procedure can be useful to identify and control potentially dangerous CTV isolates in areas affected only by mild isolates.

  11. Reverse mortgages.

    Science.gov (United States)

    Farnesi, D

    1995-09-01

    Elders and their families are often caught in a financial bind when it comes to paying for much-needed home care services. Reverse mortgages may offer a solution to elderly home care clients who own their homes but have a limited income with which to maintain their independence.

  12. Reversible Computing

    Science.gov (United States)

    1980-02-01

    will have been introduced. 9. Reversible celular autemata We shall assume the reader to have some familiarity with the concept of cel- lular...10003 Mr. Kin B. Thcmpson 1 copy Technical Director Information Systems Divisia.i Naval Research Laboratory (OP-91T) Technical Information Division

  13. Early Enteral Combined with Parenteral Nutrition Treatment for Severe Traumatic Brain Injury: Effects on Immune Function, Nutritional Status and Outcomes.

    Science.gov (United States)

    Fan, Mingchao; Wang, Qiaoling; Fang, Wei; Jiang, Yunxia; Li, Liandi; Sun, Peng; Wang, Zhihong

    2016-11-20

    Objective To compare the conjoint effect of enteral nutrition (EN) and parenteral nutrition (PN) with single EN or PN on immune function, nutritional status, complications and clinical outcomes of patients with severe traumatic brain injury (STBI). Methods A prospective randomized control trial was carried out from January 2009 to May 2012 in Neurological Intensive Care Unit (NICU). Patients of STBI who met the enrolment criteria (Glasgow Coma Scale score 6~8; Nutritional Risk Screening ≥3) were randomly divided into 3 groups and were admi- nistrated EN, PN or EN+PN treatments respectively. The indexes of nutritional status, immune function, complications and clinical outcomes were examined and compared statistically. Results There were 120 patients enrolled in the study, with 40 pationts in each group. In EN+PN group, T lymthocyte subsets CD3+%, CD4+%, ratio of CD3+/CD25+, ratio of CD4+/CD8+, the plasma levels of IgA, IgM, and IgG at 20 days after nutritional treatment were significantly increased compared to the baseline(t=4.32-30.00, Pnutritional status, the serum total protein, albumin, prealbumin and hemoglobin were significantly higher in the EN (t=5.87-11.91; Pnutrition treatment. The serum prealbumin was higher in EN+PN group than that in EN group (t=2.08; Ppneumonia (27.5% vs. 50.0%; χ2= 6.39, Pnutritional status, decrease complications and improve the clinical outcomes in patients with severe traumatic brain injury.

  14. The combination of thermal dysregulation and agenesis of corpus callosum: Shapiro′s or/and reverse Shapiro′s syndrome

    Directory of Open Access Journals (Sweden)

    Yasemin Topcu

    2013-01-01

    Full Text Available Shapiro syndrome is an extremely rare condition consisting the clinical triad of recurrent hypothermia, hyperhydrosis and agenesis of the corpus callosum. On the other hand, reverse Shapiro′s sydrome is characterized periodic hyperthermia and agenesis of the corpus callosum. Here, we describe a 3.5-year-old girl with complete agenesis of corpus callosum presenting with recurrent fever and vomiting. She also had hypothermia attacks with accompanying diaphoresis. To the best of our knowledge, there is no described case with episodes of hyperthermia, hypothermia, and vomiting associated with agenesis of the corpus callosum. Recurrent vomiting may be a newly defined symptom associated with these syndromes.

  15. Lactic Acidosis Complicating Metformin and Non-Nucleoside Reverse Transcriptase Inhibitor Combination Therapy: A Smoldering Threat in the Post-HAART Era.

    Science.gov (United States)

    Ortiz-Brizuela, Edgar; Pérez-Patrigeon, Santiago; Recillas-Gispert, Claudia; Gómez-Pérez, Francisco Javier

    2015-01-01

    Dear Editor, The prevalence of type 2 diabetes (DM-2) in HIV-infected patients and the concomitant use of metformin (MTF) and non-nucleoside reverse transcriptase inhibitors (NRTI) is rising. Through inhibition of NADH dehydrogenase and DNA pol-γ, both drugs hinder oxidative phosphorylation that may lead to lactic acidosis (LA). Among NRTIs, abacavir and tenofovir have the lowest mitochondrial toxicity, with only a few LA cases reported2-4. We describe here a case of MTF-associated LA (MALA) secondary to the interaction with NRTI.

  16. Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

    Science.gov (United States)

    Mbuagbaw, Lawrence; Mursleen, Sara; Irlam, James H; Spaulding, Alicen B; Rutherford, George W; Siegfried, Nandi

    2016-12-10

    The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure

  17. Structure and dynamics of water in nonionic reverse micelles: a combined time-resolved infrared and small angle x-ray scattering study.

    Science.gov (United States)

    van der Loop, Tibert H; Panman, Matthijs R; Lotze, Stephan; Zhang, Jing; Vad, Thomas; Bakker, Huib J; Sager, Wiebke F C; Woutersen, Sander

    2012-07-28

    We study the structure and reorientation dynamics of nanometer-sized water droplets inside nonionic reverse micelles (water/Igepal-CO-520/cyclohexane) with time-resolved mid-infrared pump-probe spectroscopy and small angle x-ray scattering. In the time-resolved experiments, we probe the vibrational and orientational dynamics of the O-D bonds of dilute HDO:H(2)O mixtures in Igepal reverse micelles as a function of temperature and micelle size. We find that even small micelles contain a large fraction of water that reorients at the same rate as water in the bulk, which indicates that the polyethylene oxide chains of the surfactant do not penetrate into the water volume. We also observe that the confinement affects the reorientation dynamics of only the first hydration layer. From the temperature dependent surface-water dynamics, we estimate an activation enthalpy for reorientation of 45 ± 9 kJ mol(-1) (11 ± 2 kcal mol(-1)), which is close to the activation energy of the reorientation of water molecules in ice.

  18. Elastomers with Reversible Nanoporosity

    DEFF Research Database (Denmark)

    Szewczykowski, Piotr Przemyslaw; Andersen, K.; Schulte, Lars

    2009-01-01

    nanostructure and displays liquid-filled cavities. Upon several cycles of swelling and drying the cavities open and close in a reversible fashion. When exposed to a nonsolvent, the material remains collapsed. This discriminating behavior of liquid-material interaction holds potential for the use...

  19. Detection and differentiation of Japanese encephalitis virus genotype I and genotype III by reverse transcription loop-mediated isothermal amplification combined with restriction fragment length polymorphism.

    Science.gov (United States)

    Zhang, Liang; Cao, Sanjie; Wu, Rui; Zhu, Shuquan; Liu, Hanyang; Yuan, Lei; Shi, Shuangyan; Zhang, Dan; Huang, Xiaobo; Wen, Xintian; Wen, Yiping; Yan, Qigui; Huang, Yong; Ma, Xiaoping

    2015-04-01

    Japanese encephalitis (JE), which is a mosquito-borne arboviral infection, is the leading cause of viral encephalitis in Asian countries. The causative agent of JE is Japanese encephalitis virus (JEV), in which the predominant genotype has changed from genotype III (G III) to genotype I (G I). However, a method for the rapid differentiation between JEV G I and G III remains unavailable. This study aimed to establish a rapid JEV genotyping method using reverse transcription loop-mediated isothermal amplification (RT-LAMP). An Spe I site, which was located in the target sequence (C gene) of JEV G III strains but not in JEV G I strains, was selected as the RT-LAMP target. After testing 64 specimens, results showed that RT-LAMP can detect and differentiate JEV G I and G III specifically. Thus, a novel RT-LAMP system for the rapid detection and differentiation of JEV G I and G III was developed successfully.

  20. Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis - A systematic review with meta-analysis and trial sequential analysis.

    Science.gov (United States)

    Sjövall, Fredrik; Perner, Anders; Hylander Møller, Morten

    2017-04-01

    To assess benefits and harms of empirical mono- vs. combination antibiotic therapy in adult patients with severe sepsis in the intensive care unit (ICU). We performed a systematic review according to the Cochrane Collaboration methodology, including meta-analysis, risk of bias assessment and trial sequential analysis (TSA). We included randomised clinical trials (RCT) assessing empirical mono-antibiotic therapy versus a combination of two or more antibiotics in adult ICU patients with severe sepsis. We exclusively assessed patient-important outcomes, including mortality. Two reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated and the risk of random errors was assessed by TSA. Thirteen RCTs (n = 2633) were included; all were judged as having high risk of bias. Carbapenems were the most frequently used mono-antibiotic (8 of 13 trials). There was no difference in mortality (RR 1.11, 95% CI 0.95-1.29; p = 0.19) or in any other patient-important outcomes between mono- vs. combination therapy. In TSA of mortality, the Z-curve reached the futility area, indicating that a 20% relative risk difference in mortality may be excluded between the two groups. For the other outcomes, TSA indicated lack of data and high risk of random errors. This systematic review of RCTs with meta-analysis and TSA demonstrated no differences in mortality or other patient-important outcomes between empirical mono- vs. combination antibiotic therapy in adult ICU patients with severe sepsis. The quantity and quality of data was low without firm evidence for benefit or harm of combination therapy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  1. The Complex Solar Polarity Reversal during Cycle 24

    Science.gov (United States)

    Gopalswamy, N.; Yashiro, S.; Akiyama, S.

    2016-10-01

    The polarity reversal at solar poles is an important event with important implications for solar magnetism, the polarity of interplanetary coronal mass ejections, and even cosmic ray modulation. The poles often do not reverse simultaneously. During the several recent cycles, the north pole reversed first, followed by the south. During cycle 24, this trend has been broken in that the south pole reversed first. The polarity reversal is typically marked by the cessation of high-latitude eruptive activities such coronal mass ejections and prominence eruptions. Even though polar prominences started appearing as early as 2011, the reversal in the north was completed only by the end of 2015. On the other hand the south polar region behaved as in previous cycles and reversed over a shorter time scale, about a year before the reversal in the north. By combining prominence eruption detected automatically (Nobeyama Radioheliograph and SDO), the polar microwave brightness (Nobeyama Radioheliograph), and the magnetic butterfly diagram (SDO and NSO) we show that the complexity can be attributed to the emergence of active regions that violated the Hale polarity rule and Joy's law. The extended period of near-zero field in the north polar region should result in very weak and delayed sunspot activity in the northern hemisphere in cycle 25, the southern hemispheric activity should start early; the amplitude will depend on how the south polar fields will evolve in the declining phase of cycle (24).

  2. Emergence of Multiple Human Cytomegalovirus Ganciclovir-Resistant Mutants with Deletions and Substitutions within the UL97 Gene in a Patient with Severe Combined Immunodeficiency

    Science.gov (United States)

    Wolf, Dana G.; Yaniv, Isaac; Ashkenazi, Shai; Honigman, Alik

    2001-01-01

    Infection with multiple ganciclovir-resistant human cytomegalovirus mutants, containing different substitutions and deletions in the UL97 gene, was found in a patient with severe combined immunodeficiency (SCID) within 3 weeks of ganciclovir therapy. A novel 11-codon deletion at positions 590 to 600 was identified. These unique findings may be related to the nature of the immunodeficiency in the SCID patient. PMID:11158760

  3. Effects of adapalene-benzoyl peroxide combination gel in treatment or maintenance therapy of moderate or severe acne vulgaris: a meta-analysis.

    Science.gov (United States)

    Zhou, Rongying; Jiang, Xian

    2014-02-01

    An antibiotic-free, fixed-dose combination gel with adapalene (A) 0.1% and benzoyl peroxide (BPO) 2.5% has been developed for treatment of acne vulgaris. To compare the clinical outcomes of A-BPO combination gel with vehicle gel for treatment or maintenance therapy of patients with acne vulgaris. An electronic search of the database PubMed (1966 to September 2012), Embase (1984 to September 2012), and Cochrane Controlled Trials Register (CENTRAL; 3rd Quarter, 2012) was undertaken to identify relevant studies. Main clinical outcomes were success rate, treatment-related adverse events (AEs), AEs leading to discontinuation, satisfaction with the effectiveness, and overall satisfaction. Six studies were finally included in this meta-analysis. The A-BPO group yielded better clinical outcomes regarding the success rate (pBPO group was comparable with that of vehicle group (p=0.09), while the A-BPO group was associated with a slightly increase in the incidence of AEs leading to discontinuation when compared with the vehicle group (p=0.02). A-BPO combination gel yields better clinical outcomes including success rate, satisfaction with the effectiveness, and overall satisfaction compared to vehicle gel, despite an increased incidence of AEs leading to discontinuation. The A-BPO combination agent most likely contributes to the treatment of moderate acne vulgaris rather than severe acne vulgaris, but it may be useful in maintenance therapy of patients with severe acne vulgaris.

  4. Combined treatment with diazepam and allopregnanolone reverses tetramethylenedisulfotetramine (TETS)-induced calcium dysregulation in cultured neurons and protects TETS-intoxicated mice against lethal seizures.

    Science.gov (United States)

    Bruun, Donald A; Cao, Zhengyu; Inceoglu, Bora; Vito, Stephen T; Austin, Adam T; Hulsizer, Susan; Hammock, Bruce D; Tancredi, Daniel J; Rogawski, Michael A; Pessah, Isaac N; Lein, Pamela J

    2015-08-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant GABAA receptor blocker. Mice receiving a lethal dose of TETS (0.15 mg/kg i.p.) are rescued from death by a high dose of diazepam (5 mg/kg i.p.) administered shortly after the second clonic seizure (∼20 min post-TETS). However, this high dose of diazepam significantly impairs blood pressure and mobility, and does not prevent TETS-induced neuroinflammation in the brain. We previously demonstrated that TETS alters synchronous Ca(2+) oscillations in primary mouse hippocampal neuronal cell cultures and that pretreatment with the combination of diazepam and allopregnanolone at concentrations having negligible effects individually prevents TETS effects on intracellular Ca(2+) dynamics. Here, we show that treatment with diazepam and allopregnanolone (0.1 μM) 20 min after TETS challenge normalizes synchronous Ca(2+) oscillations when added in combination but not when added singly. Similarly, doses (0.03-0.1 mg/kg i.p.) of diazepam and allopregnanolone that provide minimal protection when administered singly to TETS intoxicated mice increase survival from 10% to 90% when given in combination either 10 min prior to TETS or following the second clonic seizure. This therapeutic combination has negligible effects on blood pressure or mobility. Combined treatment with diazepam and allopregnanolone also decreases TETS-induced microglial activation. Diazepam and allopregnanolone have distinct actions as positive allosteric modulators of GABAA receptors that in combination enhance survival and mitigate neuropathology following TETS intoxication without the adverse side effects associated with high dose benzodiazepines. Combination therapy with a benzodiazepine and neurosteroid represents a novel neurotherapeutic strategy with potentially broad application. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. [Effects of lung protective ventilation strategy combined with lung recruitment maneuver on patients with severe burn complicated with acute respiratory distress syndrome].

    Science.gov (United States)

    Li, Xiaojian; Zhong, Xiaomin; Deng, Zhongyuan; Zhang Xuhui; Zhang, Zhi; Zhang, Tao; Tang, Wenbin; Chen, Bib; Liu, Changling; Cao, Wenjuan

    2014-08-01

    To investigate the effects of lung protective ventilation strategy combined with lung recruitment maneuver on ARDS complicating patients with severe burn. Clinical data of 15 severely burned patients with ARDS admitted to our burn ICU from September 2011 to September 2013 and conforming to the study criteria were analyzed. Right after the diagnosis of acute lung injury/ARDS, patients received mechanical ventilation with lung protective ventilation strategy. When the oxygenation index (OI) was below or equal to 200 mmHg (1 mmHg = 0. 133 kPa), lung recruitment maneuver was performed combining incremental positive end-expiratory pressure. When OI was above 200 mmHg, lung recruitment maneuver was stopped and ventilation with lung protective ventilation strategy was continued. When OI was above 300 mmHg, mechanical ventilation was stopped. Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, variables of blood gas analysis (pH, PaO2, and PaCO2) were obtained by blood gas analyzer, and the OI values were calculated; hemodynamic parameters including heart rate, mean arterial pressure (MAP), central venous pressure (CVP) of all patients and the cardiac output (CO), extravascular lung water index (EVLWI) of 4 patients who received pulse contour cardiac output (PiCCO) monitoring were monitored. Treatment measures and outcome of patients were recorded. Data were processed with analysis of variance of repeated measurement of a single group and LSD test. (1) Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the levels of PaO2 and OI of patients were respectively (77 ± 8), (113 ± 5), (142 ± 6) mmHg, and (128 ± 12), (188 ± 8), (237 ± 10) mmHg. As a whole, levels of PaO2 and OI changed significantly at different time points (with F values respectively 860. 96 and 842. 09, P values below

  6. Large-scale electricity storage utilizing reversible solid oxide cells combined with underground storage of CO2 and CH4

    DEFF Research Database (Denmark)

    Jensen, Søren Højgaard; Graves, Christopher R.; Mogensen, Mogens Bjerg

    2015-01-01

    , but unfortunately it is limited to mountainous regions and therefore difficult to expand. Emerging technologies like adiabatic compressed air energy storage (ACAES) or storage using conventional power-to-gas (P2G) technology combined with underground gas storage can be more widely deployed, but unfortunately...

  7. Amine modified graphene as reversed-dispersive solid phase extraction materials combined with liquid chromatography-tandem mass spectrometry for pesticide multi-residue analysis in oil crops.

    Science.gov (United States)

    Guan, Wenbi; Li, Zhuonan; Zhang, Hongyan; Hong, Huijie; Rebeyev, Natalie; Ye, Yong; Ma, Yongqiang

    2013-04-19

    Amine modified graphene is successfully synthesized via a one-pot solvothermal reaction between graphene oxide and ammonia water, methylamine or n-butyl amine. The presence of amine groups in graphene is identified by Fourier-transform infrared spectrometry, X-ray photoelectron spectroscopy and an X-ray diffractometer. The ability of amine modified graphene to cleanup fatty acids and other interfering substances from acetonitrile extracts of oil crops has been evaluated. It is found that the resulting CH3NH-G exhibits the best performance in interfering substances removal. Meanwhile, a multi-residue method is validated on 28 representative pesticide residues in four oil crops (rapeseed, peanut, sesame seeds and soybean). This method is based on modified QuEChERS sample preparation with CH3NH-G as reversed-dispersive solid phase extraction material and liquid chromatography-tandem mass spectrometry. Use of matrix-matched standards provides acceptable results for most pesticides with overall average recoveries between 70.5 and 100% and consistent RSDs70% recovery. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-β and cerebrovascular pathology.

    Directory of Open Access Journals (Sweden)

    Panayiota Papadopoulos

    Full Text Available Animal models of Alzheimer's disease (AD are invaluable in dissecting the pathogenic mechanisms and assessing the efficacy of potential new therapies. Here, we used the peroxisome proliferator-activated receptor gamma agonist pioglitazone in an attempt to rescue the pathogenic phenotype in adult (12 months and aged (>18 months bitransgenic A/T mice that overexpress a mutated human amyloid precursor protein (APPSwe,Ind and a constitutively active form of transforming growth factor-β1 (TGF-β1. A/T mice recapitulate the AD-related cognitive deficits, amyloid beta (Aβ and cerebrovascular pathologies, as well as the altered metabolic and vascular coupling responses to increased neuronal activity. Pioglitazone normalized neurometabolic and neurovascular coupling responses to sensory stimulation, and reduced cortical astroglial and hippocampal microglial activation in both age groups. Spatial learning and memory deficits in the Morris water maze were not rescued by pioglitazone, but reversal learning was improved in the adult cohort notwithstanding a progressing Aβ pathology. While pioglitazone preserved the constitutive nitric oxide synthesis in the vessel wall, it unexpectedly failed to restore cerebrovascular reactivity in A/T mice and even exacerbated the dilatory deficits. These data demonstrate pioglitazone's efficacy on selective AD hallmarks in a complex AD mouse model of comorbid amyloidosis and cerebrovascular pathology. They further suggest a potential benefit of pioglitazone in managing neuroinflammation, cerebral perfusion and glucose metabolism in AD patients devoid of cerebrovascular pathology.

  9. Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments

    Energy Technology Data Exchange (ETDEWEB)

    Boleda, Ma Rosa [AGBAR-Aiguees de Barcelona, Gral Batet 5-7, 08028 Barcelona (Spain); Galceran, Ma Teresa [University of Barcelona, Department Analytical Chemistry, Av. Diagonal 647, 08028 Barcelona (Spain); Ventura, Francesc, E-mail: fventura@agbar.es [AGBAR-Aiguees de Barcelona, Gral Batet 5-7, 08028 Barcelona (Spain)

    2011-06-15

    The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies {>=}94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. - Highlights: > The presence of pharmaceuticals and drugs of abuse in surface water was demonstrated. > Elimination in both potabilization processes reached levels >99% for most compounds. > Four pharmaceuticals and three drugs of abuse survived the potabilization process. - The efficiency of potabilization processes to eliminate or transform pharmaceuticals and illicit drugs is evaluated.

  10. Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments.

    Science.gov (United States)

    Boleda, M A Rosa; Galceran, M A Teresa; Ventura, Francesc

    2011-06-01

    The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies ≥ 94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Treatment with a combination of ginger, L-citrulline, muira puama and Paullinia cupana can reverse the progression of corporal smooth muscle loss, fibrosis and veno-occlusive dysfunction in the aging rat.

    Science.gov (United States)

    Ferrini, Monica G; Hlaing, Su M; Chan, Andre; Artaza, Jorge N

    2015-06-01

    Aging associated erectile dysfunction is characterized within the corpora by a progressive apoptosis of the smooth muscle cells and their replacement by collagen. Nitric oxide from iNOS has been shown to inhibit these histological changes in the corpora while PDE5 inhibitors as well as certain nutraceuticals such as ginger, paullinia cupana, muira puama and L-citrulline are known to enhance the effects of NO. We evaluated whether the daily oral administration for 2 months with a combination of ginger, paullinia cupana, muira puama and L-citrulline (COMP-4) can effectively delay the ongoing corporal fibrosis, smooth muscle cell apoptosis and cavernosal veno-occlusive dysfunction (CVOD) seen in middle aged rats similar to that seen with tadalafil. 10 Month old Fisher 344 rats were treated or not for two months with COMP-4, tadalafil or a combination of tadalafil plus COMP-4. CVOD was determined by dynamic infusion cavernosometry. Penile sections of the corpora cavernosa were subjected to Masson trichrome staining to evaluate fibrosis and immunohistochemistry for desmin as a marker of smooth muscle content and inducible nitric oxide synthase (iNOS) followed by image analysis. Oxidative stress levels were determined by GSH/GSSG ratio in whole blood. a decline in the non-treated rat's erectile function is evident by 10-12 months of age and is accompanied by a decrease in the corporal smooth muscle content determined by desmin expression and an increase in corporal fibrosis. The daily treatment for two months with COMP-4 reverses this process by reducing systemic oxidative stress and increasing desmin and iNOS expression, similar to that seen with tadalafil or the combination of COMP-4 plus tadalafil. An oral combination of ginger, muira puama, Paullinia cupana and L-citrulline seems to be as effective as daily PDE5 inhibitor therapy in either delaying or reversing the onset of the histological and functional characteristics of aging related erectile dysfunction.

  12. Reversible dysphasia and statins.

    Science.gov (United States)

    Davies, Gordon Robert Wyndham

    2012-04-01

    This paper presents a case of reversible dysphasia occurring in a patient prescribed atorvastatin in combination with indapamide. A milder dysphasia recurred with the prescription of rosuvastatin and was documented on clinical examination. This resolved following cessation of rosuvastatin. The case highlights both a need for a wider understanding of potential drug interactions through the CYP 450 system and for an increased awareness, questioning and reporting of drug side-effects.

  13. Severe Combined Immunodeficiency (For Parents)

    Science.gov (United States)

    ... system . These disorders lead to reduced or malfunctioning T- and B-lymphocytes, the specialized white blood cells made in the bone marrow and the thymus gland to fight infection. When the immune system doesn' ...

  14. Combination ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) on the treatment of severe acne.

    Science.gov (United States)

    Yin, Rui; Lin, Lin; Xiao, Yan; Hao, Fei; Hamblin, Michael R

    2014-03-01

    Scarring is a very common complication of severe acne and is difficult to treat by conventional methods. 5-Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a novel treatment for improving acne lesions. Fractional laser resurfacing is a promising treatment for scar treatment because of its unique ability to stimulate the wound healing response and its depth of penetration. To evaluate the efficacy of combination therapies of ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) for scarring lesions in severe acne patients. A prospective, single-arm, pilot study. Forty subjects with severe acne were treated with 15% ALA-PDT for four times at 10-day intervals. They then received ablative fractional Er:YAG laser treatment five times at 4-week intervals. Three independent investigators evaluated subject outcomes at 1, 3, 6, and 12 months post-treatment (primary outcome); patients also provided self-assessments of improvement (secondary outcome). Significant reductions in acne score (P acne inflammatory lesions), 80% overall improvement in acne scars. After 12 months, most of subjects had improved hypertrophic/atrophic scars (good to excellent in 85%) and no one had recurrent acne inflammatory lesions. Patient self-evaluation also revealed good to excellent improvements (on average) in acne lesions and scarring, with significant improvements in self-esteem after 6 months post-treatment. PDT can control the inflammation and improve the severity of acne lesions. Fractional resurfacing is a promising new treatment modality for scars by stimulating wound healing and remodeling. The combination therapy is a promising option for severe acne to prevent and improve car formation. © 2014 Wiley Periodicals, Inc.

  15. Combination ALA-PDT and Ablative Fractional Er:YAG Laser (2,940 nm) on the Treatment of Severe Acne

    Science.gov (United States)

    Yin, Rui; Lin, Lin; Xiao, Yan; Hao, Fei; Hamblin, Michael R.

    2014-01-01

    Background Scarring is a very common complication of severe acne and is difficult to treat by conventional methods. 5-Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a novel treatment for improving acne lesions. Fractional laser resurfacing is a promising treatment for scar treatment because of its unique ability to stimulate the wound healing response and its depth of penetration. Objective To evaluate the efficacy of combination therapies of ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) for scarring lesions in severe acne patients. Methods A prospective, single-arm, pilot study. Forty subjects with severe acne were treated with 15% ALA-PDT for four times at 10-day intervals. They then received ablative fractional Er:YAG laser treatment five times at 4-week intervals. Three independent investigators evaluated subject outcomes at 1, 3, 6, and 12 months post-treatment (primary outcome); patients also provided self-assessments of improvement (secondary outcome). Results Significant reductions in acne score (P<0.01) were obtained at follow-up visits after 1, 3, 6, and 12 months. After 6 month, the lesions showed overall improvement in all of subjects (good to excellent in acne inflammatory lesions), 80% overall improvement in acne scars. After 12 months, most of subjects had improved hypertrophic/atrophic scars (good to excellent in 85%) and no one had recurrent acne inflammatory lesions. Patient self-evaluation also revealed good to excellent improvements (on average) in acne lesions and scarring, with significant improvements in self-esteem after 6 months post-treatment. Conclusions PDT can control the inflammation and improve the severity of acne lesions. Fractional resurfacing is a promising new treatment modality for scars by stimulating wound healing and remodeling. The combination therapy is a promising option for severe acne to prevent and improve car formation. PMID:24391075

  16. Successful reversal of acute vascular rejection and cyclosporine-associated nephrotoxicity in renal allograft with combined sirolimus and mycophenolate mofetil as immunotherapy.

    Science.gov (United States)

    Ołdakowska-Jedynak, U; Paczek, L; Mucha, K; Foroncewicz, B; Perkowska-Ptasińska, A

    2006-01-01

    Cyclosporine (CsA) has substantially improved patient and graft survival rates in solid organ transplantation. In clinical studies, sirolimus has been shown to be as effective as CsA to maintain survival of renal and cardiac allografts without causing nephrotoxicity. Herein we describe a patient with biopsy-proven CsA-associated nephrotoxicity and refractory renal allograft rejection who was converted from steroids, CsA, and azathioprine to steroids, sirolimus (RAPA), and low-dose mycophenolate mofetil (MMF). The follow-up period was 60 months. We observed substantial improvement, even normalization in renal function. Our patient did not give consent to repeat biopsy after conversion. We also observed a beneficial effect of CsA withdrawal on blood pressure control. The spectrum of adverse events induced by sirolimus seemed to be mild relative to the potency of the immunosuppressive effect. The excellent response to combined RAPA and MMF in this patient was probably due to "concerted actions" of these agents on both B- and T-cell functions. The combination enhanced therapeutic efficacy while minimizing the toxicity of individual drugs used in the regimen. These findings suggest that sirolimus, when used as a base therapy in combination with low-dose MMF in a renal allograft recipient, may be an alternative to CsA-based therapy, providing potent immunosuppression of a renal allograft. Sirolimus administration facilitated steroids dose reduction.

  17. The standardized BHH10 extract, a combination of Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, reverses bone mass and metabolism in a rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Huh, Jeong-Eun; Kim, Soo-Jeong; Kang, Jung-Won; Nam, Dong-Woo; Choi, Do-Young; Park, Dong-Suk; Lee, Jae-Dong

    2015-01-01

    Jasin-hwan-gagambang (BHH10), a modified prescription of Jasin-hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)-induced rats. Sprague-Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17β-estradiol (E2). BHH10 treatment significantly inhibited OVX-induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C-telopeptide type 1 collagen, and bone morphogenetic protein-2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10-treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN-treated or E2-treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Combined effects of potassium chloride and ethanol as mobile phase modulators on hydrophobic interaction and reversed-phase chromatography of three insulin variants.

    Science.gov (United States)

    Johansson, Karolina; Frederiksen, Søren S; Degerman, Marcus; Breil, Martin P; Mollerup, Jørgen M; Nilsson, Bernt

    2015-02-13

    The two main chromatographic modes based on hydrophobicity, hydrophobic interaction chromatography (HIC) and reversed-phase chromatography (RPC), are widely used for both analytical and preparative chromatography of proteins in the pharmaceutical industry. Despite the extensive application of these separation methods, and the vast amount of studies performed on HIC and RPC over the decades, the underlying phenomena remain elusive. As part of a systematic study of the influence of mobile phase modulators in hydrophobicity-based chromatography, we have investigated the effects of both KCl and ethanol on the retention of three insulin variants on two HIC adsorbents and two RPC adsorbents. The focus was on the linear adsorption range, separating the modulator effects from the capacity effects, but some complementary experiments at higher load were included to further investigate observed phenomena. The results show that the modulators have the same effect on the two RPC adsorbents in the linear range, indicating that the modulator concentration only affects the activity of the solute in the mobile phase, and not that of the solute-ligand complex, or that of the ligand. Unfortunately, the HIC adsorbents did not show the same behavior. However, the insulin variants displayed a strong tendency toward self-association on both HIC adsorbents; on one in particular. Since this causes peak fronting, the retention is affected, and this could probably explain the lack of congruity. This conclusion was supported by the results from the non-linear range experiments which were indicative of double-layer adsorption on the HIC adsorbents, while the RPC adsorbents gave the anticipated increased tailing at higher load. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. [Clinical Efficacy of Haploidentical Allo-HSCT of Reduced Intensity Preconditioning Combined with Induced Immune Tolerance after Transplantation for Severe Aplastic Anemia].

    Science.gov (United States)

    Guo, Zhi; Chen, Hui-Ren; Liu, Xiao-Dong; Yang, Kai; Lou, Jing-Xing; Zhang, Yuan; Chen, Peng; He, Xue-Peng

    2016-12-01

    To investigate the efficacy and safety of haploidentical allo-HSCT in combination of reduced intensity preconditioning combined with cyclophosphamid (CTX)-induced immune tolerance after transplanitation for treatment of severe aplastic anemia (SAA). A total of 15 patients with SAA received the haploidentical allo-HSCT of reduced intensity preconditioning combined with CTX-induced immune tolerance after transplartation in the General hospital of Beijing military command of chinese PLA from June 2012 to December 2014. The reduced intensity preconditioning regimen consisted of CTX, fludarabine, busulfex and amti-lymphocyte immunoglobin; the immune tolerance was induced with CTX (50 mg/kg·d) on day 3 after transplantation; the HSC donors were father and mother of patients. The GVHD was prevented by inmunosuppression consisted of cyclosporine A(CsA), methotrexate and tacrolimus. The aduvese reaction and disease-free survival (DFS) were observed in all the patients. All the SAA patients achieved hematopoietic reconstitution with 100% donor hematopoiesis, and all the T lymphocyte subsets increased. Out of 15 patients, 3 cases died of complication, and the DFS rate was 80% with a median follow-up of 19.8 month (6-36 months). The haploidentical allo-HSCT of reduced intensity preconditioning combined with CTX-induced immune tolerance after transplantation is safet and effective for SAA patients, that may be applied to clinical therapy.

  20. Game-based combined cognitive and neurofeedback training using Focus Pocus reduces symptom severity in children with diagnosed AD/HD and subclinical AD/HD.

    Science.gov (United States)

    Johnstone, Stuart J; Roodenrys, Steven J; Johnson, Kirsten; Bonfield, Rebecca; Bennett, Susan J

    2017-06-01

    Previous studies report reductions in symptom severity after combined working memory (WM) and inhibitory control (IC) training in children with AD/HD. Based on theoretical accounts of the role of arousal/attention modulation problems in AD/HD, the current study examined the efficacy of combined WM, IC, and neurofeedback training in children with AD/HD and subclinical AD/HD. Using a randomized waitlist control design, 85 children were randomly allocated to a training or waitlist condition and completed pre- and post-training assessments of overt behavior, trained and untrained cognitive task performance, and resting and task-related EEG activity. The training group completed twenty-five sessions of training using Focus Pocus software at home over a 7 to 8-week period. Trainees improved at the trained tasks, while enjoyment and engagement declined across sessions. After training, AD/HD symptom severity was reduced in the AD/HD and subclinical groups according to parents, and in the former group only according to blinded teachers and significant-others. There were minor improvements in two of six near-transfer tasks, and evidence of far-transfer of training effects in four of five far-transfer tasks. Frontal region changes indicated normalization of atypical EEG features with reduced delta and increased alpha activity. It is concluded that technology developments provide an interesting a vehicle for delivering interventions and that, while further research is needed, combined WM, IC, and neurofeedback training can reduce AD/HD symptom severity in children with AD/HD and may also be beneficial to children with subclinical AD/HD. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The research on long-term clinical effects and patients’ satisfaction of gabapentin combined with oxycontin in treatment of severe cancer pain

    Science.gov (United States)

    Chen, Dong-Liang; Li, Yu-Hong; Wang, Zhi-Juan; Zhu, Ye-Ke

    2016-01-01

    Abstract Gabapentin has been used as an adjuvant for treatment of cancer pain. Previous studies showed that opioids combined with gabapentin for management of cancer pain reduced the dosage of opioids. The objective of this study was to explore the clinical effect and patients’ satisfaction of oxycontin combined with gabapentin in treatment of severe cancer pain. After titration of morphine, 60 severe cancer patients with visual analog score (VAS) more than 7 were randomly divided into trial group (n = 30) and control group (n = 30). The control group was administered oxycontin and placebo, and the trial group was given oxycontin and gabapentin. VAS score was recorded pre- and post-treatment; while daily dose of oxycontin, daily cost of pain relief and life quality score were observed 1 week, 1 month, 2 months, 3 months, and 6 months post-treatment. We found that daily dose of oxycontin 1 month post was comparable between the 2 groups (P > 0.05). Three months post, compared with control group (58.0 ± 15.2 mg), average daily dose of oxycontin was significant lower in trial group (33.4 ± 11 mg) (P  0.05), while the incidence of nausea and vomiting (P = 0.038), and constipation (P oxycontin combined with gabapentin used in severe cancer pain management can control pain effectively, decreased the dose of oxycontin and the cost of cancer pain relief, and reduced the incidence of nausea and vomiting, and constipation, increased the life quality. PMID:27759644

  2. The research on long-term clinical effects and patients' satisfaction of gabapentin combined with oxycontin in treatment of severe cancer pain.

    Science.gov (United States)

    Chen, Dong-Liang; Li, Yu-Hong; Wang, Zhi-Juan; Zhu, Ye-Ke

    2016-10-01

    Gabapentin has been used as an adjuvant for treatment of cancer pain. Previous studies showed that opioids combined with gabapentin for management of cancer pain reduced the dosage of opioids.The objective of this study was to explore the clinical effect and patients' satisfaction of oxycontin combined with gabapentin in treatment of severe cancer pain. After titration of morphine, 60 severe cancer patients with visual analog score (VAS) more than 7 were randomly divided into trial group (n = 30) and control group (n = 30). The control group was administered oxycontin and placebo, and the trial group was given oxycontin and gabapentin. VAS score was recorded pre- and post-treatment; while daily dose of oxycontin, daily cost of pain relief and life quality score were observed 1 week, 1 month, 2 months, 3 months, and 6 months post-treatment. We found that daily dose of oxycontin 1 month post was comparable between the 2 groups (P > 0.05). Three months post, compared with control group (58.0 ± 15.2 mg), average daily dose of oxycontin was significant lower in trial group (33.4 ± 11 mg) (P  0.05), while the incidence of nausea and vomiting (P = 0.038), and constipation (P oxycontin combined with gabapentin used in severe cancer pain management can control pain effectively, decreased the dose of oxycontin and the cost of cancer pain relief, and reduced the incidence of nausea and vomiting, and constipation, increased the life quality.

  3. Efficacious and safe management of moderate to severe scalp seborrhoeic dermatitis using clobetasol propionate shampoo 0·05% combined with ketoconazole shampoo 2%: a randomized, controlled study.

    Science.gov (United States)

    Ortonne, J-P; Nikkels, A F; Reich, K; Ponce Olivera, R M; Lee, J H; Kerrouche, N; Sidou, F; Faergemann, J

    2011-07-01

    Topical antifungals and corticosteroids are the mainstay of treatment for seborrhoeic dermatitis. The short-contact clobetasol propionate 0·05% shampoo (CP) is an efficacious and safe once-daily treatment for scalp psoriasis. To evaluate the efficacy and safety of CP alone and combined with ketoconazole shampoo 2% (KC) in the treatment of moderate to severe scalp seborrhoeic dermatitis. This randomized and investigator-blinded study consisted of three phases, each lasting 4 weeks. During the treatment phase, subjects were randomized to receive KC twice weekly (K2), CP twice weekly (C2), CP twice weekly alternating with KC twice weekly (C2 + K2) or CP four times weekly alternating with KC twice weekly (C4+K2). All subjects received KC once weekly during the maintenance phase and were untreated during the follow-up phase. At the end of the treatment phase, all three CP-containing regimens were significantly more efficacious than K2 in decreasing the overall disease severity (P < 0·05). Both combination regimens were also significantly more efficacious than K2 in decreasing each individual sign of the disease (P < 0·05). While the C2 and C4 + K2 groups experienced slight worsening during the maintenance phase, the efficacy of C2 + K2 was sustained and remained the highest among all groups. All regimens were well tolerated without inducing any skin atrophy. Similarly low incidences of telangiectasia, burning and adverse events were observed among the four groups. The combination therapy of twice-weekly CP alternating with twice-weekly KC provided significantly greater efficacy than KC alone and a sustained effect in the treatment of moderate to severe scalp seborrhoeic dermatitis. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  4. Efficacy of caspofungin combined with trimethoprim/sulfamethoxazole as first-line therapy to treat non-HIV patients with severe pneumocystis pneumonia.

    Science.gov (United States)

    Zhang, Gensheng; Chen, Miaomiao; Zhang, Shufang; Zhou, Hongwei; Ji, Xiaozhen; Cai, Jiachang; Lou, Tianzheng; Cui, Wei; Zhang, Ning

    2018-02-01

    Combined treatment with caspofungin and trimethoprim/sulfamethoxazole (TMP/SMZ) as salvage therapy in non-HIV positive patients with severe pneumocystis pneumonia (PCP) yields poor outcomes. It remains unknown whether the use of this combination strategy as a first-line therapy would improve patient outcomes. The present study aimed to assess the efficacy of caspofungin combined with TMP/SMZ as a first-line therapy in non-HIV positive patients with severe PCP. A retrospective cohort study was conducted between March 2016 and February 2017. Patient clinical characteristics and outcomes were compared between two groups receiving first-line and second-line therapy respectively. In addition, similar cases from previous studies were assessed. A total of 14 patients were included in the present study (mean age, 58.79±14.41 years); including 9 patients receiving caspofungin and TMP/SMZ as a first-line therapy and 5 that received it as a second-line therapy. The overall positive response rate was 71.43% (10/14), with 88.89 (8/9) and 40.00% (2/5) in the first-line and second-line therapy groups, respectively (P=0.095). The positive response rates of patients requiring invasive mechanical ventilation differed significantly between the first-line (5/6, 83.33%) and the second-line (0/3, 0%) therapy groups (P=0.048). All-cause hospital mortality was 42.86% (6/14), with mortality rates of 33.33 (3/9) and 60.00% (3/5) in the first-line and second-line therapy groups, respectively (P=0.580). Combined with previously reported cases (n=27), the positive response rate was significantly greater in the first-line therapy group (11/12, 91.67%) than in the second-line therapy group (8/15, 53.33%, P=0.043). No significant differences were in all-cause mortality rates between the two groups (25.00 vs. 46.67%, P=0.424) were identified, despite the fact that all-course mortality in the first-line therapy group was ~50% that of the second-line therapy group. Therefore, the results of the

  5. Mumps virus encephalomyelitis in a 19-year old male patient with an undefined severe combined immunodeficiency post-haematopoietic bone marrow transplantation: a rare fatal complication.

    Science.gov (United States)

    Eyre, Toby A; Pelosi, Emanuela; McQuaid, Stephen; Richardson, Deborah; Newman, Joan; Hill, Kate; Veys, Paul; Davies, Graham; Orchard, Kim H

    2013-06-01

    We describe a rare case of fatal mumps encephalomyelitis occurring in 19-year old male following matched unrelated donor peripheral blood haematopoietic stem cell transplantation (HSCT). The indication for HSCT was for an undefined form of severe combined immunodeficiency (SCID). Molecular typing of the mumps viral RNA isolated from neural tissue indicated that the infection was acquired at the time of a mumps outbreak in England and Wales that occurred between 2004 and 2006. This case highlights the importance of considering mumps in the differential diagnosis of central nervous system infection in highly immunosuppressed patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. IL-2R{gamma} gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease

    Energy Technology Data Exchange (ETDEWEB)

    Henthorn, P.S.; Fimiani, V.M.; Patterson, D.F. [Univ. of Pennsylvania School of Veterinary Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the {gamma} chain of the IL-2 receptor (IL-2R{gamma}). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R{gamma} gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID. 37 refs., 3 figs.

  7. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  8. A functional language for describing reversible logic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal

    2012-01-01

    Reversible logic is a computational model where all gates are logically reversible and combined in circuits such that no values are lost or duplicated. This paper presents a novel functional language that is designed to describe only reversible logic circuits. The language includes high....... Reversibility of descriptions is guaranteed with a type system based on linear types. The language is applied to three examples of reversible computations (ALU, linear cosine transformation, and binary adder). The paper also outlines a design flow that ensures garbage- free translation to reversible logic...

  9. High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

    Science.gov (United States)

    Mouawad, Charbel; Haddad, Katia; Hamoui, Samar; Azar, Albert; Fajloun, Ziad; Makdissy, Nehman

    2015-01-01

    Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, PACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-γ and TNF-α contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations (Del/4G) are at high risk for the onset of CVDs. PMID:25973747

  10. Combining the effects of pulping severity and alkali concentration to optimize the lignocellulose-based AlkaPolP biorefinery concept.

    Science.gov (United States)

    Hundt, Martin; Engel, Norman; Schnitzlein, Klaus; Schnitzlein, Michael G

    2014-08-01

    Within the framework of the development of a novel lignocellulose biorefinery concept alkaline polyol pulping (AlkaPolP) of Pinus sylvestris was performed at different alkali concentrations. The obtained experimental data were used to develop simple mathematical models that allow the prediction of product yields and properties in dependence on a single parameter combining the effects of time, temperature and catalyst concentration. For this purpose the usual approach expressing the pulping severity R0 had to be complemented by the alkali concentration resulting in a modified severity factor R₀('). The found regression models in the form of functions f(R₀(')) can be used as a tool for the identification of those pulping conditions giving the desired product characteristics. Because the yields of the biorefinery products reach their maxima at different pulping conditions the optimization of the whole process turned out to be a multi-objective optimization problem. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Cost-effectiveness of combination fluticasone propionate–salmeterol 250/50 μg versus salmeterol in severe COPD patients

    Directory of Open Access Journals (Sweden)

    An

    2010-06-01

    Full Text Available Anand A Dalal1, Meaghan St Charles2, Hans V Petersen2, Melissa H Roberts2, Christopher M Blanchette2, Kathy Manavi-Zieverink31US Health Outcomes, GlaxoSmithKline, Research Triangle Park, NC, 2Division of Clinical and Outcomes Research, Lovelace Respiratory Research Institute, Kannapolis USA; 3INC Research, Raleigh; NC, USAObjective: To estimate the cost-effectiveness of fluticasone propionate–salmeterol combination (FSC compared to salmeterol for maintenance therapy in severe chronic obstructive pulmonary disease (COPD.Study design: Pooled economic analysis.Methods: We performed an economic analysis of pooled data from two randomized clinical trials (combined N = 1554 that evaluated the effect of maintenance therapy with FSC (250/50 μg twice daily or salmeterol (50 μg twice daily on exacerbation rates in patients with severe COPD. We calculated exacerbation rates and applied standardized costs to exacerbation-related health care utilization reported in the trials (office, urgent care, and emergency department visits; hospitalizations; and oral corticosteroids and antibiotics to determine cost differences between FSC and salmeterol treatment outcomes.Results: Annual rates of any exacerbation and moderate/severe exacerbation were lower in the FSC group than the salmeterol group (4.91 vs 5.78 and 1.32 vs 2.00 respectively, both P < 0.05. Total adjusted annual COPD related exacerbation and therapeutic costs were $4,842 (95% CI; $4,731–$4,952 in the FSC group and $5,066 (95% CI; $4,937–$5,195 in the salmeterol group.Conclusions: FSC combination therapy is associated with reduced risk of any exacerbation and moderate/severe exacerbation, and incurs lower annual COPD-related health care costs compared to treatment with salmeterol. This analysis demonstrates that FSC therapy may be advantageous from both a clinical and cost-benefit standpoint for patients with severe COPD.Keywords: COPD, cost-effectiveness analysis, economic, maintenance therapy

  12. Effect of sputum suction by bronchofiberoscope combined with routine anti-infective therapy on lung function and inflammatory state in patients with severe lung infection

    Directory of Open Access Journals (Sweden)

    Jian Sun

    2016-07-01

    Full Text Available Objective: To analyze the effect of sputum suction by bronchofiberoscope combined with routine anti-infective therapy on lung function and inflammatory state in patients with severe lung infection. Methods: A total of 52 patients with severe lung infection who received treatment in our hospital from January 2015 to December 2015 were selected as research subjects and were divided into observation group 26 cases and control group 26 cases according to different treatment methods. Differences in levels of lung function indexes, serum inflammation-related factors, disease severity-related indexes, JNK/SAPK and TLR2/NF-κB signaling pathways were compared between two groups. Results: FEV1, MMV, MMEF, FRC and TLC values of observation group after treatment were higher than those of control group (P<0.05; serum PAF, MIP-1毩, sTREM-1 and PCT values of observation group were lower than those of control group while APN value was higher than that of control group (P<0.05; serum ACE, NO, ET-1, SP-A and HMGB1 values of observation group were lower than those of control group while CC16 and ChE values were higher than those of control group (P<0.05; JNK, SAPK, TLR2 and NF-κB protein expression levels of observation group were lower than those of control group (P<0.05. Conclusions: Sputum suction by bronchofiberoscope combined with routine anti-infective therapy for patients with severe lung infection has positive significance in improving patients’ lung function, inhibiting systemic inflammation and other aspects.

  13. Glycolic Acid peels/azelaic Acid 20% cream combination and low potency triple combination lead to similar reduction in melasma severity in ethnic skin: results of a randomized controlled study.

    Science.gov (United States)

    Mahajan, Rahul; Kanwar, Amrinder Jit; Parsad, Davinder; Kumaran, Muthu Sendhil; Sharma, Reena

    2015-01-01

    Numerous therapeutic options have been tried in the management of melasma. This prospective randomized study was planned to assess the efficacy of low potency triple combination (TC) cream (TC-hydroquinone 2%/tretinoin 0.05%/fluocinolone 0.01%) versus glycolic acid (GA) peels/azelaic acid (AA) 20% cream (GA/AA) combination in melasma. Forty patients with melasma were recruited into this study and randomized into two groups. Group A consisting 20 patients received TC cream once a day for night time application for 3 months. Group B comprising of 20 patients received GA/AA 20% cream combination for 3 months. The disease severity was monitored with digital photography, melasma area and severity index (MASI) score, which was calculated at baseline, 6 weeks and 12 weeks, and visual analog scale (VAS) score, which was calculated at baseline and 12 weeks. Of 40 patients, 38 were completed the study. A significant reduction in MASI and VAS was recorded after 6 weeks and 12 weeks of treatment in both groups A and B (P = 0.001). However, there was no significant difference in the mean MASI scores between the two groups at baseline, 6 weeks and 12 weeks. Similarly, there was no difference in the mean VAS scores between the two groups at baseline and 12 weeks. Four patients in group A and 3 in group B experienced adverse effects such as irritation, dryness, and photosensitivity. Both low potency TC cream and GA/AA 20% cream combination are effective in treating melasma among Indian patients.

  14. Chemical restraint of captive Kinkajous Potos flavus (Schreber, 1774 (Carnivora: Procyonidae using a ketamine, xylazine and midazolam combination and reversal with yohimbine

    Directory of Open Access Journals (Sweden)

    Jesús Lescano

    2016-12-01

    Full Text Available Detailed information on the anaesthetic and cardiorespiratory effects of drug combinations used for the chemical immobilization of Kinkajous (Potos flavus is scarce.  This study assessed the effects of ketamine (2.5mg/kg, xylazine (1mg/kg and midazolam (0.5mg/kg combination in P. flavus.  Five clinically healthy adult Kinkajous of both sexes were included.  Heart rate, respiratory rate, oxygen saturation, blood pressure and body temperature were recorded at five-minute intervals for 25 minutes.  Then, animals received 0.125mg/kg of yohimbine by intramuscular injection.  Anaesthetic depth was assessed based on stimulus response and muscle tone.  Induction, immobilization, and recovery periods were recorded and qualitatively assessed based on the absence of adverse effects.  The durations of the induction, immobilization, and recovery periods were 9.42±1.73, 33.33±2.16, and 31.37±5.82 minutes.  All periods showed good quality and adequate anaesthetic depth was achieved.  Mean heart and respiratory rates were 99±20 beats/minute and 44±9 breaths/minute.  Both parameters decreased over the duration of the anaesthesia but they did not reach levels suggesting either bradycardia or bradypnea.  Mean body temperature was 37.1±1.5 0C and it also showed a decreasing trend over the duration of the anaesthesia.  Mean oxygen saturation was 92±6% and it showed a mildly increasing trend over the duration of the anesthesia.  Mean blood pressure was 129±23 mmHg and mild to moderate hypertension was observed.  No mortality occurred and no adverse effects were observed in any of the individuals during the three months following immobilization.  The assessed anaesthetic combination effectively immobilized the P. flavus individuals, provided good quality and acceptable duration of both induction and recovery periods.  It should, however, not be used in Kinkajous with either known hypertension record or pre-existing target organ disease (e

  15. Combined Fascia Iliaca and Sciatic Nerve Block for Hip Surgery in the Presence of Severe Ankylosing Spondylitis: A Case-Based Literature Review.

    Science.gov (United States)

    Chen, Lingmin; Liu, Jin; Yang, Jing; Zhang, Yanzi; Liu, Yue

    2016-01-01

    Selecting an appropriate anesthetic technique for patients with ankylosing spondylitis undergoing hip surgery is challenging because of a potentially difficult airway, the risk of cardiovascular and respiratory complications, and the technical difficulty of performing central neuraxial blocks in patients with ankylosing spondylitis. Our objective was to report a case in which combination neural blockade was used successfully in an elderly patient with ankylosing spondylitis undergoing hip fracture surgery. In addition, a literature review of the anesthetic techniques reported for these patients was conducted. A 70-year-old man with severe ankylosing spondylitis and respiratory dysfunction was scheduled for a closed intertrochanteric fracture reduction and internal fixation. Combined fascia iliaca block and parasacral sciatic nerve block were used successfully for the surgery. Postoperative analgesia was accomplished by continuous fascia iliaca block. According to the literature review, general anesthesia is the most commonly performed anesthetic technique for patients with ankylosing spondylitis undergoing hip surgeries. Special intubation techniques and cautious airway management were very important for these patients. Although both general anesthesia and central neuraxial blockade pose considerable risks to the patients, this case report suggests that combined fascia iliaca block and sciatic nerve block might be a promising option.

  16. A fixed-dose combination of memantine extended-release and donepezil in the treatment of moderate-to-severe Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Deardorff WJ

    2016-10-01

    Full Text Available William James Deardorff, George T Grossberg Department of Psychiatry, St Louis University School of Medicine, St Louis, MO, USA Abstract: Currently available therapies for the treatment of Alzheimer’s disease (AD consist of cholinesterase inhibitors (ChEIs, such as donepezil, and the N-methyl-D-aspartate receptor antagonist memantine. In December 2014, the US Food and Drug Administration approved Namzaric™, a once-daily, fixed-dose combination (FDC of memantine extended-release (ER and donepezil for patients with moderate-to-severe AD. The FDC capsule is bioequivalent to the coadministered individual drugs, and its bioavailability is similar when taken fasting, with food, or sprinkled onto applesauce. The combination of memantine and ChEIs in moderate-to-severe AD provides additional benefits to ChEI monotherapy across multiple domains and may delay the time to nursing home admission. A dedicated study of memantine ER compared to placebo in patients on a stable dose of a ChEI found statistically significant benefits on cognition and global status but not functioning. Treatment with memantine ER and donepezil is generally well tolerated, although higher doses of ChEIs are associated with more serious adverse events such as vomiting, syncope, and weight loss. Potential advantages of the FDC include a simpler treatment regimen, reduction in pill burden, and the ability to sprinkle the capsule onto soft foods. Patients who may benefit from the FDC include those with significant dysphagia, a history of poor compliance, or limited caregiver interaction. However, available evidence that these advantages would increase treatment adherence and persistence is conflicting, meaning that the added cost of switching patients from generic options to an FDC may not always be justified. Keywords: Alzheimer’s disease, cholinesterase inhibitor, donepezil, fixed-dose combination, memantine

  17. Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study.

    Science.gov (United States)

    Dréno, B; Kaufmann, R; Talarico, S; Torres Lozada, V; Rodríguez-Castellanos, M A; Gómez-Flores, M; De Maubeuge, J; Berg, M; Foley, P; Sysa-Jedrzejowska, A; Kerrouche, N; Paliargues, F; Bettoli, V

    2011-08-01

    Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first-line option in the treatment of moderate to severe acne vulgaris. To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%-BPO 2·5% (A/BPO) fixed-dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. A total of 378 subjects were randomized in a double-blind, controlled trial to receive once-daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects 'clear' or 'almost clear'), skin tolerability, adverse events and patients' satisfaction. The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P BPO group (-74·1%) than in the lymecycline with vehicle group (-56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were 'very satisfied' was significantly greater (P = 0·031). These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  18. COMBINATION OF MOLECULAR ADSORBENT RECIRCULATING SYSTEM AND RADIOIODINE FOR THE TREATMENT OF CONCURRENT HYPERTHYROIDISM AND SEVERE LIVER DYSFUNCTION: A RETROSPECTIVE COHORT STUDY.

    Science.gov (United States)

    Zhang, Qing; Guan, Yanxing; Xiang, Tianxin; Liu, Shaozheng; Chen, Qingjie; Zhang, Qing

    2017-02-01

    The treatment of hyperthyroidism associated with severe liver dysfunction (LD) is a clinical challenge, and there has been no unified examination of this problem. The objective of this study was to assess the efficacy and safety of radioiodine (131I) in combination with a molecular adsorbent recirculating system (MARS) for the treatment of hyperthyroidism complicated by severe liver LD. A total of 116 hyperthyroidism patients with concomitant LD who received MARS treatment were studied retrospectively. The patients were grouped according to whether or not they also received 131I treatment: Group 1 (59 patients) received 131I following MARS treatment, while Group 2 (57 cases) received only MARS. Clinical outcomes, including thyroid hormone levels, liver function parameters, and therapeutic efficacy were calculated. The overall response rate was significantly greater in Group 1 than in Group 2 (Phyperthyroidism complicated by severe LD was effective and safe. The use of this system could rapidly improve liver function and metabolism, allowing 131I therapy to be applied as early as possible with a shortened recovery time of liver function. ALSS = artificial liver support system ALT = alanine transaminase AST = aspartate transaminase ATD = antithyroid drugs DBil = direct bilirubin FT3 = free tri-iodothyronine FT4 = free thyroxine 131I = radioiodine INR = international normalized ratio LD = liver dysfunction MARS = molecular adsorbent recirculating system MELD = model for end-stage liver disease PT = prothrombin time TBil = total bilirubin TSH = thyroid-stimulating hormone.

  19. A proposal for a comprehensive grading of Parkinson's disease severity combining motor and non-motor assessments: meeting an unmet need.

    Directory of Open Access Journals (Sweden)

    Kallol Ray Chaudhuri

    Full Text Available Non-motor symptoms are present in Parkinson's disease (PD and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS is a validated scale that allows quantifying frequency and severity (burden of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB and to complete PD patient classification.This was an observational, cross-sectional international study of 935 consecutive patients. Using a distribution of NMSS scores by quartiles, a classification based on levels from 0 (no NMSB at all to 4 (very severe NMSB was obtained and its relation with Hoehn and Yahr (HY staging, motor and health-related quality of life scales was analyzed. Concordance between NMSB levels and grouping based on clinician's global impression of severity, using categorical regression, was determined. Disability and HRQoL predictors were identified by multiple regression models.The distribution of motor and QoL scales scores by HY and NMSB levels was significantly discriminative. The difference in the classification of cases for both methods, HY and NMSB, was significant (gamma = 0.45; ASE = 0.032. Concordance between NMSB and global severity-based levels from categorical regression was 91.8%, (kappaw = 0.97. NMS score was predictor of disability and QoL.Current clinical practice does not address a need for inclusion of non-motor scores in routine assessment of PD in spite of the overwhelming influence of NMS on disability and quality of life. Our data overcome the problems of "pure motor assessment" and we propose a combined approach with addition of NMSB levels to standard motor assessments.

  20. A Proposal for a Comprehensive Grading of Parkinson's Disease Severity Combining Motor and Non-Motor Assessments: Meeting an Unmet Need

    Science.gov (United States)

    Ray Chaudhuri, Kallol; Rojo, Jose Manuel; Schapira, Anthony H. V.; Brooks, David J.; Stocchi, Fabrizio; Odin, Per; Antonini, Angelo; Brown, Richard J.; Martinez-Martin, Pablo

    2013-01-01

    Background Non-motor symptoms are present in Parkinson's disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification. Methods This was an observational, cross-sectional international study of 935 consecutive patients. Using a distribution of NMSS scores by quartiles, a classification based on levels from 0 (no NMSB at all) to 4 (very severe NMSB) was obtained and its relation with Hoehn and Yahr (HY) staging, motor and health-related quality of life scales was analyzed. Concordance between NMSB levels and grouping based on clinician's global impression of severity, using categorical regression, was determined. Disability and HRQoL predictors were identified by multiple regression models. Results The distribution of motor and QoL scales scores by HY and NMSB levels was significantly discriminative. The difference in the classification of cases for both methods, HY and NMSB, was significant (gamma = 0.45; ASE = 0.032). Concordance between NMSB and global severity-based levels from categorical regression was 91.8%, (kappaw = 0.97). NMS score was predictor of disability and QoL. Conclusions Current clinical practice does not address a need for inclusion of non-motor scores in routine assessment of PD in spite of the overwhelming influence of NMS on disability and quality of life. Our data overcome the problems of “pure motor assessment” and we propose a combined approach with addition of NMSB levels to standard motor assessments. PMID:23468940

  1. Growth hormone-releasing effects of whole body vibration alone or combined with squatting plus external load in severely obese female subjects.

    Science.gov (United States)

    Giunta, Marialuisa; Cardinale, Marco; Agosti, Fiorenza; Patrizi, Alessandra; Compri, Emanuele; Rigamonti, Antonello E; Sartorio, Alessandro

    2012-01-01

    Whole body vibration (WBV) has been reported to exert growth hormone(GH)-releasing effects in healthy subjects. Despite the potential of WBV to positively affect body composition changes via lipolytic effects, few studies have been performed in obese subjects to date. This study evaluated the acute effects of WBV alone or in combination with squatting plus external load (WBV+S) on serum GH levels and blood lactate concentrations in 7 severely obese women (age 22 ± 5 years; BMI 39.9 ± 2.9 kg/m2). WBV and WBV+S determined a significant GH increase (mean GH peaks 5.1 ± 1.9 ng/ml, p external load. Further additional studies are required to verify the chronic effects of WBV exercise on the GH/IGF-1 system, which could represent a potentially effective approach for weight management in obese subjects.

  2. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  3. Tramadol plus metamizole combined or not with anti-inflammatory drugs is clinically effective for moderate to severe chronic pain treatment in cancer patients.

    Science.gov (United States)

    Flôr, Patrícia B; Yazbek, Karina V B; Ida, Keila K; Fantoni, Denise T

    2013-05-01

    To test the effectiveness and safety of tramadol plus metamizole combined or not with a non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe chronic neoplastic pain in dogs, and its impact on quality of life (QL). Prospective, uncontrolled, open-label, clinical study. Sixty nine client-owned dogs with multiple forms of cancer and visual analog scale (VAS) pain score ≥ 40 after receiving NSAIDs for at least 7 days. The MN group received metamizole + NSAID, MNT group received metamizole + NSAID + tramadol and MT group received metamizole + tramadol. Pain was scored by the 0 to 100 mm VAS (0 = no pain, 100 = worst pain) and analgesic therapy was considered effective if 25 mm differences in VAS scores were observed between day 0 and the follow ups. The QL was evaluated according to a 0 to 36 scoring method for dogs (0 = worst, 36 = best) and side effects were recorded. Data were registered at day 0 (baseline) and at the first and second follow ups (7 and 14 days after day 0, respectively). The MN group had less analgesia at day 7 (25%) and day 14 (42%) than MNT (59%, p = 0.0274; 76%, p = 0.0251, respectively) and MT groups (69%, p = 0.0151; 81%, p = 0.0341, respectively). The QL scores were lower in the MN group at the first (score 23) and second follow up (score 26) than in MNT (27, p = 0.0847; 30, p = 0.0002) and MT (28, p = 0.0384; 31, p = 0.0001) groups. Side effects were more commonly observed in the MN group (87%) than in MNT (24%, p metamizole combined or not with NSAID were well tolerated and clinically effective to treat moderate to severe pain in dogs with cancer and improved QL. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  4. Cytotoxic T-lymphocyte-associated protein 4-Ig effectively controls immune activation and inflammatory disease in a novel murine model of leaky severe combined immunodeficiency.

    Science.gov (United States)

    Humblet-Baron, Stéphanie; Schönefeldt, Susann; Garcia-Perez, Josselyn E; Baron, Frédéric; Pasciuto, Emanuela; Liston, Adrian

    2017-11-01

    Severe combined immunodeficiency can be caused by loss-of-function mutations in genes involved in the DNA recombination machinery, such as recombination-activating gene 1 (RAG1), RAG2, or DNA cross-link repair 1C (DCLRE1C). Defective DNA recombination causes a developmental block in T and B cells, resulting in high susceptibility to infections. Hypomorphic mutations in the same genes can also give rise to a partial loss of T cells in a spectrum including leaky severe combined immunodeficiency (LS) and Omenn syndrome (OS). These patients not only experience life-threatening infections because of immunodeficiency but also experience inflammatory/autoimmune conditions caused by the presence of autoreactive T cells. We sought to develop a preclinical model that fully recapitulates the symptoms of patients with LS/OS, including a model for testing therapeutic intervention. We generated a novel mutant mouse (Dclre1cleaky) that develops a LS phenotype. Mice were monitored for diseases, and immune phenotype and immune function were evaluated by using flow cytometry, ELISA, and histology. Dclre1cleaky mice present with a complete blockade of B-cell differentiation, with a leaky block in T-cell differentiation resulting in an oligoclonal T-cell receptor repertoire and enhanced cytokine secretion. Dclre1cleaky mice also had inflammatory symptoms, including wasting, dermatitis, colitis, hypereosinophilia, and high IgE levels. Development of a preclinical murine model for LS allowed testing of potential treatment, with administration of cytotoxic T-lymphocyte-associated protein 4-Ig reducing disease symptoms and immunologic disturbance, resulting in increased survival. These data suggest that cytotoxic T-lymphocyte-associated protein 4-Ig should be evaluated as a potential treatment of inflammatory symptoms in patients with LS and those with OS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. 23-gauge vitrectomy assisted by combined endoscopy and a wide-angle viewing system for retinal detachment with severe penetrating corneal injury: a case report

    Directory of Open Access Journals (Sweden)

    Morishita S

    2011-12-01

    Full Text Available Seita Morishita, Mihori Kita, Shin Yoshitake, Miou Hirose, Hideyasu OhDepartment of Ophthalmology, Hyogo Prefectural Amagasaki Hospital, Amagasaki, Hyogo, JapanBackground: We report a case of traumatic retinal detachment in an eye with severe corneal opacity that was successfully treated using 23 gauge (G transconjunctival vitrectomy assisted by endoscope and a wide-angle viewing system.Case presentation: A 22-year-old Japanese man was referred to our hospital with the suspicion of traumatic retinal detachment of the right eye, 1 month after an open globe eye injury due to fireworks. At the time of his first visit, his best-corrected visual acuity was hand motion in the right eye. A 23 G three port pars plana vitrectomy was conducted in combination with ophthalmic endoscope and a wide-angle viewing system. Endoscopy revealed a retinal detachment in the inferior quadrant with tiny retinal breaks. Primary reattachment of the retina was achieved by tamponade of SF6 gas. Five months after the vitrectomy, penetrating keratoplasty was performed and visual acuity recovered to 0.02. Optical coherent tomography revealed thinning of the retina, which might be the cause of the remaining poor vision.Conclusion: 23 G vitrectomy assisted by combined endoscopy and a wide-angle viewing system could be advantageous in managing visualization constraints due to penetrating trauma.Keywords: penetrating injury, vitrectomy, endoscope, wide angle viewing system, 23 gauge vitrectomy

  6. [Study of codeine-paracetamol combination treatment compared with tramadol-paracetamol in the control of moderate-to-severe low back pain].

    Science.gov (United States)

    Colini Baldeschi, G; Cobianchi, M R

    2012-06-01

    The objective of this study was to compare the analgesic efficacy and tolerability of tramadol hydrochloride compared with codeine phosphate in combination with paracetamol in patients with moderate-to-severe low back pain caused by osteoarthritis. In fact, while paracetamol is the analgesic of choice for this disease, in cases where this treatment may be ineffective, the therapeutic choice involves the addition of weak opioids. Due to the chronic nature of the disease, these drugs represent a safer alternative compared to anti-inflammatory drugs (NSAIDs) and selective inhibitors of cyclooxygenase 2 (COX-2). In the present study two combination treatments were considered: codeine-paracetamol (respectively 30 mg and 500 mg) and tramadol-paracetamol (respectively 37.5 mg and 325 mg). The study duration was 4 weeks and involved 38 patients (mean age 64.7 years). The effectiveness of the two treatments was assessed in terms of analgesic efficacy, tolerability and safety. The results recorded after a week of treatment and at the end of the study showed a difference in favour of codeine-paracetamol association which showed slightly higher values ​​in pain improvement and, above all, was better tolerated in terms of adverse events and drop out. The study, although conducted on a limited number of patients and for a relatively short time, demonstrates the greater efficacy and tolerability of the association codeine-paracetamol compared to tramadol-paracetamol.

  7. Combining MAD and CPAP as an effective strategy for treating patients with severe sleep apnea intolerant to high-pressure PAP and unresponsive to MAD.

    Directory of Open Access Journals (Sweden)

    Hsiang-Wen Liu

    Full Text Available This study aimed to determine the effect of combining positive airway pressure (PAP therapy and mandibular advancement device (MAD in patients with severe obstructive sleep apnea (OSA who were pressure intolerant for PAP and were unresponsive to MAD.This retrospective study reviewed the medical records of severe OSA patients with apnea-hypopnea index (AHI ≥ 30/hr who were diagnosed between October 1, 2008 and June 30, 2014. Patients were initially treated with 2 weeks of PAP, and those who were intolerant to high-pressure PAP (≥15 cm H2O were switched to 12 weeks of MAD, which is a monobloc designed at 75% of maximum protrusion. Patients who had high residual AHI (≥15/hr on MAD underwent 12 weeks of combination therapy (CT with MAD and CPAP and were enrolled in the present study. Enrolled subjects who completed the 12-week CT were followed-up until June 30, 2016.A total of 14 male patients were included. All three treatments effectively reduced AHI, oxygen desaturation index (ODI, and total sleep time with SpO2 <90% (% TST-SpO2<90% compared to pretreatment values. The residual AHI and ODI on CT was lower than that on MAD or PAP. The residual % TST-SpO2<90% was lower than that on MAD and similar to that on PAP. The therapeutic pressure on CT was on average 9.2 cm H2O lower than that on PAP. For the 11 patients who completed CT, only CT reduced ESS compared to pretreatment value. No treatment had significant impact on % slow wave sleep or overnight change of blood pressure. For patients who completed CT, the average usage was 5.9±1.7 hr/night at 12th week and 6.4±1.5 hr/night at a median follow-up of 36.5-months.Combining MAD and CPAP showed additive effects on reducing AHI and ODI, and lowered the therapeutic pressures.

  8. Influence of different combined severe shot peening and laser surface melting treatments on the fatigue performance of 20CrMnTi steel gear

    Energy Technology Data Exchange (ETDEWEB)

    Lv, You, E-mail: llvvyou@163.com.cn; Lei, Liqun; Sun, Lina

    2016-03-21

    In this paper, the effect of severe shot peening combined with laser melting (LSMSSP for short) on the fatigue resistance of 20CrMiTi steel gears is investigated in comparison with the effect of traditional shot peening on the fatigue resistance of the laser surface melted (LSMTSP for short) 20CrMiTi steel gear. The surface characteristics of the gear have been analyzed by a scanning electron microscope (SEM) and an X-ray diffractometer (XRD). The Forschungsstelle für Zahnräder und Getriebebau (FZG) back-to-back spur gear test rig was used for fatigue experiments. Experimental results showed that the residual stresses, full width at half maximum (FWHM), microhardness and retained austenite of the LSMSSP gears and LSMTSP gear were entirely different. Although the LSMSSP gears had higher surface roughness than the LSMTSP gear, the LSMSSP gears still had better fatigue resistance than the LSMTSP gear and laser surface melted gear. The nanocrystallized surface layer on the gear tooth flank created by severe shot peening might be a very important factor for improving the fatigue property of the LSMSSP gears.

  9. Combined Use of Systematic Conservation Planning, Species Distribution Modelling, and Connectivity Analysis Reveals Severe Conservation Gaps in a Megadiverse Country (Peru)

    Science.gov (United States)

    Fajardo, Javier; Lessmann, Janeth; Bonaccorso, Elisa; Devenish, Christian; Muñoz, Jesús

    2014-01-01

    Conservation planning is crucial for megadiverse countries where biodiversity is coupled with incomplete reserve systems and limited resources to invest in conservation. Using Peru as an example of a megadiverse country, we asked whether the national system of protected areas satisfies biodiversity conservation needs. Further, to complement the existing reserve system, we identified and prioritized potential conservation areas using a combination of species distribution modeling, conservation planning and connectivity analysis. Based on a set of 2,869 species, including mammals, birds, amphibians, reptiles, butterflies, and plants, we used species distribution models to represent species' geographic ranges to reduce the effect of biased sampling and partial knowledge about species' distributions. A site-selection algorithm then searched for efficient and complementary proposals, based on the above distributions, for a more representative system of protection. Finally, we incorporated connectivity among areas in an innovative post-hoc analysis to prioritize those areas maximizing connectivity within the system. Our results highlight severe conservation gaps in the Coastal and Andean regions, and we propose several areas, which are not currently covered by the existing network of protected areas. Our approach helps to find areas that contribute to creating a more representative, connected and efficient network. PMID:25479411

  10. Minimally Invasive Sinus Tarsi Approach With Cannulated Screw Fixation Combined With Vacuum-Assisted Closure for Treatment of Severe Open Calcaneal Fractures With Medial Wounds.

    Science.gov (United States)

    Zhang, Taiyuan; Yan, Yan; Xie, Xinmin; Mu, Weidong

    2016-01-01

    The aim of our prospective study was to investigate the clinical results and advantages of a minimally invasive sinus tarsi approach with cannulated screw fixation combined with vacuum-assisted closure for the treatment of severe open calcaneal fractures with medial wounds. A total of 31 patients (32 feet) with open calcaneal fractures who were admitted to our hospital from January 2008 to May 2013 were selected for the study and randomly divided into 2 groups: the cannulated screw group (n = 16 patients, 16 feet) and the plate group (n = 15 patients, 16 feet). The Böhler and Gissane angles were compared before and after surgery. The clinical results were evaluated using according to the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and the rate of infection. The follow-up duration for all patients ranged from 10 to 36 (mean 24) months. No statistically significant differences were found in the radiologic indicators, incidence of early postoperative complications, or American Orthopaedic Foot and Ankle Society ankle-hindfoot scores (p > .05) between the 2 groups. However, a statistically significant difference was seen in the duration of hospitalization (p vacuum-assisted closure is an effective method for the treatment of severe open calcaneal fractures with medial wounds. It provides good reduction and requires fewer days of hospitalization. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Moderate to severe acne in adolescents with skin of color: benefits of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 2.5% aqueous gel.

    Science.gov (United States)

    Eichenfield, Lawrence F; Krakowski, Andrew C

    2012-07-01

    Acne is common in adolescents and especially difficult to manage in people with color. A fixed combination of clindamycin phosphate and benzoyl peroxide (BPO) (clindamycin phosphate 1.2%/BPO 2.5% gel) was evaluated to determine its utility in treating moderate to severe acne in adolescents with skin of color. Three hundred thirty-seven adolescent acne subjects (aged 12 to BPO 2.5% gel or vehicle, once daily for 12 weeks. Efficacy and tolerability were evaluated. Data were compared with an adolescent (A) and skin of color (B) cohort from the same pivotal study enrolling 2,813 subjects. Superior mean percent reductions in inflammatory, noninflammatory, and total lesion counts were observed in subjects receiving clindamycin phosphate 1.2%/BPO 2.5% gel compared to vehicle. At week 12, clindamycin phosphate 1.2%/BPO 2.5% gel showed similar lesion reduction compared to groups A and B (PBPO 2.5% gel, assessed by investigator and subject, was superior to vehicle and comparable to that seen in groups A and B (PBPO 2.5% gel was associated with a low incidence of treatment-related AEs and a favorable cutaneous tolerability profile. Clindamycin phosphate 1.2%/BPO 2.5% gel has been shown to be effective, safe, and well tolerated in moderate to severe acne in adolescents with skin of color.

  12. Off-line combination of reversed-phase liquid chromatography and laser desorption/ionization time-of-flight mass spectrometry with seamless post-source decay fragment ion analysis for characterization of square-planar nickel(II) complexes.

    Science.gov (United States)

    Rehulka, Pavel; Popkov, Alexander; Nádvorník, Milan; Planeta, Josef; Mazanec, Karel; Chmelík, Josef

    2006-04-01

    Characterization of square-planar nickel(II) complexes of the Schiff base of (S)-N-benzylproline (2-benzoylphenyl)amide and various amino acids that are used as efficient alpha-amino acids synthons was carried out using laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) in off-line combination with liquid chromatography. A mixture of four square-planar nickel(II) complexes was separated using reversed-phase liquid chromatography (RPLC) and the separated fractions from the chromatographic run were spotted on the metal target directly from the column outlet using a lab-made sample deposition device. The separated fractions were then analyzed by LDI-TOF MS. Seamless postsource decay (sPSD) fragment ion analysis was used for their structural characterization, which made possible the confirmation of expected chemical structures of the analyzed compounds. The off-line combination of the separation by RPLC and analysis by LDI-TOF MS allowed successful separation, sensitive detection and structure elucidation of the square-planar nickel(II) complexes. Copyright (c) 2006 John Wiley & Sons, Ltd.

  13. Co-generation project for the Combined Cycle Power Plant President Juarez Rosarito and a reverse osmosis desalting plant; Proyecto de cogeneracion para la planta de ciclo combinado Presidente Juarez Rosarito y una planta desaladora de osmosis inversa

    Energy Technology Data Exchange (ETDEWEB)

    Beltran Mora, Hector; Espindola Hernandez, Salvador [Universidad NAcional Autonoma de Mexico (UNAM), Mexico, D.F. (Mexico)

    2006-11-15

    In this work a technical and economical analysis of the installation of a reverse osmosis desalting plant connected to a power station that uses the combined cycle technology under a co-generation scheme is presented: production of electricity and water. The operation program of the desalting power station will be determined by the demand of energy of the combined cycle power station; the proposal is that the desalting plant operates in the hours of low load of the power station and shuts down at the peak hours of electrical energy demand. So that this study is representative, the demand curves of electric energy of the units of combined cycle of Central President Juarez Rosarito of the Comision Federal de Electricidad (CFE) have been taken and updated the data of the reverse osmosis desalting plants that are available at the moment in the market. As basis of the study the level costs will be determined so much as the electrical energy generated by the power station of combined cycle, operating inside and outside of a co-generation scheme and the costs made level for the water produced by the reverse osmosis plant under two assumptions: the first one is buying the electrical energy from CFE and the second one considering that the CFE is the owner of the desalting plant and therefore the cost of electrical energy to desalting the plant is zero. This work shows the economic impacts on the costs of the generation of electrical energy and on those of the desalted water in a co-generation scheme. The results shown in this study can be considered for the future planning in the construction of desalting plants to supply of water in the Northwestern zones of the country where serious problems of water shortage exist. [Spanish] En este trabajo se presenta un analisis tecnico y economico de la instalacion de una planta desaladora de osmosis inversa acoplada a una central de generacion de energia electrica que utiliza la tecnologia de ciclo combinado bajo un esquema de

  14. The effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder: A randomized clinical trial.

    Science.gov (United States)

    Sepehrmanesh, Zahra; Fahimi, Hosein; Akasheh, Goudarz; Davoudi, Mohamadreza; Gilasi, Hamidreza; Ghaderi, Amir

    2017-11-01

    Different studies have been conducted to find the best adjuvant therapies for depression management. There are controversies over the effects of aspirin as an adjuvant therapy for depression. To determine the effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder. This randomized clinical trial was conducted at Kargarnejad Psychiatric Hospital in Kashan, Isfahan, Iran, from September 1, 2016 to November 1, 2016. The study participants included 100 patients with major depressive disorder who were assigned to aspirin and placebo groups by the use of computer-generated random numbers. Patients in these groups respectively received sertraline-aspirin and sertraline-placebo for eight consecutive weeks. Patients were prescribed 80 milligrams of aspirin twice a day. Also, sertraline was administered at a dose of 50-200 milligrams daily. Beck Depression Inventory was employed for depression severity assessment at four time points, namely before, two, four, and eight weeks after the beginning of the intervention. Medication side effects were also assessed eight weeks after the beginning of the intervention. Data were analyzed by SPSS version 12.0, using Chi-square and the Independent-samples t-test (α=0.05). Both groups were matched in terms of age (p=0.46), gender (p=0.539), and depression severity (p=0.509, with mean score 33.5±4.1 vs. 32.8±5.9) at baseline. However, depression scores were reduced significantly four and eight weeks after initiation of therapy just in the sertraline-aspirin group (pdepression severity among patients with major depressive disorder. Yet, further studies are needed to prove the effectiveness of aspirin and other anti-inflammatory agents in reducing depression severity. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2016082829556N1. The authors received financial support from Research Deputy of Kashan University

  15. Combined application of tenuigenin and β-asarone improved the efficacy of memantine in treating moderate-to-severe Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Chang W

    2018-03-01

    Full Text Available Wenguang Chang,1 Junfang Teng2 1Department of Neurology, Xinxiang Central Hospital, Xinxiang, Henan, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Henan, People’s Republic of China Background: Alzheimer’s disease (AD is a slowly progressive neurodegenerative disease which cannot be cured at present. The aim of this study was to assess whether the combined application of β-asarone and tenuigenin could improve the efficacy of memantine in treating moderate-to-severe AD.Patients and methods: One hundred and fifty-two patients with moderate-to-severe AD were recruited and assigned to two groups. Patients in the experiment group received β-asarone 10 mg/d, tenuigenin 10 mg/d, and memantine 5–20 mg/d. Patients in the control group only received memantine 5–20 mg/d. The Mini Mental State Examination (MMSE, Clinical Dementia Rating Scale (CDR, and Activities of Daily Living (ADL were used to assess the therapeutic effects. The drug-related adverse events were used to assess the safety and acceptability. Treatment was continued for 12 weeks.Results: After 12 weeks of treatment, the average MMSE scores, ADL scores, and CDR scores in the two groups were significantly improved. But, compared to the control group, the experimental group had a significantly higher average MMSE score (p<0.00001, lower average ADL score (p=0.00002, and lower average CDR score (p=0.030. Meanwhile, the rates of adverse events were similar between the two groups. Subgroup analysis indicated that the most likely candidates to benefit from this novel method might be the 60–74-years-old male patients with moderate AD.Conclusion: These results demonstrated that the combined application of β-asarone and tenuigenin could improve the efficacy of memantine in treating moderate-to-severe AD. The clinical applicability of this novel method showed greater promise and should be further explored. Keywords

  16. The impact of coronary artery disease severity on late survival after combined aortic valve replacement and coronary artery bypass grafting - experience of a single cardiac surgery center.

    Science.gov (United States)

    Perek, Bartłomiej; Misterski, Marcin; Stachowiak, Wojciech; Buczkowski, Piotr; Stefaniak, Sebastian; Puślecki, Mateusz; Urbanowicz, Tomasz; Budniak, Wiktor; Jemielity, Marek

    2014-12-01

    The severity of coronary artery disease (CAD) may have an impact on the outcomes of patients (pts) after aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). The aim of the study was to analyze survival after simultaneous AVR and CABG with respect to CAD severity. The study involved 143 consecutive pts (40 women and 103 men) with a mean age of 65.1 ± 7.7 years treated between 2006 and 2009. The indication for surgery was aortic stenosis accompanied by left main or three-vessel disease (group A; n = 43) and by single- or two-vessel disease (group B; n = 100). In-hospital and late mortality were analyzed. Post-discharge survival was estimated using the Kaplan-Meier method. Moreover, selected preoperative clinical and echocardiographic data as well as intraoperative variables were compared between the groups. In-hospital mortality was 4.7% in group A and 3.0% in group B (NS). The 12-month and 48-month survival probability rates were 0.88 ± 0.05 and 0.83 ± 0.06 in group A, and 0.97 ± 0.01 and 0.92 ± 0.03 in group B, respectively (p < 0.05). Patients in group A and B differed (p < 0.05) with respect to the preoperative prevalence of arterial hypertension (65.1% vs. 42.0%) and atrial fibrillation (18.6% vs. 6.0%) as well as with regard to the rate of complete revascularization (20.9% vs. 85.0%, group A and B, respectively). Coronary artery disease severity impacts long-term survival after combined AVR and CABG. Patients with left main or three-vessel disease more often undergo incomplete surgical revascularization, and this fact may be one of the predictors of an unfavorable outcome.

  17. The impact of coronary artery disease severity on late survival after combined aortic valve replacement and coronary artery bypass grafting – experience of a single cardiac surgery center

    Science.gov (United States)

    Misterski, Marcin; Stachowiak, Wojciech; Buczkowski, Piotr; Stefaniak, Sebastian; Puślecki, Mateusz; Urbanowicz, Tomasz; Budniak, Wiktor; Jemielity, Marek

    2014-01-01

    Introduction The severity of coronary artery disease (CAD) may have an impact on the outcomes of patients (pts) after aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). Aim The aim of the study was to analyze survival after simultaneous AVR and CABG with respect to CAD severity. Material and methods The study involved 143 consecutive pts (40 women and 103 men) with a mean age of 65.1 ± 7.7 years treated between 2006 and 2009. The indication for surgery was aortic stenosis accompanied by left main or three-vessel disease (group A; n = 43) and by single- or two-vessel disease (group B; n = 100). In-hospital and late mortality were analyzed. Post-discharge survival was estimated using the Kaplan-Meier method. Moreover, selected preoperative clinical and echocardiographic data as well as intraoperative variables were compared between the groups. Results In-hospital mortality was 4.7% in group A and 3.0% in group B (NS). The 12-month and 48-month survival probability rates were 0.88 ± 0.05 and 0.83 ± 0.06 in group A, and 0.97 ± 0.01 and 0.92 ± 0.03 in group B, respectively (p < 0.05). Patients in group A and B differed (p < 0.05) with respect to the preoperative prevalence of arterial hypertension (65.1% vs. 42.0%) and atrial fibrillation (18.6% vs. 6.0%) as well as with regard to the rate of complete revascularization (20.9% vs. 85.0%, group A and B, respectively). Conclusions Coronary artery disease severity impacts long-term survival after combined AVR and CABG. Patients with left main or three-vessel disease more often undergo incomplete surgical revascularization, and this fact may be one of the predictors of an unfavorable outcome. PMID:26336450

  18. The association of self-regulation with weight loss maintenance after an intensive combined lifestyle intervention for children and adolescents with severe obesity.

    Science.gov (United States)

    Halberstadt, Jutka; de Vet, Emely; Nederkoorn, Chantal; Jansen, Anita; van Weelden, Ottelien H; Eekhout, Iris; Heymans, Martijn W; Seidell, Jacob C

    2017-01-01

    Knowledge is limited on the role the ability to self-regulate plays in the long-term outcome of obesity treatment in children and adolescents with severe obesity. The purpose of this study was to determine whether the ability to self-regulate after an one year intensive, partly inpatient, combined lifestyle intervention is associated with weight loss maintenance in children and adolescents with severe obesity. One hundred twenty participants (8-19 years) with an average SDS-BMI of 3.41 and their parents/caregivers were included in an intervention study. As primary determinant of weight loss maintenance, general self-regulation ability was evaluated using two behavioral computer tasks assessing inhibitory control and sensitivity to reward. There was no association between inhibitory control at T12 and ∆SDS-BMI between T12 and T24 (β = 0.0002; CI 95% = -0.0010-0.0014; P = 0.761). There was also no relation between sensitivity to reward at T12 and ∆SDS-BMI between T12 and T24 (β = -0.0028; CI 95% = -0.0075-0.0019; P = 0.244). None of the psychosocial factors that were examined as moderators, showed a statistically significant interaction, except for parental feeding style (P = 0.023). The ability to self-regulate after an intensive, partly inpatient, multidisciplinary one year intervention for severe obesity in children and adolescents was not associated with the ability to maintain the achieved weight loss during the following year. Factors that explain the large range of long term outcomes need to be elucidated. Netherlands Trial Register (NTR1678, registered 20-Feb-2009).

  19. An In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression.

    Directory of Open Access Journals (Sweden)

    Gilles Darcis

    2015-07-01

    Full Text Available The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET bromodomain inhibitors (BETi are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC agonists (prostratin, bryostatin-1 and ingenol-B, which are known to activate NF-κB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151. Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latency-reversing agents (LRAs and that their combinations led to synergistic activation of HIV-1 expression at the viral mRNA and protein levels. Mechanistically, combined treatments led to higher activations of P-TEFb and NF-κB than the corresponding individual drug treatments. Importantly, we observed in ex vivo cultures of CD8+-depleted PBMCs from 35 cART-treated HIV-1+ aviremic patients that the percentage of reactivated cultures following combinatory bryostatin-1+JQ1 treatment was identical to the percentage observed with anti-CD3+anti-CD28 antibodies positive control stimulation. Remarkably, in ex vivo cultures of resting CD4+ T cells isolated from 15 HIV-1+ cART-treated aviremic patients, the combinations bryostatin-1+JQ1 and ingenol-B+JQ1 released infectious viruses to levels similar to that obtained with the positive control stimulation. The potent effects of these two combination treatments were already detected 24 hours post-stimulation. These results constitute the first demonstration of LRA

  20. Lassa Virus Reverse Genetics.

    Science.gov (United States)

    Martínez-Sobrido, Luis; Paessler, Slobodan; de la Torre, Juan Carlos

    2017-01-01

    The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity and mortality. To date, no licensed vaccines are available to LASV infections, and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that is only partially effective. The development of reverse genetics has provided investigators with a novel and powerful approach for the investigation of the molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV minigenome (MG) systems has allowed examining the cis- and trans-acting factors involved in genome replication and gene transcription and the identification of novel drugable LASV targets. Likewise, it is now feasible to rescue infectious recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify antiviral drugs against LASV and the implementation of novel strategies to develop live-attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art experimental procedures for implementation of LASV reverse genetics. In addition, we will briefly discuss some significant translational research developments that have been made possible upon the development of LASV reverse genetics.

  1. Clinical Evaluation of Continuous Renal Replacement Therapy in Combination with Ultrasound-Guided Percutaneous Transhepatic Gallbladder Drainage for Acute Severe Biliary Pancreatitis: a Retrospective Study

    Directory of Open Access Journals (Sweden)

    Qingyun Zhu

    2017-11-01

    Full Text Available Background/Aims: This study aimed to report the clinical efficacy of continuous renal replacement therapy (CRRT in combination with ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD (CRRT+PTGD in the treatment of acute severe biliary pancreatitis (ASBP. Methods: Between January 2010 and January 2016, 40 cases of patients with ASBP who received routine CRRT (CRRT group and 40 of those who received CRRT+PTGD (CRRT+PTGD group at the Affiliated Hospital of Qingdao University (Qingdao, China were retrospectively reviewed. Clinical (including abdominal pain remission time, gastrointestinal decompression time, Intensive Care Unit (ICU hospital stay, respirator treatment time, and mortality rate, laboratory (white blood cells [WBC], platelet [PLT], procalcitonin [PCT], C-reactive protein [CRP], total bilirubin [TBIL], alanine aminotransferase [ALT], albumin [ALB], and blood lactic acid [Lac] parameters, various critical disease scores, and incidence of complications after the treatment were compared between the two groups. Results: Compared with those in the routine CRRT group, patients in the CRRT+PTGD group exhibited significant remission of clinical symptoms (i.e. shorter abdominal pain remission time, gastrointestinal decompression time, respirator treatment time and ICU hospital stay (all P<0.05, change of laboratory parameters (WBC, PLT, PCT, CRP, TBIL, ALT (P<0.05, and improvement of various critical disease scores (P<0.05. Moreover, the variation of most of the above parameters after versus before the treatment was greater in the CRRT+PTGD group than in the CRRT group (all P<0.05. Conclusion: CRRT in combination with PTGD is more effective in the treatment of ASBP than CRRT alone.

  2. The effects of the combination of chlorhexidine/thymol- and fluoride-containing varnishes on the severity of root caries lesions in frail institutionalised elderly people.

    Science.gov (United States)

    Brailsford, S R; Fiske, J; Gilbert, S; Clark, D; Beighton, D

    2002-01-01

    To compare the clinical effects of a fluoride-containing varnish (Fluor-Protector) in combination with a chlorhexidine-containing varnish (Cervitec) on existing root caries lesions in a group of frail elderly subjects. A randomised double blind longitudinal study was utilised. Subjects (n = 102) were randomly allocated to a Test or Placebo group. All leathery and soft root caries lesions in all subjects were coated with Fluor-Protector while the lesions in the Test group were also coated with Cervitec and the lesions in the Placebo group were coated with a Placebo varnish. Treatments were repeated five times in a 12-month period. Clinical parameters associated with root caries, measurements of individual lesions and salivary levels of caries associated bacteria were made at intervals. The clinical severity of the lesions in the Test group did not change significantly during the 12-month study period. In the Placebo group the mean lesion width and lesion height and length of exposed root increased significantly and the lesions were significantly closer to the gingival margin. There were no significant changes in the salivary levels of caries-associated microorganisms after 12 months although, in both groups, there was initially a significant reduction in the salivary levels of mutans streptococci. The combination of Fluor-Protector and Cervitec is a useful, simple, quick and non-invasive method for the control and management of existing root caries lesions. The procedure could be performed by a dental hygienist and may be usefully applied in other high-risk groups including persons with Parkinson's disease, debilitating neuromuscular conditions and dry mouth from whatever cause. Copyright 2002 Elsevier Science Ltd.

  3. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa.

    Science.gov (United States)

    Hartel, Bas P; Löfgren, Maria; Huygen, Patrick L M; Guchelaar, Iris; Lo-A-Njoe Kort, Nicole; Sadeghi, Andre M; van Wijk, Erwin; Tranebjærg, Lisbeth; Kremer, Hannie; Kimberling, William J; Cremers, Cor W R J; Möller, Claes; Pennings, Ronald J E

    2016-09-01

    Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups. Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations. The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Hematologic effects of recombinant factor VIIa combined with hemoglobin-based oxygen carrier-201 for prehospital resuscitation of swine with severe uncontrolled hemorrhage due to liver injury.

    Science.gov (United States)

    Arnaud, Françoise; Hammett, Michael; Philbin, Nora; Scultetus, Anke; McCarron, Richard; Freilich, Daniel

    2008-10-01

    The combination of traumatic injury, hemorrhage, and fluid resuscitation results in consumption and dilution of coagulation factors, adversely impacting hematology outcome in trauma patients. The hemostatic effects of escalating doses of recombinant factor VIIa added to hemoglobin-based oxygen carrier-201 were assessed as prehospital fluid resuscitation in swine with severe uncontrolled hemorrhage. Swine underwent liver injury causing severe uncontrolled hemorrhage and shock. During a 4-h prehospital phase, either hypotensive or tachycardic, or both, animals were resuscitated with hemoglobin-based oxygen carrier-201 without (0x) or with escalating doses of recombinant factor VIIa [90 microg/kg (1x), 180 microg/kg (2x), or 360 microg/kg (4x)]. The animals received one initial full dose of 10 ml/kg at 15 min and up to four doses of 5 ml/kg thereafter. From 4 to 72 h (hospital phase), animals received either transfusions or isotonic saline or both as needed. Hematology profile (complete blood count), thromboelastography, in-vitro bleeding (platelet function analyzer), and coagulation (prothrombin time) were measured and the results were compared using mixed statistical models. In all groups, dilutional coagulopathy was evidenced by reduced hematocrit, platelets, and thromboelastography-maximum amplitude, and increased platelet function analyzer closure time and thromboelastography-reaction time. During the prehospital phase, hemoglobin-based oxygen carrier-201 restored hemoglobin in all groups. Recombinant factor VIIa decreased prothrombin time in recombinant factor VIIa groups compared with the hemoglobin-based oxygen carrier-201 group (P 0.05). Compared with hemoglobin-based oxygen carrier, 1x recombinant factor VIIa tended to decrease blood loss, lactate and thromboelastography-reaction time at 24 h but the 4x group increased these parameters. Platelets and thromboelastography-maximum amplitude decreased (P hemoglobin-based oxygen carrier-201 did not change

  5. Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis.

    Science.gov (United States)

    Penna, Pete; Meckfessel, Matthew H; Preston, Norman

    2014-01-01

    Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of

  6. Clinical Applications of Reverse Panoramic Radiography

    Directory of Open Access Journals (Sweden)

    Sujatha S Reddy

    2011-09-01

    Full Text Available The essence of oral and maxil-lofacial radiology is not only to be an important tool in the diagnostic assessment of dental patients but also to equip the clinician with the ability to interpret images of certain maxillocraniofacial structures of importance to dental, medical and surgical practices. Although combinations of several conven-tional x-ray projections can be adequate in a number of clinical situations, radiographic assessment of certain craniofacial structures some-times needs to be facilitated by other imaging modalities. A not-so-recent development called reverse panoramic radiography may be a useful adjuvant to such a situation, at least in the near future. It is essentially a technique where the patient is placed backwards in the panoramic machine in a reverse position in such a way that x-ray beam is directed through the patient’s face and the exit beam then passes through the patient’s head on the opposite side where it is captured on the receptor. The following manuscript is an attempt to throw light on this technique and the impact it may have on dental, medical and surgical practices. The advantages and disadvantages of reverse panoramic radiography and it’s comparison to conventional panoramic radiographs and other skull views are also dis-cussed.

  7. Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Suellen M. Andrade

    2017-01-01

    Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

  8. Keratinocyte antiviral response to Poly(dA:dT stimulation and papillomavirus infection in a canine model of X-linked severe combined immunodeficiency.

    Directory of Open Access Journals (Sweden)

    Jennifer A Luff

    Full Text Available X-linked severe combined immunodeficiency (XSCID is caused by a genetic mutation within the common gamma chain (γc, an essential component of the cytokine receptors for interleukin (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. XSCID patients are most commonly treated with bone marrow transplants (BMT to restore systemic immune function. However, BMT-XSCID humans and dogs remain at an increased risk for development of cutaneous papillomavirus (PV infections and their associated neoplasms, most typically cutaneous papillomas. Since basal keratinocytes are the target cell for the initial PV infection, we wanted to determine if canine XSCID keratinocytes have a diminished antiviral cytokine response to poly(dA:dT and canine papillomavirus-2 (CPV-2 upon initial infection. We performed quantitative RT-PCR for antiviral cytokines and downstream interferon stimulated genes (ISG on poly(dA:dT stimulated and CPV-2 infected monolayer keratinocyte cultures derived from XSCID and normal control dogs. We found that XSCID keratinocytes responded similarly to poly(dA:dT as normal keratinocytes by upregulating antiviral cytokines and ISGs. CPV-2 infection of both XSCID and normal keratinocytes did not result in upregulation of antiviral cytokines or ISGs at 2, 4, or 6 days post infection. These data suggest that the antiviral response to initial PV infection of basal keratinocytes is similar between XSCID and normal patients, and is not the likely source for the remaining immunodeficiency in XSCID patients.

  9. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

    Directory of Open Access Journals (Sweden)

    Robert S B Clark

    Full Text Available There are no therapies shown to improve outcome after severe traumatic brain injury (TBI in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children.IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8 requiring an externalized ventricular drain for measurement of intracranial pressure (ICP. Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses, or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS score was assessed at 3 months.There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM. Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups.Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children

  10. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

    Science.gov (United States)

    Clark, Robert S B; Empey, Philip E; Bayır, Hülya; Rosario, Bedda L; Poloyac, Samuel M; Kochanek, Patrick M; Nolin, Thomas D; Au, Alicia K; Horvat, Christopher M; Wisniewski, Stephen R; Bell, Michael J

    2017-01-01

    There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. Clinical

  11. Reversibility of chronic airflow obstruction

    NARCIS (Netherlands)

    Postma, Dirkje Sjoukje

    1984-01-01

    This thesis deals with variations in airway diameter in patients with chronic, partly reversible airflow obstruction. The patients studied in this thesis have been addressed in the literature with terms as CAO, COPD, CNSLD. The confusion caused by combining patients in one descriptive term, e.g.

  12. Direct extraction of urinary analytes from undeveloped reversed-phase thin layer chromatography plates using a solvent gradient combined with on-line electrospray ionisation ion mobility-mass spectrometry.

    Science.gov (United States)

    Devenport, Neil A; Reynolds, James C; Weston, Daniel J; Wilson, Ian D; Creaser, Colin S

    2012-08-07

    The direct extraction of urinary analytes deposited on reversed-phase thin-layer chromatography (RP-TLC) plates is demonstrated using a solvent gradient extraction procedure without prior chromatographic development. The surface sample probe TLC-MS interface used for the gradient extraction is compared to direct loop injection into the electrospray ion source for biofluid profiling. The gradient elution is shown to enhance ion intensities, as urinary salts are eluted in aqueous formic acid in the early part of the gradient reducing ion suppression. The retention of urinary components on the C18 RP-TLC plate was confirmed by monitoring analyte responses with, and without, an aqueous wash phase prior to the solvent gradient extraction. The use of gradient elution allows fractionation of the complex biological matrix as a result of differential retention of urine components on the undeveloped RP-TLC plate. The direct gradient analysis of TLC plates has also been combined with ion mobility-mass spectrometry to further resolve the complex urinary profile and identify co-eluting compounds.

  13. Comparison of distal soft-tissue procedures combined with a distal chevron osteotomy for moderate to severe hallux valgus: first web-space versus transarticular approach.

    Science.gov (United States)

    Park, Yu-Bok; Lee, Keun-Bae; Kim, Sung-Kyu; Seon, Jong-Keun; Lee, Jun-Young

    2013-11-06

    There are two surgical approaches for distal soft-tissue procedures for the correction of hallux valgus-the dorsal first web-space approach, and the medial transarticular approach. The purpose of this study was to compare the outcomes achieved after use of either of these approaches combined with a distal chevron osteotomy in patients with moderate to severe hallux valgus. One hundred and twenty-two female patients (122 feet) who underwent a distal chevron osteotomy as part of a distal soft-tissue procedure for the treatment of symptomatic unilateral moderate to severe hallux valgus constituted the study cohort. The 122 feet were randomly divided into two groups: namely, a dorsal first web-space approach (group D; sixty feet) and a medial transarticular approach (group M; sixty-two feet). The clinical and radiographic results of the two groups were compared at a mean follow-up time of thirty-eight months. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scale hallux metatarsophalangeal-interphalangeal scores improved from a mean and standard deviation of 55.5 ± 12.8 points preoperatively to 93.5 ± 6.3 points at the final follow-up in group D and from 54.9 ± 12.6 points preoperatively to 93.6 ± 6.2 points at the final follow-up in group M. The mean hallux valgus angle in groups D and M was reduced from 32.2° ± 6.3° and 33.1° ± 8.4° preoperatively to 10.5° ± 5.5° and 9.9° ± 5.5°, respectively, at the time of final follow-up. The mean first intermetatarsal angle in groups D and M was reduced from 15.0° ± 2.8° and 15.3° ± 2.7° preoperatively to 6.5° ± 2.2° and 6.3° ± 2.4°, respectively, at the final follow-up. The clinical and radiographic outcomes were not significantly different between the two groups. The final clinical and radiographic outcomes between the two approaches for distal soft-tissue procedures were comparable and equally successful. Accordingly, the results of this study suggest that the medial transarticular

  14. Managing Reverse Logistics or Reversing Logistics Management?

    OpenAIRE

    Brito, Marisa

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

  15. Short-term effects of combination of several physiotherapy methods on the respiratory function - a case report of adolescent idiopathic scoliosis.

    Science.gov (United States)

    Wnuk, Bartosz; Frackiewicz, Joanna; Durmala, Jacek; Czernicki, Krzysztof; Wadolowski, Karol

    2012-01-01

    The aim of the study was to evaluate the positive effects of combination of several physiotherapy methods on the respiratory function on example of a case report. 14 years old girl with an adolescent idiopathic scoliosis (AIS), right thoracic (primary curve, Cobb angle = 40°, AVR = 12°) and left lumbar (secondary curve, Cobb angle = 33°, AVR = 24°) participated in the study. She was 2 years after menarche. She underwent stationary (in-patient) treatment for 3 weeks with use of standard medical care (DoboMed). Treatment also included manual therapy (OMT Kaltenborn-Evjenth) and Dynamic Brace System (DBC) device, produced by Meditrack. Then she continued exercises at home. Respiratory system function was analyzed with use of SpiroPro electronic spirometer (Jaeger) and the strength of respiratory muscles with use of portable digital pressure meter equipped with the Omega PX 25 ± 35 kPa pressure transducer. Range of movement of the spine was examined with Rippstein V plurimeter, angle of apical trunk rotation (ATR) with the Bunnell scoliometer. Measurement was performed 4 times: before treatment, after one week and 3 weeks after the beginning of the treatment and 3 months after finalization of the treatment period. Examination showed that DoboMed medical care treatment, manual therapy and use of DBC device in period of 3 weeks caused improvement of respiratory parameters (MIP - maximal inspiration pressure by 6.7%; MEP - maximal expiratory pressure by 12.6%, PEF - peak expiratory flow by 16.1%). Spinal range of lateral movement and angle of apical trunk rotation has also improved. In short term treatment, the manual therapy aided with DBC system has improved the respiratory parameters and trunk morphology values. Such a composition of various physiotherapy methods can help to conduct further specialized exercises of DoboMed method.

  16. Effects of NM-3 on lymphatic vessel density and vascular endothelial growth factor of colon cancer in orthotopic implantation model of a severe combined immune deficiency mice

    Directory of Open Access Journals (Sweden)

    Jin-Shui Zhu

    2010-12-01

    Full Text Available The molecular mechanisms involved colon cancer tumorigenesis and development of colon cancer remain unclear. The aim of this study is to explore the inhibitive effects of NM-3 on lymphatic vessel density and vascular endothelial growth factor of micrometastatic lesion of orthotopic implantated colon cancer in the severe combined immune deficiency (SCID nude mice. Human colon cancer SW1116 cells were orthotopically implantated into the colon of the nude mice. Twenty-eight SCID nude mice were randomly divided into four groups (7 mice for each group after one week feeding and then the nude mice were treated with carboplatin and NM-3 via intraperitoneal injection twice a week for 8 weeks. The mice were sacrificed after 8 weeks and the vascular endothelial growth factor-C (VEGF-C, VEGF-D, VEGF-R-3 and lymphatic vessel density (LVD were analyzed using immunohistochemistry staining assay. LVD in NM-3 treated mice was significantly lower than that of control (normal saline treated mice. The expression of VEGF-C, VEGF-D, and VEGF-R-3 and the expression of mRNA of VEGF-C, VEGF-D, and VEGF-R-3 in NM-3 treated mice were significantly lower than that of control mice. The NM-3 inhibited the growth of colon cancer in the SCID mice of orthotopic implantatation model, and this effect may be related to the inhibitive effects of NM-3 on the lymphangiogenesis and vascular endothelial growth factor in colon cancer. NM-3 and carboplatin played a synergistic role in inhibiting lymphangiogenesis of human colon cancer in SCID nude mice and the further investigation of molecular mechanisms involved in colon cancer metastasis will provide an important evidence for understanding of lymphangiogenesis of human colon cancer.

  17. Two unique mutations in the interleukin-2 receptor gamma chain gene (IL2RG) cause X-linked severe combined immunodeficiency arising in opposite parental germ lines

    Energy Technology Data Exchange (ETDEWEB)

    Puck, J.M.; Pepper, A.E. [National Institutes of Health, Bethesda, MD (United States)

    1994-09-01

    The gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human X13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). 27 X-linked SCID mutations have been found in our laboratory. Single strand conformation polymorphism (SSCP) analysis of genomic DNA using primers flanking each of the 8 exons was followed by direct sequencing of abnormally migrating fragments from SCID patients and family members. A 9 bp in-frame duplication insertion was found in IL2RG exon 5 of a patient from a large X-linked SCID pedigree; the resulting duplication of 3 extracellular amino acids, including the first tryptophan of the {open_quotes}WSXWS{close_quotes} cytokine binding motif, is predicted to disrupt interaction of the cytokine receptor chain with its ligand. Genetic linkage studies demonstrated that the grandmaternal X chromosome associated with SCID was contributed to 3 daughters, 2 obligate carriers and 1 woman of unknown status. However, this grandmother`s genomic DNA did not contain the insertion mutation, nor did she have skewed X-chromosome inactivation in her lymphocytes. That both obligate carrier daughters, but not the third daughter, had the insertion proved the grandmother to be a germline mosaic. A second proband had X-linked SCID with a branch point mutation due to substitution of T for A 15 bp 5{prime} of the start of IL2RG exon 3. This mutation resulted in undetectable IL2RG mRNA by Northern blot. Linkage analysis and sequencing of IL2RG DNA in this family proved the mutation to have originated in the germline of the proband`s grandfather, an immunocompetent individual who contributed an X chromosome with normal IL2RG to one daughter and a mutated X to the another.

  18. Positron Emission Tomographic Imaging of Iodine 124 Anti–Prostate Stem Cell Antigen–Engineered Antibody Fragments in LAPC-9 Tumor–Bearing Severe Combined Immunodeficiency Mice

    Directory of Open Access Journals (Sweden)

    Jeffrey V. Leyton

    2013-05-01

    Full Text Available The humanized antibody (hu1G8 has been shown to localize to prostate stem cell antigen (PSCA and image PSCA-positive xenografts. We previously constructed hu1G8 anti-PSCA antibody fragments and tested them for tumor targeting and the ability to image prostate cancer at early and late time points postinjection by positron emission tomography (PET. We now then compare the PET imaging and the radioactivity accumulation properties in prostate cancer tumors and nontarget tissues to determine the superior 124I-labeled hu1G8 antibody format. 124I-labeled diabody, minibody, scFv-Fc, scFv-Fc double mutant (DM, and parental IgG were administered into severe combined immunodeficiency (SCID mice bearing LAPC-9 xenografts and followed by whole-body PET imaging of mice at preselected time points. Regions of interest were manually drawn around tumor and nontarget tissues and evaluated for radioactivity accumulation. The 124I-hu1G8 IgG has its best time point for tumor high-contrast imaging at 168 hours postinjection. The 124I-hu1G8 minibody at 44 hours postinjection results in superior tumor high-contrast imaging compared to the other antibody formats. The 124I-hu1G8 minibody at 44 hours postinjection also has comparable percent tumor radioactivity compared to 124I-hu1G8 IgG at 168 hours postinjection. The 124I-hu1G8 minibody is the best engineered hu1G8 antibody format for imaging prostate cancer.

  19. Generation of recombination activating gene-1-deficient neonatal piglets: a model of T and B cell deficient severe combined immune deficiency.

    Directory of Open Access Journals (Sweden)

    Tetsuya Ito

    Full Text Available Although severe combined immune deficiency (SCID is a very important research model for mice and SCID mice are widely used, there are only few reports describing the SCID pig models. Therefore, additional research in this area is needed. In this study, we describe the generation of Recombination activating gene-1 (Rag-1-deficient neonatal piglets in Duroc breed using somatic cell nuclear transfer (SCNT with gene targeting and analysis using fluorescence-activated cell sorting (FACS and histology. We constructed porcine Rag-1 gene targeting vectors for the Exon 2 region and obtained heterozygous/homozygous Rag-1 knockout cell colonies using SCNT. We generated two Rag-1-deficient neonatal piglets and compared them with wild-type neonatal piglets. FACS analysis showed that Rag-1 disruption causes a lack of Immunoglobulin M-positive B cells and CD3-positive T cells in peripheral blood mononuclear cells. Consistent with FACS analysis, histological analysis revealed structural defects and an absence of mature lymphocytes in the spleen, mesenteric lymph node (MLNs, and thymus in Rag-1-deficient piglets. These results confirm that Rag-1 is necessary for the generation of lymphocytes in pigs, and Rag-1-deficient piglets exhibit a T and B cell deficient SCID (T-B-SCID phenotype similar to that of rodents and humans. The T-B-SCID pigs with Rag-1 deficiency generated in this study could be a suitably versatile model for laboratory, translational, and biomedical research, including the development of a humanized model and assessment of pluripotent stem cells.

  20. [Clinical study on application of intermittent hemofiltration combined with hemoperfusion in the early stage of severe burn in the prevention and treatment of sepsis].

    Science.gov (United States)

    Guo, Wanli; Lei, Jin; Duan, Peng; Ma, Xiaoming

    2015-08-01

    To investigate the effects of application of intermittent hemofiltration combined with hemoperfusion (HP) in the early stage of severe burn in the prevention and treatment of sepsis. Forty severely burned patients, admitted to our burn ward from June 2011 to March 2013, conforming to the study criteria, were divided into conventional treatment group (CT, n=20) and blood purification group (BP, n=20) according to the random number table. Patients in group CT received CT according to the accepted principles of treatment for a severe burn. Patients in group BP received CT and intermittent hemofiltration combined with HP once respectively on post injury day (PID) 3, 5, and 7, spanning 6 to 8 hours for each treatment. On PID 3, 5, 7, 10, and 14, body temperature, heart rate, and respiratory rate were recorded; white blood cell count (WBC), neutrophil granulocytes, blood urea nitrogen (BUN), and creatinine were determined; levels of IL-1, IL-6, TNF-α, and high-mobility group box 1 (HMGB1) in serum were determined by ELISA; level of LPS in serum was determined with the chromogenic substrate limulus amebocyte lysate method; level of procalcitonin (PCT) in serum was determined by double antibody sandwich immune chemiluminescence method. The symptoms and signs of sepsis were observed during the treatment. Data were processed with Fisher's exact test, chi-square test, analysis of variance for repeated measurement, and LSD-t test. (1) Except for that on PID 5, the mean body temperature of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.87 to 2.97, P values below 0.05). The heart rate was significantly slower in patients of group BP than in group CT from PID 3 to 14 (with t values from 1.78 to 3.59, P values below 0.05). Except for that on PID 3, the respiratory rate of patients in group BP was significantly slower than that of group CT at each of the rest time points (with t values from 1.93 to 2.85, P

  1. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  2. Parallelization of Reversible Ripple-carry Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock

    2009-01-01

    {O}(m\\cdot k)$. The underlying mechanisms of the parallelization scheme are formally proven correct. We also show designs for garbage-less reversible comparison circuits. We compare the circuit costs of the resulting ripple-block carry adder with known optimized reversible ripple-carry adders in measures...... wherein $m$ parallel $k$-bit reversible ripple-carry adders are combined to form a reversible $mk$-bit \\emph{ripple-block carry adder} with logic depth $\\mathcal{O}(m+k)$ for a \\emph{minimal} logic depth $\\mathcal{O}(\\sqrt{mk})$, thus improving on the $mk$-bit ripple-carry adder logic depth $\\mathcal...

  3. Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Anderson Dik Wai Luk

    2017-07-01

    Full Text Available BackgroundSevere combined immunodeficiency (SCID is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH has been associated with earlier diagnosis.ObjectiveThe aim of this study was to identify the clinical features that affect age at diagnosis (AD and time to the diagnosis of SCID.MethodsFrom 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP, and AD were selected for study.ResultsA total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57. A total of 29 patients had a positive FH. Candidiasis (n = 27 and bacillus Calmette–Guérin (BCG vaccine infection (n = 19 were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002 and diagnosis by 2 months (p = 0.008, but not shorter time to diagnosis (p = 0.494. Candidiasis was associated with later AD by 2 months (p = 0.008 and longer time to diagnosis by 0.55 months (p = 0.003. BCG infections were not associated with age or time to diagnosis.ConclusionFH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of

  4. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  5. Cost-effectiveness analysis of three different combinations of inhalers for severe and very severe chronic obstructive pulmonary disease patients at a tertiary care teaching hospital of South India

    Directory of Open Access Journals (Sweden)

    Mohammed Altaf

    2015-01-01

    Rs. 661/- per SFD. Conclusion: This study highlights the favorable therapeutic performance of combined inhaled bronchodilators and corticosteroids (SF/FB/FF, thus suggesting that healthcare costs would be also affected positively. Results from our study showed that SF and FB were the most effective strategies in the treatment of COPD, with a slight clinical superiority of SF. The FF strategy was not much effective (i.e. associated with fewer outcomes and higher costs.

  6. Reverse logistics - a framework

    OpenAIRE

    Brito, Marisa; Dekker, Rommert

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of products, processes and actors. In addition we provide a decision framework for Reverse Logistics and we present it according to long, medium and short term decisions, i.e. strategic-tactic-operational decis...

  7. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of

  8. [The differences in the estimation of depression severity by psychiatrists and patients during the combined treatment with agomelatine (a multicenter study "EMOTSIA")].

    Science.gov (United States)

    Medvedev, V E; Retiunsky, K Yu; Ovchinnikov, A A; Barylnik, Yu B; Shmilovich, A A; Antokhin, E Yu; Usov, G M; Cheremin, R A; Poletsky, V M; Onegin, A V; Kireeva, I P; Frolova, V I; Filippova, N V; Antonova, A A; Deeva, M A; Onegina, D A

    2016-01-01

    To compare the prognosis of depression severity estimated by the physician and by the patient based on the treatment outcome. One hundred and seven patients with depression were examined. Mental status was assessed with HАМ-D, SHAPS, CGI-S, CGI-I, PGI-S, PGI-I and VAS. A data analysis was performed. There were differences in the estimation of depression severity by psychiatrists and patients. Moreover, the scores on HАМ-D and CGI-S were not consistent when assessed by psychiatrists. As the severity of depression decreased and patient's state improved during the treatment with agomelatine (valdoxan), the assessments of the changes by the psychiatrist and the patient became similar. Agomelatine (valdoxan) is effective and tolerable in the treatment of depression of any severity. The differences between the psychiatrist's and patient's estimation of the depression severity at baseline using different psychometric scales can level the prognostic value of treatment outcome.

  9. Combination effect of sponge iron and calcium nitrate on severely eutrophic urban landscape water: an integrated study from laboratory to fields.

    Science.gov (United States)

    Wang, Guan-Bai; Wang, Yi; Zhang, Ying

    2018-01-06

    In this study, the in situ restoration of urban landscape water through the combined application of sponge iron (SI) and calcium nitrate (CN) was conducted in the Xi'an Moat of China. The combination effect of SI and CN on the phosphorus (P) control was explored through laboratory and field experiments. Results showed that the optimum mass ratio of SI and CN was 4:1, and the optimum dosage of combined SI and CN was 1.4 g/L for controlling eutrophication in the water body at Xi'an Moat. The field experiment demonstrated that SI and CN efficiently controlled P concentration in overlying and interstitial water and obtained a maximum efficiency of 88.6 and 65.2% in soluble reactive P locking, respectively. The total P, organic P, and Ca-bound P contents in sediment simultaneously increased by 7.7, 15.2, and 2.4%, respectively, after 56 days. Therefore, the combined application of SI and CN achieved the goal of transferring the P from overlying and interstitial water to the sediment. Considering the environmental effect and economic investment, the combined application of SI and CN at a mass ratio of 4:1 and dosage of 1.4 g/L is an excellent choice for the in situ rehabilitation of eutrophic water with a high internal P load.

  10. ‘Picking People to Hate’: Reversible reversals in stand-up comedy

    DEFF Research Database (Denmark)

    Keisalo, Marianna Päivikki

    2017-01-01

    Generally speaking, ritual reversals mean switching to the opposite of what is considered ‘the normal order’. Such reversals can occur, for example, in terms of social hierarchies in rites of passage, in action in carnival, or in the framing of action as ritual or performance. For comedic figures...... such as clowns and tricksters, reversals are part of their semiotic technique. By ‘reversible reversals’ I refer to the characteristic ambiguity of comedic performance and the ability of comedic figures to play with, combine, or shift between opposite traits, actions, and perspectives. In this sense, comedy can...... be said to constitute a series of reversals. Jokes can also be reversible in the way their outcomes are indeterminate: they may have a number of interpretations and effects but none are guaranteed. To illustrate this, I will demonstrate how reversals figure in organizing jokes and performance in a bit...

  11. Multidrug evolutionary strategies to reverse antibiotic resistance

    Science.gov (United States)

    Baym, Michael; Stone, Laura K.; Kishony, Roy

    2017-01-01

    Antibiotic treatment has two conflicting effects: the desired, immediate effect of inhibiting bacterial growth and the undesired, long-term effect of promoting the evolution of resistance. Although these contrasting outcomes seem inextricably linked, recent work has revealed several ways by which antibiotics can be combined to inhibit bacterial growth while, counterintuitively, selecting against resistant mutants. Decoupling treatment efficacy from the risk of resistance can be achieved by exploiting specific interactions between drugs, and the ways in which resistance mutations to a given drug can modulate these interactions or increase the sensitivity of the bacteria to other compounds. Although their practical application requires much further development and validation, and relies on advances in genomic diagnostics, these discoveries suggest novel paradigms that may restrict or even reverse the evolution of resistance. PMID:26722002

  12. Reversible posterior leukoencephalopathy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang Joon [Chungnam National Univ. School of Medicine, Cheonju (Korea, Republic of); Song, Soon-Young; Koo, Ja Hong [Kwandong Univ. College of Medicine, Myungji Hospital, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine Pochon CHA Univ., Seoul (Korea, Republic of)

    2001-10-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  13. Global analysis of gene expression in maize leaves treated with low temperature. II. Combined effect of severe cold (8 °C) and circadian rhythm.

    Science.gov (United States)

    Jończyk, M; Sobkowiak, A; Trzcinska-Danielewicz, J; Skoneczny, M; Solecka, D; Fronk, J; Sowiński, P

    2017-10-01

    In maize seedlings, severe cold results in dysregulation of circadian pattern of gene expression causing profound modulation of transcription of genes related to photosynthesis and other key biological processes. Plants live highly cyclic life and their response to environmental stresses must allow for underlying biological rhythms. To study the interplay of a stress and a rhythmic cue we investigated transcriptomic response of maize seedlings to low temperature in the context of diurnal gene expression. Severe cold stress had pronounced effect on the circadian rhythm of a substantial proportion of genes. Their response was strikingly dual, comprising either flattening (partial or complete) of the diel amplitude or delay of expression maximum/minimum by several hours. Genes encoding central oscillator components behaved in the same dual manner, unlike their Arabidopsis counterparts reported earlier to cease cycling altogether upon cold treatment. Also numerous genes lacking circadian rhythm responded to the cold by undergoing up- or down-regulation. Notably, the transcriptome changes preceded major physiological manifestations of cold stress. In silico analysis of metabolic processes likely affected by observed gene expression changes indicated major down-regulation of photosynthesis, profound and multifarious modulation of plant hormone levels, and of chromatin structure, transcription, and translation. A role of trehalose and stachyose in cold stress signaling was also suggested. Meta-analysis of published transcriptomic data allowed discrimination between general stress response of maize and that unique to severe cold. Several cis- and trans-factors likely involved in the latter were predicted, albeit none of them seemed to have a major role. These results underscore a key role of modulation of diel gene expression in maize response to severe cold and the unique character of the cold-response of the maize circadian clock.

  14. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa

    DEFF Research Database (Denmark)

    Hartel, Bas P.; Lofgren, Maria; Huygen, Patrick L. M.

    2016-01-01

    Objectives Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates...... the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. Design...... A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA...

  15. Relationship Between Serum DNA Replication, Clinicopathological Characteristics and Prognosis of Hepatitis B Virus-associated Glomerulonephritis with Severe Proteinuria by Lamivudine Plus Adefovir Dipivoxil Combination Therapy.

    Science.gov (United States)

    Jiang, Wei; Liu, Tuo; Dong, Hui; Xu, Yan; Liu, Li Qiu; Guan, Guang Ju; Liu, Xiang Chun

    2015-03-01

    To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. Several findings were demonstrated with the increase of serum HBV DNA: 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly (P%lt;0.05), while the plasma level of albumin decreased significantly (P%lt;0.05); The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group (P%lt;0.01). With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  16. The association of self-regulation with weight loss maintenance after an intensive combined lifestyle intervention for children and adolescents with severe obesity

    NARCIS (Netherlands)

    Halberstadt, Jutka; de Vet, Emely; Nederkoorn, Chantal; Jansen, Anita; van Weelden, Ottelien H; Eekhout, Iris; Heymans, Martijn W.; Seidell, Jacob C.

    2017-01-01

    BACKGROUND: Knowledge is limited on the role the ability to self-regulate plays in the long-term outcome of obesity treatment in children and adolescents with severe obesity. The purpose of this study was to determine whether the ability to self-regulate after an one year intensive, partly

  17. Rapid and Sensitive Detection of Norovirus Genomes in Oysters by a Two-Step Isothermal Amplification Assay System Combining Nucleic Acid Sequence-Based Amplification and Reverse Transcription-Loop-Mediated Isothermal Amplification Assays▿

    Science.gov (United States)

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-01-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h. PMID:18456857

  18. Rapid and Sensitive Detection of Norovirus Genomes in Oysters by a Two-Step Isothermal Amplification Assay System Combining Nucleic Acid Sequence-Based Amplification and Reverse Transcription-Loop-Mediated Isothermal Amplification Assays▿

    OpenAIRE

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-01-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h.

  19. Rapid and sensitive detection of norovirus genomes in oysters by a two-step isothermal amplification assay system combining nucleic acid sequence-based amplification and reverse transcription-loop-mediated isothermal amplification assays.

    Science.gov (United States)

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-06-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h.

  20. Efficacy and tolerability of triple-combination therapy with olmesartan, amlodipine, and hydrochlorothiazide: a subgroup analysis of patients stratified by hypertension severity, age, sex, and obesity.

    Science.gov (United States)

    Kreutz, Reinhold; Ammentorp, Bettina; Laeis, Petra; de la Sierra, Alejandro

    2014-10-01

    This prespecified subgroup analysis of a phase III study examined the effect of adding hydrochlorothiazide (HCTZ) to olmesartan (OLM)/amlodipine (AML) in patients with moderate to severe hypertension stratified by age, sex, body mass index, and hypertension severity. A total of 2690 patients, aged 18 years and older, with seated blood pressure (SeBP) ≥160/100 mm Hg received placebo or OLM/AML 20/5 mg, 40/5 mg, or 40/10 mg during a 2-week, double-blind, run-in period, after which they were allocated to one of eight treatment groups with the same OLM/AML dose or with HCTZ 12.5 mg or 25 mg added for 8 weeks. By week 10, greater reductions in SeBP were observed in each OLM/AML/HCTZ group (Page, sex, and obesity. ©2014 Wiley Periodicals, Inc.

  1. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

  2. REAL TEXTILE WASTEWATER RECLAMATION USING A COMBINED COAGULATION/ FLOCCULATION/ MEMBRANE FILTRATION SYSTEM AND THE EVALUATION OF SEVERAL NATURAL MATERIALS AS FLOCCULANT AIDS

    OpenAIRE

    Köse, Tijen Ennil; Çalışkan Biroğul, Nilüfer

    2016-01-01

    ABSTRACTA coagulation/flocculation/membrane filtration process was applied to two real textile wastewaters in Turkey. Aluminum sulfate and ferric sulfate were used as coagulants and several natural materials, namely limestone, magnesite, kaoline, pumice, and sedipür (polyelectrolyte), were used as flocculant aids. The effects of pH, coagulant dosage, and the type and dosage of flocculant aids on the color and chemical oxygen demand (COD) of wastewater were studied. The experimental results sh...

  3. Uterine hypertonia and nuchal cord causing severe fetal bradycardia in a parturient receiving combined spinal-epidural analgesia during labor: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Uma Srivastava

    2012-01-01

    Full Text Available Fetal bradycardia is common following spinal opioids administered for pain relief during labor. This slowing is usually benign and short lived. Although it leads to some anxiety among obstetricians and anesthesiologists, it rarely results in urgent operative delivery. Here, we are reporting a case where urgent caesarean delivery was needed due to severe and persistent fetal bradycardia following low-dose intrathecal fentanyl. Fetal bradycardia possibly was due to hypertonic uterine contractions complicated by tightly wrapped cord round the neck.

  4. Severe loin pain following renal biopsy in a high-risk patient: A case report of a rare combination of pseudoaneurysm and arterio-venous fistula

    Directory of Open Access Journals (Sweden)

    Desai Madhav

    2011-01-01

    Full Text Available We report a 50-year-old male patient with diabetes mellitus and hypertension who presented with low-grade fever, anuria and renal failure. He had no prior history of nephropathy and retinopathy. Since anuria persisted, a renal biopsy was performed using automated gun, under ultrasound guidance. Two hours after the renal biopsy was performed, the patient developed severe left loin pain that required analgesics and sedatives. Ultrasound of the abdomen performed immediately, two hours and four hours after the biopsy, did not reveal any hematoma. The hemoglobin was stable when the patient developed loin pain, but after eight hours decreased to 9.1 g/dL, and computed tomography scan of the abdomen revealed a big peri-nephric hematoma around the left kidney. He was managed with blood transfusions and a selective angiogram was done. It revealed a pseudoaneurysm and arterio-venous fistula from the segmental artery of lower pole of the left kidney; both were closed by using microcoils and liquid embolic agent N-butyl-cyanoacrylate (NBCA. The only risk factor the patient had at the time of renal biopsy was severe renal failure. Our case suggests that severe loin pain immediately after renal biopsy in a patient with renal failure warrants careful follow-up of hemoglobin and imaging, even if initial imaging is normal. Further fall of hemoglobin necessitates early evaluation with angiogram, which helps in diagnosing the treatable, although rare, complications like pseudoaneurysm and arterio-venous fistula.

  5. Assessing Major Accident Risks to Support Land-Use Planning Using a Severity-Vulnerability Combination Method: A Case Study in Dagushan Peninsula, China.

    Science.gov (United States)

    Ma, Shuming; Zhang, Shushen; Yu, Chen; Zheng, Hongbo; Song, Guobao; Semakula, Henry Musoke; Chai, Yingying

    2015-08-01

    Major accident risks posed by chemical hazards have raised major social concerns in today's China. Land-use planning has been adopted by many countries as one of the essential elements for accident prevention. This article aims at proposing a method to assess major accident risks to support land-use planning in the vicinity of chemical installations. This method is based on the definition of risk by the Accidental Risk Assessment Methodology for IndustrieS (ARAMIS) project and it is an expansion application of severity and vulnerability assessment tools. The severity and vulnerability indexes from the ARAMIS methodology are employed to assess both the severity and vulnerability levels, respectively. A risk matrix is devised to support risk ranking and compatibility checking. The method consists of four main steps and is presented in geographical information-system-based maps. As an illustration, the proposed method is applied in Dagushan Peninsula, China. The case study indicated that the method could not only aid risk regulations on existing land-use planning, but also support future land-use planning by offering alternatives or influencing the plans at the development stage, and thus further enhance the roles and influence of land-use planning in the accident prevention activities in China. © 2015 Society for Risk Analysis.

  6. Combination of icotinib, surgery, and internal-radiotherapy of a patient with lung cancer severely metastasized to the vertebrae bones with EGFR mutation: a case report

    Directory of Open Access Journals (Sweden)

    Qu LL

    2015-06-01

    Full Text Available Li-Li Qu, Hai-Feng Qin, Hong-Jun Gao, Xiao-Qing Liu Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Science, Beijing, People’s Republic of China Abstract: A 48-year-old Chinese female was referred to us regarding EGFR-mutated advanced non-small cell lung cancer, and metastasis to left scapula and vertebrae bones which caused pathological fracture at T8 and T10 thoracic vertebrae. An aggressive combined therapy with icotinib, vertebrae operation, and radioactive particle implantation and immunotherapy was proposed to prevent paraplegia, relieve pain, and control the overall and local tumor lesions. No postoperative symptoms were seen after surgery, and the pain was significantly relieved. Icotinib merited a 31-month partial response with grade 1 diarrhea as its drug-related adverse event. High dose of icotinib was administered after pelvis lesion progression for 3 months with good tolerance. Combination therapy of icotinib, surgery, and internal radiation for metastases of the vertebrae bones from non-small cell lung cancer seems to be a very promising technique both for sufficient pain relief and for local control of the tumor, vertebrae operation can be an encouraging option for patients with EFGR positive mutation and good prognosis indicator. Keywords: lung cancer, spinal metastasis, pathological fracture, spinal canal stenosis, icotinib

  7. Reverse Core Engine with Thrust Reverser

    Science.gov (United States)

    Suciu, Gabriel L. (Inventor); Chandler, Jesse M. (Inventor)

    2017-01-01

    An engine system has a gas generator, a bi-fi wall surrounding at least a portion of the gas generator, a casing surrounding a fan, and the casing having first and second thrust reverser doors which in a deployed position abut each other and the bi-fi wall.

  8. Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain.

    Science.gov (United States)

    Wallace, Mark S; Kosek, Peter S; Staats, Peter; Fisher, Robert; Schultz, David M; Leong, Michael

    2008-04-01

    To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose. Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase. Outpatient clinics. Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20 mg/day). Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60 microg/day and was titrated to a maximum of 7.2 microg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion. Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (> or = 15% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5% (95% confidence interval: -9.4% to 38.5%) from baseline to week 5 and varied during the extension phase (range: -0.4% to 42.8%). Mean percentage change from baseline in systemic opioid consumption was -14.3% at week 5 and varied considerably during the extension phase. Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.

  9. Open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of morphine in patients receiving ziconotide for severe chronic pain.

    Science.gov (United States)

    Webster, Lynn R; Fakata, Keri L; Charapata, Steven; Fisher, Robert; MineHart, Michael

    2008-04-01

    To assess the safety and efficacy of adding intrathecal morphine to intrathecal ziconotide in patients treated with stable ziconotide doses. Multicenter, open-label study with a 4-week morphine titration phase during which ziconotide was held constant and an extension phase during which dosing of either drug could vary. Outpatient clinics. Patients with suboptimal pain relief receiving stable ziconotide doses (> or = 4.8 microg/day) in one of two ongoing ziconotide trials. Ziconotide dosing remained constant during the titration phase; intrathecal morphine titration was based on each patient's daily systemic opioid dose at the study's start. During the extension phase, intrathecal ziconotide and morphine dosing were adjusted per investigator discretion. Safety was assessed primarily via adverse events. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. Twenty-five patients enrolled. The most common (> or = 10% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) treatment-emergent adverse events included dizziness, peripheral edema, pruritus, and nausea. From the initial visit to week 4, visual analog scale of pain intensity scores improved by a mean of 26.3% (95% confidence interval: 15.6%-37.1%) but varied during the extension phase (mean percentage change from the initial visit ranged from -0.4% at week 16 to -35.0% at week 72). Mean percentage decrease in systemic opioid consumption from the initial visit was 49.1% at week 4 and 51.2% at week 56 of the extension phase. Intrathecal morphine, combined with stable intrathecal ziconotide doses, reduced pain in patients with previously suboptimal pain relief on ziconotide monotherapy.

  10. Novel Designs of Quantum Reversible Counters

    Science.gov (United States)

    Qi, Xuemei; Zhu, Haihong; Chen, Fulong; Zhu, Junru; Zhang, Ziyang

    2016-11-01

    Reversible logic, as an interesting and important issue, has been widely used in designing combinational and sequential circuits for low-power and high-speed computation. Though a significant number of works have been done on reversible combinational logic, the realization of reversible sequential circuit is still at premature stage. Reversible counter is not only an important part of the sequential circuit but also an essential part of the quantum circuit system. In this paper, we designed two kinds of novel reversible counters. In order to construct counter, the innovative reversible T Flip-flop Gate (TFG), T Flip-flop block (T_FF) and JK flip-flop block (JK_FF) are proposed. Based on the above blocks and some existing reversible gates, the 4-bit binary-coded decimal (BCD) counter and controlled Up/Down synchronous counter are designed. With the help of Verilog hardware description language (Verilog HDL), these counters above have been modeled and confirmed. According to the simulation results, our circuits' logic structures are validated. Compared to the existing ones in terms of quantum cost (QC), delay (DL) and garbage outputs (GBO), it can be concluded that our designs perform better than the others. There is no doubt that they can be used as a kind of important storage components to be applied in future low-power computing systems.

  11. Islet xenograft destruction in the hu-PBL-severe combined immunodeficient (SCID) mouse necessitates anti-CD3 preactivation of human immune cells

    Science.gov (United States)

    Gysemans, C; Waer, M; Laureys, J; Depovere, J; Pipeleers, D; Bouillon, R; Mathieu, C

    2000-01-01

    Introduction of the hu-PBL-SCID mouse model has yielded a potentially useful tool for research in transplantation. The aim of this study was to define the conditions necessary for a reconstituted human immune system to destroy in a consistent manner rat islet xenografts in the alloxan-diabetic hu-PBL-SCID mouse. We examined different time points of hu-PBL reconstitution, different transplantation sites of the islets and several hu-PBL reconstitution protocols. Major differences in graft destruction were observed between the different hu-PBL reconstitution protocols, irrespective of timing of hu-PBL reconstitution or site of transplantation. Although preactivation of hu-PBL did not improve the level of hu-PBL chimerism, histological and immunohistochemical analysis of the grafts revealed a severe human lymphocytic infiltration and β cell destruction only in the grafts of mice receiving preactivated hu-PBL. This β cell injury resulted in impaired glucose tolerance, with in some animals recurrence of hyperglycaemia, and decreased insulin and C-peptide levels after glucose stimulation. Therefore, we conclude that activation of hu-PBL prior to transfer is essential in achieving xenograft infiltration and destruction in hu-PBL-SCID mice. The need for immune manipulation suggests that interactions between hu-PBL and xenografts in this model may be hampered by incompatibilities in cross-species adhesion and/or activation signals. PMID:10971525

  12. Superthin Abdominal Wall Glove-Like Flap Combined With Vacuum-Assisted Closure Therapy for Soft Tissue Reconstruction in Severely Burned Hands or With Infection.

    Science.gov (United States)

    Wang, Fei; Liu, Sheng; Qiu, Le; Ma, Ben; Wang, Jian; Wang, Yong-Jie; Peszel, April; Chen, Xu-Lin

    2015-12-01

    Severe burn and infection to hands always involves the deep structures, such as tendons, joints, and bones. These wounds cannot be closed immediately and therefore creates a high risk for complication. We presented 9 cases with deep dermal burns to the dorsal of the hand (6 electrical burns and 3 thermal crush injuries) with wound infections in 2 cases. The vacuum-assisted closure system was used continuously until the flap reconstruction was performed. A random pattern and superthin abdominal wall skin flap-like glove was designed. The flap was transferred to the defected portion of the dorsum of the hand and resected from the abdominal wall about 3 weeks later. The flaps in 8 of the patients treated by this technique survived completely and partial necrosis of the distal flap occurred in 1 patient. The defect resolved after operative treatment and the function of the hands and fingers were successfully salvaged. All patients resulted in having a satisfactory aesthetic outcome with no or minor discomfort at the abdominal donor area. Integration of the vacuum-assisted closure system and the superthin abdominal wall glove-like flap reconstruction appeared to be successful and should be considered in patients with severely burned hands.

  13. Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)

    DEFF Research Database (Denmark)

    Bregenholt, S; Claesson, Mogens Helweg

    1998-01-01

    Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall-transpla......Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall......-transplanted scid mice with IBD. Increased fractions of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-2-positive CD4+ T cells were found in the spleens of diseased mice compared with control mice. Moreover, a small but significant population of CD4+ T cells which stained positive...... for granulocyte-macrophage colony-stimulating factor (GM-CSF) was found in scid mice with IBD but was virtually absent in congenic non-scid control mice. Cloning of granulocyte/ macrophage colony-forming cells (G/M-CFC) revealed that both non-transplanted scid mice and scid mice with IBD had an 8-14-fold increase...

  14. Multiple reversal olfactory learning in honeybees

    Directory of Open Access Journals (Sweden)

    Theo Mota

    2010-07-01

    Full Text Available In multiple reversal learning, animals trained to discriminate a reinforced from a non-reinforced stimulus are subjected to various, successive reversals of stimulus contingencies (e.g. A+ vs. B-, A- vs. B+, A+ vs. B-. This protocol is useful to determine whether or not animals learn to learn and solve successive discriminations faster (or with fewer errors with increasing reversal experience. Here we used the olfactory conditioning of proboscis extension reflex to study how honeybees Apis mellifera perform in a multiple reversal task. Our experiment contemplated four consecutive differential conditioning phases involving the same odors (A+ vs. B- to A- vs. B+ to A+ vs. B- to A- vs. B+. We show that bees in which the weight of reinforced or non-reinforced stimuli was similar mastered the multiple olfactory reversals. Bees which failed the task exhibited asymmetric responses to reinforced and non-reinforced stimuli, thus being unable to rapidly reverse stimulus contingencies. Efficient reversers did not improve their successive discriminations but rather tended to generalize their choice to both odors at the end of conditioning. As a consequence, both discrimination and reversal efficiency decreasedalong experimental phases. This result invalidates a learning-to-learn effect and indicates that bees do not only respond to the actual stimulus contingencies but rather combine these with an average of past experiences with the same stimuli.  

  15. Brain-computer interface training combined with transcranial direct current stimulation in patients with chronic severe hemiparesis: Proof of concept study.

    Science.gov (United States)

    Kasashima-Shindo, Yuko; Fujiwara, Toshiyuki; Ushiba, Junichi; Matsushika, Yayoi; Kamatani, Daiki; Oto, Misa; Ono, Takashi; Nishimoto, Atsuko; Shindo, Keiichiro; Kawakami, Michiyuki; Tsuji, Tetsuya; Liu, Meigen

    2015-04-01

    Brain-computer interface technology has been applied to stroke patients to improve their motor function. Event-related desynchronization during motor imagery, which is used as a brain-computer interface trigger, is sometimes difficult to detect in stroke patients. Anodal transcranial direct current stimulation (tDCS) is known to increase event-related desynchronization. This study investigated the adjunctive effect of anodal tDCS for brain-computer interface training in patients with severe hemiparesis. Eighteen patients with chronic stroke. A non-randomized controlled study. Subjects were divided between a brain-computer interface group and a tDCS- brain-computer interface group and participated in a 10-day brain-computer interface training. Event-related desynchronization was detected in the affected hemisphere during motor imagery of the affected fingers. The tDCS-brain-computer interface group received anodal tDCS before brain-computer interface training. Event-related desynchronization was evaluated before and after the intervention. The Fugl-Meyer Assessment upper extremity motor score (FM-U) was assessed before, immediately after, and 3 months after, the intervention. Event-related desynchronization was significantly increased in the tDCS- brain-computer interface group. The FM-U was significantly increased in both groups. The FM-U improvement was maintained at 3 months in the tDCS-brain-computer interface group. Anodal tDCS can be a conditioning tool for brain-computer interface training in patients with severe hemiparetic stroke.

  16. Fumaric acid esters in combination with a 6-week course of narrow-band UVB provides for an accelerated response as compared to fumaric acid esters monotherapy in patients with moderate to severe plaque psoriasis: A randomized prospective clinical study.

    Science.gov (United States)

    Tzaneva, S; Geroldinger, A; Trattner, H; Tanew, A

    2017-11-08

    Fumaric acid esters are (FAE) safe and effective in patients with moderate to severe psoriasis but have a slow onset of action. A short-term combination with narrow-band UVB (NB UVB) may substantially accelerate the therapeutic response in the induction phase of treatment. To assess the synergistic effect of a 6-week course of NB UVB phototherapy in addition to fumaric acid esters in adult patients with moderate to severe plaque psoriasis. In this randomized, assessor-blinded trial patients with a Psoriasis Area and Severity Index (PASI) of ≥10 and a body surface area (BSA) of ≥10 were randomized to either monotherapy with FAE (n=16) or a combination of FAE with NB UVB (n=14). The primary outcome parameter of the study was the mean PASI reduction after 6 weeks of treatment. In addition, the PASI 75 response, the psoriasis log-based area and severity index (PLASI) and the dermatology life quality index (DLQI) were assessed as secondary outcome measures. Thirty patients (19 males, 11 females; median age 52 years, IQR 36;56) were analysed. The mean reduction in PASI after 6 weeks was significantly greater with the combination treatment as compared to FAE monotherapy (p=0.016). This was paralleled by a much faster improvement in DLQI in the combination group than in the FAE monotherapy group. Adding a 6-week course of narrow-band UVB to FAE both accelerates and augments the therapeutic response during the early phase of treatment and increases quality of life in patients with moderate-to-severe plaque psoriasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Transient increase of fractional anisotropy in reversible vasogenic edema

    OpenAIRE

    Kimura-Ohba, Shihoko; Yang, Yi; Thompson, Jeffrey; Kimura, Tomonori; Salayandia, Victor M; Cosse, Melissa; Yang, Yirong; Sillerud, Laurel O.; Rosenberg, Gary A.

    2016-01-01

    Brain vasogenic edema, involving disruption of the blood-brain barrier, is a common pathological condition in several neurological diseases, with a heterogeneous prognosis. It is sometimes reversible, as in posterior reversible encephalopathy syndrome, but often irreversible and our current clinical tools are insufficient to reveal its reversibility. Here, we show that increased fractional anisotropy in magnetic resonance imaging is associated with the reversibility of vasogenic edema. Sponta...

  18. Severe Obesity Confounds the Interpretation of Low-Dose Dexamethasone Test Combined with the Administration of Ovine Corticotrophin-Releasing Hormone in Childhood Cushing Syndrome

    Science.gov (United States)

    Batista, Dalia L.; Courcoutsakis, Nikos; Riar, Jehan; Keil, Margaret F.; Stratakis, Constantine A.

    2008-01-01

    Context: Suppression of cortisol secretion with a low-dose dexamethasone (Dex) followed by the administration of ovine CRH (Dex-oCRH) is used in the evaluation of adults with a pseudo-Cushing syndrome state (PCSS) vs. Cushing syndrome (CS). Objective: The aim of the study was to determine the value of Dex-oCRH testing in the investigation of childhood CS. Design: We conducted a retrospective analysis of data from children evaluated for CS vs. PCSS from 1998–2006; body mass index Z (BMIZ) and height-for-age Z (HAZ) scores were estimated. Setting: A clinical research center was the setting for the study. Main Outcome Measures: The main outcomes were confirmation of the diagnosis of CS by histology and response to Dex-oCRH. Results: Thirty-two children (ages 3–17 yr) were studied: 11 had CS and 21 had PCSS; of the latter, 11 had a BMIZ score greater than 2. Children with CS had a mean HAZ score of −1.3 ± 0.51 vs. 0.31 ± 0.38 in nonobese and 0.71 ± 0.39 in obese children (P < 0.001). The previously established criterion of a cortisol of 1.4 μg/dl (38 nmol/liter) after Dex-oCRH identified all 10 normal children who were not very obese and those with CS; 5 of 11 normal children with more severe obesity had cortisol values greater than 1.4 μg/dl (38 nmol/liter) after Dex-oCRH, lowering the test specificity to 55%. Without consideration for obesity, an increase of the cutoff cortisol value after Dex-oCRH to 3.2 μg/dl (88 nmol/liter) will have 91% sensitivity and 95% specificity; the corresponding values for a cutoff of 2.2 μg/dl (61 nmol/liter) were 100 and 90.5%, respectively. Conclusion: Our study showed that height gain is a simple way of distinguishing children with PCCS from those with CS; the interpretation of Dex-oCRH in children is confounded by severe obesity, which limits the utility of this test. PMID:18728165

  19. Applying Data Mining to Classify Age by Intestinal Microbiota in 92 Healthy Men Using a Combination of Several Restriction Enzymes for T-RFLP Experiments.

    Science.gov (United States)

    Kobayashi, Toshio; Osaki, Takako; Oikawa, Shinya

    2014-01-01

    The composition of the intestinal microbiota was measured following consumption of identical meals for 3 days in 92 Japanese men, and terminal restriction fragment length polymorphism (T-RFLP) was used to analyze their feces. The obtained operational taxonomic units (OTUs) and the subjects' ages were classified by using Data mining (DM) software that compared these data with continuous data and for 5 partitions for age divided at 5 years intervals between the ages of 30 and 50. The DM provided Decision trees in which the selected OTUs were closely related to the ages of the subjects. DM was also used to compare the OTUs from the T-RFLP data with seven restriction enzymes (two enzymes of 516f-BslI and 516f-HaeIII, two enzymes of 27f-MspI and 27f-AluI, three enzymes of 35f-HhaI, 35f-MspI and 35f-AluI) and their various combinations. The OTUs delivered from the five enzyme-digested partitions were analyzed to classify their age clusters. For use in future DM processing, we discussed the enzymes that were effective for accurate classification. We selected two OTUs (HA624 and HA995) that were useful for classifying the subject's ages. Depending on the 16S rRNA sequences of the OTUs, Ruminicoccus obeum clones 1-4 were present in 18 of 36 bacterial candidates in the older age group-related OTU (HA624). On the other hand, Ruminicoccus obeum clones 1-33 were present in 65 of 269 candidates in the younger age group-related OUT (HA995).

  20. Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Amidfar, M; Khiabany, M; Kohi, A; Salardini, E; Arbabi, M; Roohi Azizi, M; Zarrindast, M-R; Mohammadinejad, P; Zeinoddini, A; Akhondzadeh, S

    2017-02-01

    Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl-d-aspartate receptor antagonist, in humans. Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P = 0·018 and P depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing. © 2016 John Wiley & Sons Ltd.

  1. A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.

    Science.gov (United States)

    Kaeppler, Ulrich; Stiefl, Nikolaus; Schiller, Markus; Vicik, Radim; Breuning, Alexander; Schmitz, Werner; Rupprecht, Daniel; Schmuck, Carsten; Baumann, Knut; Ziebuhr, John; Schirmeister, Tanja

    2005-11-03

    The coronavirus main protease, M(pro), is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M(pro) inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed M(pro) inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a K(i) value of 35.3 muM. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.

  2. Community-based trial results of combination clindamycin 1%--benzoyl peroxide 5% topical gel plus tretinoin microsphere gel 0.04% or 0.1% or adapalene gel 0.1% in the treatment of moderate to severe acne.

    Science.gov (United States)

    Kircik, Leon

    2007-07-01

    Acne is characterized by different types of lesions at different stages of development. Therefore, combination therapy may offer numerous advantages, including enhanced efficacy and better tolerability. The addition of benzoyl peroxide (BPO) to all long-term antibiotic treatment is widely advocated to help suppress the emergence of antibiotic-resistant bacteria. Topical retinoids are recommended as early initiation treatment of most patients with acne because they target most mechanisms of acne pathogenesis. In the clinical setting, therapeutic regimens that include retinoids and topical antibiotic-BPO combination formulations frequently are prescribed. This study investigated the efficacy and safety of combination therapy with clindamycin 1%-BPO 5% topical gel plus tretinoin microsphere (RAM) gel 0.04% or 0.1% or adapalene (AP) gel 0.1% in moderate to severe acne.

  3. Development of a robust reverse tone pattern transfer process

    Science.gov (United States)

    Khusnatdinov, Niyaz; Doyle, Gary; Resnick, Douglas J.; Ye, Zhengmao; LaBrake, Dwayne; Milligan, Brennan; Alokozai, Fred; Chen, Jerry

    2017-03-01

    Pattern transfer is critical to any lithographic technology, and plays a significant role in defining the critical features in a device layer. As both the memory and logic roadmaps continue to advance, greater importance is placed on the scheme used to do the etching. For many critical layers, a need has developed which requires a multilayer stack to be defined in order to perform the pattern transfer. There are many cases however, where this standard approach does not provide the best results in terms of critical dimension (CD) fidelity and CD uniformity. As an example, when defining a contact pattern, it may be advantageous to apply a bright field mask (in order to maximize the normalized inverse log slope (NILS)) over the more conventional dark field mask. The result of applying the bright field mask in combination with positive imaging resist is to define an array of pillar patterns, which then must be converted back to holes before etching the underlying dielectric material. There have been several publications on tone reversal that is introduced in the resist process itself, but often an etch transfer process is applied to reverse the pattern tone. The purpose of this paper is to describe the use of a three layer reverse tone process (RTP) that is capable of reversing the tone of every printed feature type. The process utilizes a resist pattern, a hardmask layer and an additional protection layer. The three layer approach overcomes issues encountered when using a single masking layer. Successful tone reversal was demonstrated both on 300mm wafers and imprint masks, including the largest features in the pattern, with dimensions as great as 60 microns. Initial in-field CD uniformity is promising. CDs shifted by about 2.6nm and no change was observed in either LER or LWR. Follow-up work is required to statistically qualify in-field CDU and also understand both across wafer uniformity and feature linearity.

  4. Case Report: Whole exome sequencing identifies variation c.2308G>A p.E770K in RAG1 associated with B- T- NK+ severe combined immunodeficiency [version 2; referees: 2 approved, 1 not approved

    Directory of Open Access Journals (Sweden)

    Geeta Madathil Govindaraj

    2017-10-01

    Full Text Available Severe combined immunodeficiency is a large clinically heterogeneous group of disorders caused by a defect in the development of humoral or cellular immune responses. At least 13 genes are known to be involved in the pathophysiology of the disease and the mutation spectrum in SCID has been well documented. Mutations of the recombination-activating genes RAG 1 and RAG 2 are associated with a range of clinical presentations including, severe combined immunodeficiency and autoimmunity. Recently, our understanding of the molecular basis of immune dysfunction in RAG deficiency has improved tremendously with newer insights into the ultrastructure of the RAG complex. In this report, we describe the application of whole exome sequencing for arriving at a molecular diagnosis in a child suffering from B- T- NK+ severe combined immunodeficiency. Apart from making the accurate molecular diagnosis, we also add a genetic variation c.2308G>A p.E770K to the compendium of variations associated with the disease.

  5. An algebra of reversible computation.

    Science.gov (United States)

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  6. Rotating Reverse-Osmosis for Water Purification

    Science.gov (United States)

    Lueptow, RIchard M.

    2004-01-01

    A new design for a water-filtering device combines rotating filtration with reverse osmosis to create a rotating reverse- osmosis system. Rotating filtration has been used for separating plasma from whole blood, while reverse osmosis has been used in purification of water and in some chemical processes. Reverse- osmosis membranes are vulnerable to concentration polarization a type of fouling in which the chemicals meant not to pass through the reverse-osmosis membranes accumulate very near the surfaces of the membranes. The combination of rotating filtration and reverse osmosis is intended to prevent concentration polarization and thereby increase the desired flux of filtered water while decreasing the likelihood of passage of undesired chemical species through the filter. Devices based on this concept could be useful in a variety of commercial applications, including purification and desalination of drinking water, purification of pharmaceutical process water, treatment of household and industrial wastewater, and treatment of industrial process water. A rotating filter consists of a cylindrical porous microfilter rotating within a stationary concentric cylindrical outer shell (see figure). The aqueous suspension enters one end of the annulus between the inner and outer cylinders. Filtrate passes through the rotating cylindrical microfilter and is removed via a hollow shaft. The concentrated suspension is removed at the end of the annulus opposite the end where the suspension entered.

  7. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow o...... justification for low-level machine code for reversible microprocessors as well as high-level block-structured reversible languages. We give examples for both such languages and illustrate them with a lossless encoder for permutations given by Dijkstra....

  8. Tubal Ligation Reversal

    Science.gov (United States)

    ... and other factors. Success rates may be as high as 80 percent or as low as near 40 percent depending on your circumstances. Tubal ligation reversal is abdominal surgery, which carries a risk of infection, bleeding and ...

  9. Sex reversal in vertebrates

    OpenAIRE

    2016-01-01

    This special topic issue of Sexual Development gives an overview of sex reversal in vertebrates, from fishes naturally changing their sex, to rodents escaping the mammalian SRY-determining system. It offers eight up-to-date reviews on specific subjects in sex reversal, considering fishes, amphibians, reptiles, birds, marsupials, and placental mammals, including humans. The broad scope of represented animals makes this ideal for students and researchers, especially those interested in the...

  10. PROCESSING REVERSE LOGISTICS INVENTORIES

    OpenAIRE

    Bajor, Ivona; Novačko, Luka; Ogrizović, Dario

    2014-01-01

    Developed logistics systems have organized reverse logistics flows and are continuously analyzing product returns, tending to detect patterns in oscillations of returning products in certain time periods. Inventory management in reverse logistics systems depends on different criteria, regarding goods categories, formed contracts between subjects of supply chains, uncertainty in manufacturer’s quantities of DOA (dead on arrival) products, etc. The developing logistics systems, such as the Croa...

  11. Time reversibility, computer simulation, algorithms, chaos

    CERN Document Server

    Hoover, William Graham

    2012-01-01

    A small army of physicists, chemists, mathematicians, and engineers has joined forces to attack a classic problem, the "reversibility paradox", with modern tools. This book describes their work from the perspective of computer simulation, emphasizing the author's approach to the problem of understanding the compatibility, and even inevitability, of the irreversible second law of thermodynamics with an underlying time-reversible mechanics. Computer simulation has made it possible to probe reversibility from a variety of directions and "chaos theory" or "nonlinear dynamics" has supplied a useful vocabulary and a set of concepts, which allow a fuller explanation of irreversibility than that available to Boltzmann or to Green, Kubo and Onsager. Clear illustration of concepts is emphasized throughout, and reinforced with a glossary of technical terms from the specialized fields which have been combined here to focus on a common theme. The book begins with a discussion, contrasting the idealized reversibility of ba...

  12. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus

    2007-01-01

    Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families......, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb...... the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation....

  13. Design of Annulated Pyrazoles As Inhibitors of HIV-1 Reverse Transcriptase

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Z.K.; Harris, S.F.; Arora, N.; Javanbakht, H.; Li, Y.; Fretland, J.; Davidson, J.P.; Billedeau, J.R.; Gleason, S.; Hirschfeld, D.; Kennedy-Smith, J.J.; Mirzadegan, T.; Roetz, R.; Smith, M.; Sperry, S.; Suh, J.M.; Wu, J.; Tsing, S.; Villasenor, A.G.; Paul, A.; Su, G.

    2009-05-26

    Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of HIV. These regimens are extremely effective in suppressing virus replication. Structure-based optimization of diaryl ether inhibitors led to the discovery of a new series of pyrazolo[3,4-c]pyridazine NNRTIs that bind the reverse transcriptase enzyme of human immunodeficiency virus-1 (HIV-RT) in an expanded volume relative to most other inhibitors in this class. The binding mode maintains the {beta}13 and {beta}14 strands bearing Pro236 in a position similar to that in the unliganded reverse transcriptase structure, and the distribution of interactions creates the opportunity for substantial resilience to single point mutations. Several pyrazolopyridazine NNRTIs were found to be highly effective against wild-type and NNRTI-resistant viral strains in cell culture.

  14. Nonlocal Transport in the Reversed Field Pinch

    Energy Technology Data Exchange (ETDEWEB)

    Spizzo, G.; White, R. B.; Cappello, S.; Marrelli, L.

    2009-09-21

    Several heuristic models for nonlocal transport in plasmas have been developed, but they have had a limited possibility of detailed comparision with experimental data. Nonlocal aspects introduced by the existence of a known spectrum of relatively stable saturated tearing modes in a low current reversed field pinch offers a unique possibility for such a study. A numerical modelling of the magnetic structure and associated particle transport is carried out for the reversed-field pinch experiment at the Consorzio RFX, Padova, Italy. A reproduction of the tearing mode spectrum with a guiding center code1 reliably reproduces the observed soft X-ray tomography. Following particle trajectories in the stochastic magnetic field shows the transport across the unperturbed flux surfaces to be due to a spectrum of Levy flights, with the details of the spectrum position dependent. The resulting transport is subdiffusive, and cannot be described by Rechester-Rosenbluth diffusion, which depends on a random phase approximation. If one attempts to fit the local transport phenomenologically, the subdiffusion can be fit with a combination of diffusion and inward pinch2. It is found that whereas passing particles explore the stochastic field and hence participate in Levy flights, the trapped particles experience normal neoclassical diffusion. A two fluid nonlocal Montroll equation is used to model this transport, with a Levy flight defined as the motion of an ion during the period that the pitch has one sign. The necessary input to the Montroll equation consists of a time distribution for the Levy flights, given by the pitch angle scattering operator, and a distribution of the flight distances, determined numerically using a guiding center code. Results are compared to experiment. The relation of this formulation to fractional kinetics is also described.

  15. Subsidiary Roles and Reverse Knowledge Transfer

    DEFF Research Database (Denmark)

    Rabbiosi, Larissa

    2011-01-01

    coordination mechanisms and knowledge flows from the subsidiary to the parent company, known as reverse knowledge transfer. It is crucial to understand the interdependencies between subsidiary roles and key coordination mechanisms, such as subsidiary autonomy, personal and electronic-based coordination...... mechanisms. This paper, therefore, offers new insights into the impact of coordination mechanisms on reverse knowledge transfer. On the basis of a data set consisting of 280 dyads between foreign subsidiaries and their parent companies, two distinctive configurations are found to positively affect the extent...... of reverse knowledge transfer. The first is the combination of a high degree of subsidiary autonomy and greater use of personal coordination mechanisms, and the second is the combination of low subsidiary autonomy and greater use of electronic-based coordination mechanisms. However, the relevance...

  16. Reversible Communicating Processes

    Directory of Open Access Journals (Sweden)

    Geoffrey Brown

    2016-02-01

    Full Text Available Reversible distributed programs have the ability to abort unproductive computation paths and backtrack, while unwinding communication that occurred in the aborted paths. While it is natural to assume that reversibility implies full state recovery (as with traditional roll-back recovery protocols, an interesting alternative is to separate backtracking from local state recovery. For example, such a model could be used to create complex transactions out of nested compensable transactions where a programmer-supplied compensation defines the work required to "unwind" a transaction. Reversible distributed computing has received considerable theoretical attention, but little reduction to practice; the few published implementations of languages supporting reversibility depend upon a high degree of central control. The objective of this paper is to demonstrate that a practical reversible distributed language can be efficiently implemented in a fully distributed manner. We discuss such a language, supporting CSP-style synchronous communication, embedded in Scala. While this language provided the motivation for the work described in this paper, our focus is upon the distributed implementation. In particular, we demonstrate that a "high-level" semantic model can be implemented using a simple point-to-point protocol.

  17. Reversible arithmetic logic unit for quantum arithmetic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert; Axelsen, Holger Bock

    2010-01-01

    and logical operations in one unit. Combined with a suitable control unit, the ALU permits the construction of an r-Turing complete computing device. The garbage-free ALU developed in this communication requires only 6n elementary reversible gates for five basic arithmetic-logical operations on two n...

  18. Complex polarity reversals in a geodynamo model

    Science.gov (United States)

    Olson, Peter L.; Glatzmaier, Gary A.; Coe, Robert S.

    2011-04-01

    Complex polarity reversals in numerical dynamos driven by thermo-chemical convection are analyzed in terms of magnetic field intensity variations, transitional field structure, and other observable characteristics. Our most Earth-like dynamos are characterized by long stable polarity chrons with dipole-dominant magnetic fields punctuated by occasional polarity reversals, and are found within a transition region of parameter space between non-reversing strongly dipolar dynamos and chaotic multi-polar-type dynamos. Dynamos in the transition region have elevated dipole terms, reduced quadrupole terms, magnetic energy that decreases slowly with spherical harmonic degree, and broadband dipole frequency spectra. Their axial dipole intensity histograms are trimodal, with large modes representing the stable polarity states and an intermediate mode representing the transitional multi-polar state. The dipole family intensity exceeds the quadrupole family intensity on the core-mantle boundary during stable polarity times, but during transitions the two families are similar. A complex dynamo model reversal is compared with paleomagnetic reconstructions around the Matuyama-Brunhes polarity transition. Both start with a gradual decrease of the dipole intensity, followed by a precursor reversal and transient polarity recovery, then a rapid dipole collapse and a final reversal that initiates with reverse flux generation in one hemisphere. Virtual geomagnetic poles (VGPs) from sites near the reverse flux trace complex paths and cross the equator several thousand years before the simpler VGP paths from more distant sites, and magnetic intensity variations during the dynamo model reversal correlate with intensity variations inferred for the Matuyama-Brunhes transition.

  19. A phase IV, open-label study evaluating the use of triple-combination therapy with minocycline HCl extended-release tablets, a topical antibiotic/retinoid preparation and benzoyl peroxide in patients with moderate to severe acne vulgaris.

    Science.gov (United States)

    Zaenglein, Andrea L; Shamban, Ava; Webster, Guy; Del Rosso, James; Dover, Jeffrey S; Swinyer, Leonard; Stein, Linda; Lin, Xiaoming; Draelos, Zoe; Gold, Michael; Thiboutot, Diane

    2013-06-01

    Moderate to severe acne vulgaris is often treated with a combination of an oral antibiotic, topical antibiotic/retinoid, and benzoyl peroxide (BP), but data are limited on the efficacy of this and other combination regimens that incorporate both oral and topical therapies. Patients were required to be aged 12-30 years with moderate to severe acne (grades 3-4 acne on the Investigator's Global Assessment [IGA]) and deemed potential candidates for treatment with isotretinoin. Enrolled patients were given triple-combination therapy, defined in this study as oral minocycline HCl extended release 1 mg/kg QD, 6% BP foaming cloths used QD, and clindamycin phosphate 1.2%/tretinoin 0.025% gel applied QD, and were evaluated at baseline and weeks 2, 4, 8, and 12. A total of 97 patients were enrolled in the study. At week 12, 89% of patients had at least a one-grade improvement from baseline IGA and 96% had at least a one-grade improvement from baseline Global Aesthetic Improvement Scale score. Mean ± SD in- flammatory, non-inflammatory, and total lesion counts decreased from baseline by 61.8% ± 38.3%, 48.8% ± 34.5%, and 56.5% ± 29.9%, respectively. The percentage of patients evaluated as candidates for isotretinoin by independent photographic review was 77% (69/90) at baseline and only 16% (14/90) at week 12. Treatment-related adverse events (AEs) occurred in eight of 97 (8%) patients. Triplecombination therapy was not associated with any serious AEs or AEs leading to discontinuation. Triple-combination therapy was well tolerated and substantially reduced facial acne lesion counts, with 84% of patients judged to no longer be candidates for isotretinoin therapy by study end. These data support the clinical observation that a triple-combination regimen incorporating oral minocycline (dosed by patient weight), BP foaming cloths 6% QD, and clindamycin phosphate 1.2%/ tretinoin 0.025% gel QD can substantially improve moderate to severe acne vulgaris.

  20. Reversed extension flow

    DEFF Research Database (Denmark)

    Nielsen, Jens Kromann; Rasmussen, Henrik K.

    2008-01-01

    Afilament stretching rheometer (FSR) was used for measuring the start-up of uni-axial elongational flow followed by reversed bi-axial flow, both with a constant elongational rate. A narrow molecular mass distribution linear polystyrene with a molecular weight of 145 kg / mole wis subjected...... to the start-up of elongation for three Hencky strain units and subsequently the reversed flow. The integral molecular stress function formulation within the 'interchain pressure' concept agrees with the experiments. In the experiments the Hencky strain at which the str~ss becomes zero (the recovery strain...

  1. Clinical laboratory evaluation of a reverse CAMP test for presumptive identification of Clostridium perfringens.

    OpenAIRE

    Buchanan, A G

    1982-01-01

    Ninety-six percent of Clostridium perfringens isolates from clinical specimens were reverse CAMP test positive, whereas several other Clostridium species tested were reverse CAMP test negative. C. perfringens was detected by direct inoculation of clinical specimens to reverse CAMP plates, and the reverse CAMP procedure provided reliable presumptive identification of this organism.

  2. Determination of adenosine deaminase activity in dried blood spots by a nonradiochemical assay using reversed-phase high-performance liquid chromatography

    NARCIS (Netherlands)

    van Kuilenburg, A. B. P.; Zoetekouw, L.; Meijer, J.; Kuijpers, T. W.

    2010-01-01

    Adenosine deaminase (ADA) deficiency is a rare metabolic disease causing severe combined immunodeficiency (SCID). An assay to determine ADA activity in dried blood spots was developed using reversed-phase HPLC. The assay was linear with reaction times up to at least 4 hours, and protein

  3. Reversing Discrimination: A Perspective

    Science.gov (United States)

    Pati, Gopal; Reilly, Charles W.

    1977-01-01

    Examines the debate over affirmative action and reverse discrimination, and discusses how and why the present dilemma has developed. Suggests that organizations can best address the problem through an honest, in-depth analysis of their organizational structure and management practices. (JG)

  4. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  5. REVERSE SUPPLY CHAIN

    Directory of Open Access Journals (Sweden)

    Tomasz DOMAGAŁA

    2013-10-01

    Full Text Available The paper focuses on the presentation of the reverse supply chain, of which the role in the modern business grows along with the increasing number of environmental regulations and possibilities of reducing an operating cost. The paper also describes main problems in developing the profitable chain and possibilities to take an action in order to overcome them.

  6. Sex Reversal in Birds.

    Science.gov (United States)

    Major, Andrew T; Smith, Craig A

    2016-01-01

    Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

  7. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  8. Posterior Reversible Leukoencephalopathy Syndrome Associated with Pazopanib

    Directory of Open Access Journals (Sweden)

    Robert Foerster

    2013-04-01

    Full Text Available A 62-year-old female patient with metastatic renal cell carcinoma under third-line treatment with pazopanib for 8 weeks suddenly developed severe headaches, grand mal seizures and paresis of the left arm in combination with gait instability as well as nausea and vomiting during her vacation abroad. The emergency physician measured systolic blood pressure values over 300 mm Hg and suspected a stroke. The CT imaging without contrast agent in a local hospital did not show any pathologic findings despite bone metastases. The colleagues suspected cerebral metastases or meningeosis carcinomatosa and referred the patient to our department for further diagnostics and treatment planning. An MRI scan ruled out the suspected cerebral metastases or meningeosis carcinomatosa, but showed signs of reversible posterior leukoencephalopathy syndrome (RPLS in the form of band-like hyperintensities as a sign of cytotoxic edema in the gray and white matter of the left parietal lobe. The patient then reported that similar blood pressure values had been measured shortly after the start of a first-line therapy with sunitinib, so that we discontinued the current treatment with pazopanib. Within 6 days the neurologic symptoms vanished and the patient was discharged. An intermittent hypertension persisted. A follow-up MRI 3 weeks later showed an RPLS-typical cortical infarction in the affected area. RPLS should be considered as the actual reason for neurologic findings in hypertensive patients with known metastatic cancers under tyrosine kinase inhibitor therapy.

  9. Intervention Studies of Inhaled Corticosteroids Combined with Long-acting Theophylline or Long-acting β2-agonists in Patients with Moderate to Severe Asthma: A Randomized, Controlled Study.

    Science.gov (United States)

    Wang, Yan; Chen, Ping; Dai, Anna; Shang, Shengyun; Kong, Lingfei

    2016-12-01

    To evaluate and contrast the therapeutic effect and safety of fluticasone aerosol combined with theophylline tablets in patients with moderate to severe asthma, compared with salmeterol/fluticasone propionate aerosol. After a screening period, patients meeting the inclusion criteria were randomly assigned to the experiment group (fluticasone aerosol combined with theophylline tablets) or the control group (salmeterol/fluticasone aerosol combined with placebo tablets) for 12 weeks of treatment. The main outcome measurements were forced expiratory volume in 1 second and fractional concentration of exhaled nitric oxide value, whereas the secondary measures were forced vital capacity, peak expiratory flow value, and Asthma Control Test/Asthma Quality of Life Questionnaire score. Forty-four cases completed the course, with 23 cases in the experiment group and 21 cases in the control group. The forced expiratory volume in 1 second values of both groups were significantly improved from before (P theophylline tablets is worth considering for use in primary hospitals or for low-income populations. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  10. Airway remodeling and its reversibility in equine asthma

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Lavoie

    2017-06-01

    Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

  11. Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray

    Science.gov (United States)

    Bayer, D K; Martinez, C A; Sorte, H S; Forbes, L R; Demmler-Harrison, G J; Hanson, I C; Pearson, N M; Noroski, L M; Zaki, S R; Bellini, W J; Leduc, M S; Yang, Y; Eng, C M; Patel, A; Rodningen, O K; Muzny, D M; Gibbs, R A; Campbell, I M; Shaw, C A; Baker, M W; Zhang, V; Lupski, J R; Orange, J S; Seeborg, F O; Stray-Pedersen, A

    2014-01-01

    In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8+ T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20–30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5–10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients. PMID:25046553

  12. Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

    Science.gov (United States)

    Wen, Shameng; Meng, Qingkun; Feng, Chao; Tang, Chaojing

    2017-01-01

    Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

  13. Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

    Directory of Open Access Journals (Sweden)

    Shameng Wen

    Full Text Available Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

  14. Simultaneous detection and differentiation of dengue virus serotypes 1-4, Japanese encephalitis virus, and West Nile virus by a combined reverse-transcription loop-mediated isothermal amplification assay

    Directory of Open Access Journals (Sweden)

    Yin Jianhua

    2011-07-01

    Full Text Available Abstract Background Rapid identification and differentiation of mosquito-transmitted flaviviruses in acute-phase sera of patients and field-caught vector mosquitoes are important for the prediction and prevention of large-scale epidemics. Results We developed a flexible reverse-transcription loop-mediated isothermal amplification (RT-LAMP unit for the detection and differentiation of dengue virus serotypes 1-4 (DENV1-4, Japanese encephalitis virus (JEV, and West Nile virus (WNV. The unit efficiently amplified the viral genomes specifically at wide ranges of viral template concentrations, and exhibited similar amplification curves as monitored by a real-time PCR engine. The detection limits of the RT-LAMP unit were 100-fold higher than that of RT-PCR in 5 of the six flaviviruses. The results on specificity indicated that the six viruses in the assay had no cross-reactions with each other. By examining 66 viral strains of DENV1-4 and JEV, the unit identified the viruses with 100% accuracy and did not cross-react with influenza viruses and hantaviruses. By screening a panel of specimens containing sera of 168 patients and 279 pools of field-caught blood sucked mosquitoes, results showed that this unit is high feasible in clinical settings and epidemiologic field, and it obtained results 100% correlated with real-time RT-PCR. Conclusions The RT-LAMP unit developed in this study is able to quickly detect and accurately differentiate the six kinds of flaviviruses, which makes it extremely feasible for screening these viruses in acute-phase sera of the patients and in vector mosquitoes without the need of high-precision instruments.

  15. Returnable containers: an example of reverse logistics

    NARCIS (Netherlands)

    L.G. Kroon (Leo); G.M.C. Vrijens

    1996-01-01

    textabstractConsiders the application of returnable containers as an example of reverse logistics. A returnable container is a type of secondary packaging that can be used several times in the same form, in contrast with traditional cardboard boxes. For this equipment to be used, a system for the

  16. Long-acting reversible hormonal contraception

    African Journals Online (AJOL)

    progestogen injections, are less severe and are reversed shortly after the implant is removed.15 The most common side effects are irregular bleeding, headaches, weight gain, acne, .... decrease in sex drive. Changes in menstrual bleeding are common, including lighter bleeding, irregular bleeding, infrequent bleeding and.

  17. An Open Visualization Toolkit for Reverse Architecting

    NARCIS (Netherlands)

    Telea, Alexandru; Maccari, Alessandro; Riva, Claudio

    2002-01-01

    Maintenance and evolution of complex software systems (such as large telecom embedded devices) involve activities such as reverse engineering (RE) and software visualization. Although several RE tools exist, we found their architecture hard to adapt to the domain specific requirements posed by our

  18. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 3.75% for the once-daily treatment of moderate to severe acne vulgaris.

    Science.gov (United States)

    Pariser, David M; Rich, Phoebe; Cook-Bolden, Fran E; Korotzer, Andrew

    2014-09-01

    To evaluate efficacy, safety, and tolerability of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 3.75% (clindamycin-BP 3.75%) aqueous gel in moderate to severe acne vulgaris. A total of 498 patients, 12-40 years of age, were randomized to receive clindamycin-BP 3.75% or vehicle in a double-blind, controlled 12-week, 2-arm study evaluating safety and efficacy using inflammatory and noninflammatory lesion counts, Evaluator Global Severity Scores (EGSS) and subject self-assessment (SSA). In addition, patients completed a patient satisfaction survey (PSS), acne-specific QoL questionnaire, and assessed their facial skin for shininess/oiliness. Clindamycin-BP 3.75% demonstrated statistical superiority to vehicle in reducing both inflammatory and noninflammatory lesions and acne severity. Clindamycin-BP 3.75% showed greater efficacy relative to vehicle in assessments of skin oiliness, SSA and PSS. No substantive differences were seen in cutaneous tolerability among treatment groups and no patients discontinued treatment with Clindamycin-BP 3.75% because of adverse events. Data from controlled studies may differ from clinical practice. It is not possible to determine the contributions from the individual active ingredients. Clindamycin-BP 3.75% provides statistically significant greater efficacy than vehicle with a favorable safety and tolerability profile.

  19. Describing and optimizing reversible logic using a functional language

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal

    2012-01-01

    This paper presents the design of a language for the description and optimisation of reversible logic circuits. The language is a combinator-style functional language designed to be close to the reversible logical gate-level. The combinators include high-level constructs such as ripples, but also...... the description of arbitrary sized circuits. The combination of the functional language and the restricted reversible model results in many arithmetic laws, which provide more possibilities for term rewriting and, thus, the opportunity for good optimisation....... the recognisable inversion combinator f^(-1), which defines the inverse function of f using an efficient semantics. It is important to ensure that all circuits descriptions are reversible, and furthermore we must require this to be done statically. This is en- sured by the type system, which also allows...

  20. Improving Passive Time Reversal Underwater Acoustic Communications Using Subarray Processing

    Directory of Open Access Journals (Sweden)

    Chengbing He

    2017-04-01

    Full Text Available Multichannel receivers are usually employed in high-rate underwater acoustic communication to achieve spatial diversity. In the context of multichannel underwater acoustic communications, passive time reversal (TR combined with a single-channel adaptive decision feedback equalizer (TR-DFE is a low-complexity solution to achieve both spatial and temporal focusing. In this paper, we present a novel receiver structure to combine passive time reversal with a low-order multichannel adaptive decision feedback equalizer (TR-MC-DFE to improve the performance of the conventional TR-DFE. First, the proposed method divides the whole received array into several subarrays. Second, we conduct passive time reversal processing in each subarray. Third, the multiple subarray outputs are equalized with a low-order multichannel DFE. We also investigated different channel estimation methods, including least squares (LS, orthogonal matching pursuit (OMP, and improved proportionate normalized least mean squares (IPNLMS. The bit error rate (BER and output signal-to-noise ratio (SNR performances of the receiver algorithms are evaluated using simulation and real data collected in a lake experiment. The source-receiver range is 7.4 km, and the data rate with quadrature phase shift keying (QPSK signal is 8 kbits/s. The uncoded BER of the single input multiple output (SIMO systems varies between 1 × 10 − 1 and 2 × 10 − 2 for the conventional TR-DFE, and between 1 × 10 − 2 and 1 × 10 − 3 for the proposed TR-MC-DFE when eight hydrophones are utilized. Compared to conventional TR-DFE, the average output SNR of the experimental data is enhanced by 3 dB.

  1. Improving Passive Time Reversal Underwater Acoustic Communications Using Subarray Processing.

    Science.gov (United States)

    He, Chengbing; Jing, Lianyou; Xi, Rui; Li, Qinyuan; Zhang, Qunfei

    2017-04-24

    Multichannel receivers are usually employed in