The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

Energy Technology Data Exchange (ETDEWEB)

Rusch, V.W.; Griffin, B.R.; Livingston, R.B. (Univ. of Washington, Seattle (USA))

1989-10-01

Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

Role of care pathways in interprofessional teamwork.

Science.gov (United States)

Scaria, Minimol Kulakkottu

2016-08-24

Cohesive interprofessional teamwork is essential to successful healthcare services. Interprofessional teamwork is the means by which different healthcare professionals - with diverse knowledge, skills and talents - collaborate to achieve a common goal. Several interventions are available to improve teamwork in the healthcare setting. This article explores the role of care pathways in improving interprofessional teamwork. Care pathways enhance teamwork by promoting coordination, collaboration, communication and decision making to achieve optimal healthcare outcomes. They result in improved staff knowledge, communication, documentation and interprofessional relations. Care pathways also contribute to patient-centred care and increase patient satisfaction.

Prophylactic Role of Spermine in Rats Intoxicated With Lead and/or Gamma Irradiation

International Nuclear Information System (INIS)

Habieb, M.E.; Mohamed, M.A.; Hawas, A.M.; Abu-Khudir, R.; Mohamed, T.M.

2017-01-01

The current study was conducted to investigate the protective effect of spermine, a natural polyamine against toxicity of lead and /or gamma irradiation in male rats. Eight groups of rats were used in this study (control, irradiated group (6 GY), lead (40 mg/kg bw), spermine (10 mg/kg bw), lead plus irradiation, irradiation plus spermine, lead plus spermine, irradiation plus lead co-treated with spermine) for consecutive 14 days. Blood samples were used for complete blood count (CBC) and glucose 6-phosphate-dehydrogenase (G6PD) levels. Moreover, malondialdhyde (MDA), glutathione (GSH), metallothionein (MT) levels and catalase (CAT) activity were investigated in liver, kidney and brain. G6PD activity significantly decreased post exposure to lead and /or gamma irradiation. Hepatic, renal and brain MDA, GSH, MT and CAT were significantly increased in lead intoxicated group, while GSH, MT and CAT activity were significantly decreased in gamma-irradiated group. Spermine administration alleviated changes in CBC, G6PD, MDA, MT and CAT to normal control levels, but with significant increase in G6PD activity and platelets count. In conclusion, spermine acts as an antioxidant and plays a prophylactic role against intoxication with lead and/or gamma irradiation exposure.

Migraine - Prophylactic Treatment

Directory of Open Access Journals (Sweden)

Chowdhury Debashish

2002-01-01

Full Text Available Preventive therapy in migraine constitutes an important aspect of migraine management especially in patients who are not controlled or have significant disability despite taking drugs for acute management. In spite of te recent advances in understanding of the pathophysiology of migraine, the mechanisms of action of many preventive drugs are largely unknown. Further, these provide only about 50% reduction in frequency in about 2/3rds of migraine sufferers. Hence, risk-benefit ratio must be considered while prescribing these agents. Recent efforts to undertake large-scale meta-analysis to assess the efficacy of these agents have been rewarding and consensus guidelines have evolved. Propanolol, metoprolol, amitriptyline, sodium valproate, flunarizine and lisuride have emerged as first line drugs. The role of newer anti-convulsants and botox injections in refractory cases are being investigated. Availability, co-morbidities, medical contraindications, concomitant acute therapy and costs are important determinants for choosing a particular agent. This article reviews the guidelines to be followed in choosing the prophylactic treatment options for migraine.

Neutron activation appraisal of efficiency of herbs in prophylactic measures of teeth caries

International Nuclear Information System (INIS)

Zhumatov, U.Zh.

1997-01-01

The results of neutron activation analysis of elemental composition of teeth in experimental animals under conditions of pesticides and fluorine influence on an organism have been obtained and the role of black mulberry and zizyphus jujubi mill in prophylactics of teeth caries has been determined. (author). 5 refs., 1 tab

The Angelina Jolie Effect in Jewish Law: Prophylactic Mastectomy and Oophorectomy in BRCA Carriers

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Sharon Galper Grossman

2015-10-01

Full Text Available Background: Following the announcement of actress Angelina Jolie’s prophylactic bilateral mastectomies and subsequent prophylactic oophorectomy, there has been a dramatic increase in interest in BRCA testing and prophylactic surgery. Objective: To review current medical literature on the benefits of prophylactic mastectomy and oophorectomy among BRCA-positive women and its permissibility under Jewish law. Results: Recent literature suggests that in BRCA-positive women who undergo prophylactic oophorectomy the risk of dying of breast cancer is reduced by 90%, the risk of dying of ovarian cancer is reduced by 95%, and the risk of dying of any cause is reduced by 77%. The risk of breast cancer is further reduced by prophylactic mastectomy. Prophylactic oophorectomy and prophylactic mastectomy pose several challenges within Jewish law that call into question the permissibility of surgery, including mutilation of a healthy organ, termination of fertility, self-wounding, and castration. A growing number of Jewish legal scholars have found grounds to permit prophylactic surgery among BRCA carriers, with some even obligating prophylactic mastectomy and oophorectomy. Conclusion: Current data suggest a significant reduction in mortality from prophylactic mastectomy and oophorectomy in BRCA carriers. While mutilation of healthy organs is intrinsically forbidden in Jewish law, the ability to preserve human life may contravene and even mandate prophylactic surgery.

Cancer Registries and Monitoring the Impact of Prophylactic Human Papillomavirus Vaccines: The Potential Role

OpenAIRE

Saraiya, Mona; Goodman, Marc T.; Datta, S. Deblina; Chen, Vivien W.; Wingo, Phyllis A.

2008-01-01

The recent US Food and Drug Administration licensure of a prophylactic vaccine against oncogenic human papillomavirus (HPV) types 16 and 18, the first of its kind, poses unique challenges in postmarketing vaccine surveillance, especially in measuring vaccine effectiveness against biologic endpoints of HPV infection. Historically, the national system of population-based cancer registries in the US has provided high-quality data on cancer incidence and mortality for the most important biologic ...

Surgical site infection and timing of prophylactic antibiotics for appendectomy.

Science.gov (United States)

Wu, Wan-Ting; Tai, Feng-Chuan; Wang, Pa-Chun; Tsai, Ming-Lin

2014-12-01

Pre-operative prophylactic antibiotics may decrease the frequency of surgical site infection after appendectomy. However, the optimal timing for administration of pre-operative prophylactic antibiotics is unknown. The purpose of this study was to evaluate the effect of timing of prophylactic antibiotics on the frequency of surgical site infection after appendectomy. Medical records were reviewed retrospectively for 577 consecutive patients who had appendectomy for acute appendicitis from 2006 to 2009. Quality assurance guidelines for timing of prophylactic antibiotics before the skin incision were changed from 0 to 30 min before the skin incision (before June 2008) to 30 to 60 min before the skin incision (after June 2008). Surgical site infection occurred in 28 patients (4.9%). There was no difference in frequency of surgical site infection with different timing of pre-operative prophylactic antibiotic (pre-operative time 0 to 30 min: 9 infections [3.6%]; 31 to 60 min: 13 infections [5.4%]; 61 to 120 min: 5 infections [7.0%]; >120 min: 1 infection [6.6%]). Multivariable analysis showed that surgical site infection was associated significantly with medical comorbidity but not perforated appendicitis. The frequency of surgical site infection was independent of timing of preoperative prophylactic antibiotics but was associated with the presence of medical comorbidity.

Prophylactic antibiotics versus post- operative antibiotics in herniorraphy

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Abedulla Khan Kayamkani

2015-07-01

Full Text Available Postoperative surgical site infections are a major source of illness.  Infection results in longer hospital stay and higher costs.  Uses of preoperative antibiotics have been standardized and are being used routinely in most clinical surgeries and include controversial areas like breast surgery and herniorraphy. Objective of the study is to find out the benefit of prophylactic use of antibiotics in the management of herniorraphy.This project was carried out in a multispeciality tertiary care teaching hospital from 1st-30th April in 2002. Group 1 patients were treated prophylactically half an hour before surgery with single dose of I.V. antibiotics (injection.  Ampicillin 1gm + injection.  Gentamicin 80mg. Group 2 patients were treated post surgery with capsule. Ampicillin 500mg 4 times a day for 7 days and injection. Gentamicin twice a day for first 4 days. In case of group 1 patients only one out of 20 patients (5% was infected.  Whereas in-group 2 patients 5 out of 20 patients (25% were infected. The cost of prophylactic antibiotic treatment was Rs. 25.56 per patient.  The postoperative antibiotic treatment cost was Rs. 220.4 per patient.  That means postoperative treatment is around 8.62 times costlier than prophylactic treatment.             From this study it is evident that prophylactic (preoperative treatment is better than postoperative treatment with antibiotics.

Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.

Science.gov (United States)

Novikova, Natalia; Hofmeyr, G Justus; Essilfie-Appiah, George

2012-09-12

Amnioinfusion aims to relieve umbilical cord compression during labour by infusing a liquid into the uterine cavity. The objective of this review was to assess the effects of prophylactic amnioinfusion for women in labour with oligohydramnios, but not fetal heart deceleration, compared with therapeutic amnioinfusion only if fetal heart rate decelerations or thick meconium-staining of the liquor occur. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2012). Randomised trials comparing prophylactic amnioinfusion in women in labour with oligohydramnios but not fetal heart rate deceleration in labour with therapeutic amnioinfusion. The authors assessed trial quality and extracted data. One randomized trial of 116 women was included. No differences were found in the rate of caesarean section (risk ratio 1.29, 95% confidence interval 0.60 to 2.74). There were no differences in cord arterial pH, oxytocin augmentation, neonatal pneumonia or postpartum endometritis. Prophylactic amnioinfusion was associated with increased intrapartum fever (risk ratio 3.48, 95% confidence interval 1.21 to 10.05). There appears to be no advantage of prophylactic amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart rate decelerations or thick meconium-staining of the liquor occur.

Prophylactic and thermovision measurements of electric machines and equipment

Energy Technology Data Exchange (ETDEWEB)

Jedlicka, R; Brestovansky, L [Atomova Elektraren Bohunice, Jaslovske Bohunice (Slovakia)

1997-12-31

High-voltage measurements of generators, unit and service transformers and some significant motor drives used at a nuclear power plant are described in this paper. Thermovision measurements of electric machines and distribution systems are dealt with in the second part of the paper. Power electric equipment represent one of the most significant components of a nuclear power plant. Turbine mechanical energy is converted into the electrical energy within these equipment. Power generated by generators is transformed by transformers so that it can achieve appropriate parameters for both the transmission over the distribution system and the power plant service power supply. The service power supply switchboards and cables provide supply to motors and other consumers necessary for the nuclear power plant technological process. The whole complex of equipment has to be maintained in good technical conditions. It is necessary to make thermovision and prophylactic measurements to identify and verify the electric equipment technical condition. The mentioned measurements warn the operation staff in advance against both gradual deterioration of power connection contact resistances, i.e. power connections overheating, and the machine insulation systems condition deterioration. The operation staff try to prevent the electric equipment operation accidents by early removing the detected failures, thus, improving the nuclear safety. In order to provide the above-mentioned activities a special prophylactic measurement group was established at the NPP Bohunice in 1983. The group specialists make following types of measurements. 1. Prophylactic measurements of electric machines. Prophylactics of 220 MW generators and 6 MW service power generators; Prophylactics of both unit and service transformers and VHV bushings; Prophylactics of major 6 kV motor drives. 2. Thermovision measurements of current connections. (Abstract Truncated)

Prophylactic use of octreotide for asparaginase-induced acute pancreatitis.

Science.gov (United States)

Sakaguchi, Sachi; Higa, Takeshi; Suzuki, Mitsuyoshi; Fujimura, Junya; Shimizu, Toshiaki

2017-08-01

In the present study, we sought to evaluate the prophylactic use of octreotide for asparaginase-induced acute pancreatitis. We reviewed the medical records of seven patients in two institutions who received prophylactic octreotide for re-administration of asparaginase after asparaginase-induced acute pancreatitis. Three patients completed asparaginase treatment without developing pancreatitis, and four experienced recurrence of pancreatitis. A literature search using PubMed identified four additional patients in whom asparaginase was successfully re-administered with octreotide. Prophylactic use of octreotide may, thus, be warranted for patients who would benefit from re-administration of asparaginase for cancer treatment; however, careful observation is needed to monitor for breakthrough recurrence of pancreatitis.

The prophylactic effect of valproate on glyceryltrinitrate induced migraine

DEFF Research Database (Denmark)

Tvedskov, Jesper Filtenborg; Thomsen, L L; Iversen, H K

2004-01-01

In this study the human glyceryltrinitrate (GTN) model of migraine was for the first time used to test the effect of a prophylactic drug. We chose to test valproate due to its well documented effect as a migraine prophylactic drug. Efficacy of this compound would support the usefulness of the mod...

Prophylactic Interventions in Neonatology: How Do They Fare in Real Life?

Science.gov (United States)

Rolnitsky, Asaph; Lee, Shoo K; Piedbouf, Bruno; Harrison, Adele; Shah, Prakesh S

2015-10-01

This study aims to evaluate the association of prophylactic antenatal steroids, indomethacin, and phototherapy with extremely preterm infant outcomes in a pragmatic setting. Retrospective study of infants born at <28 weeks gestation and admitted to 26 Canadian Neonatal Network neonatal intensive care units between 2010 and 2012. Mortality, severe neurological injury, retinopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, nosocomial infection, and patent ductus arteriosus ligation rates were compared between infants who received antenatal steroids, prophylactic indomethacin, and/or prophylactic phototherapy and those who did not. Of 3,465 eligible infants, 2,900 (84%) received antenatal steroids, 269 (8%) prophylactic indomethacin, and 403 (12%) prophylactic phototherapy. Associations were observed between antenatal steroids and mortality (adjusted odds ration [aOR] 0.47 [0.33-0.66]) and severe neurological injury (aOR 0.60 [0.46-0.77]), indomethacin and ductus arteriosus ligations (aOR 0.52 [0.31-0.87]), but not severe neurological injury (aOR 1.12 [0.81-1.54]), but phototherapy was not associated with any of the neonatal outcomes despite reductions in bilirubin. Antenatal steroids were associated with reduced mortality and neurological injury, prophylactic indomethacin was not associated with reduction in neurological injury and phototherapy was not associated with any improvement in neonatal outcomes. In a pragmatic setting, outside randomized controlled trials, the effectiveness and safety of prophylactic interventions in extremely preterm neonates vary; ongoing monitoring is warranted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Role of healthcare workers in early epidemic spread of Ebola: policy implications of prophylactic compared to reactive vaccination policy in outbreak prevention and control.

Science.gov (United States)

Coltart, Cordelia E M; Johnson, Anne M; Whitty, Christopher J M

2015-10-19

Ebola causes severe illness in humans and has epidemic potential. How to deploy vaccines most effectively is a central policy question since different strategies have implications for ideal vaccine profile. More than one vaccine may be needed. A vaccine optimised for prophylactic vaccination in high-risk areas but when the virus is not actively circulating should be safe, well tolerated, and provide long-lasting protection; a two- or three-dose strategy would be realistic. Conversely, a reactive vaccine deployed in an outbreak context for ring-vaccination strategies should have rapid onset of protection with one dose, but longevity of protection is less important. In initial cases, before an outbreak is recognised, healthcare workers (HCWs) are at particular risk of acquiring and transmitting infection, thus potentially augmenting early epidemics. We hypothesise that many early outbreak cases could be averted, or epidemics aborted, by prophylactic vaccination of HCWs. This paper explores the potential impact of prophylactic versus reactive vaccination strategies of HCWs in preventing early epidemic transmissions. To do this, we use the limited data available from Ebola epidemics (current and historic) to reconstruct transmission trees and illustrate the theoretical impact of these vaccination strategies. Our data suggest a substantial potential benefit of prophylactic versus reactive vaccination of HCWs in preventing early transmissions. We estimate that prophylactic vaccination with a coverage >99% and theoretical 100% efficacy could avert nearly two-thirds of cases studied; 75% coverage would still confer clear benefit (40% cases averted), but reactive vaccination would be of less value in the early epidemic. A prophylactic vaccination campaign for front-line HCWs is not a trivial undertaking; whether to prioritise long-lasting vaccines and provide prophylaxis to HCWs is a live policy question. Prophylactic vaccination is likely to have a greater impact on the

Cost analysis of prophylactic intraoperative cystoscopic ureteral stents in gynecologic surgery.

Science.gov (United States)

Fanning, James; Fenton, Bradford; Jean, Geraldine Marie; Chae, Clara

2011-12-01

Prophylactic intraoperative ureteral stent placement is performed to decrease operative ureteric injury, though few data are available on the effectiveness of this procedure, and no data are available on its cost. To analyze the cost of prophylactic intraoperative cystoscopic ureteral stents in gynecologic surgery. All cases of prophylactic ureteral stent placement performed in gynecologic surgery during a 1-year period were identified and retrospectively reviewed through the electronic medical records database of Summa Health System. Costs were obtained through the Healthcare Cost Accounting System. The principles of cost-effective analysis were used (ie, explicit and detailed descriptions of costs and cost-effectiveness statistics). Importantly, we evaluated cost and not charges or financial model estimates. In addition, we obtained the contribution margins (ie, the hospital's net profit or loss) for prophylactic ureteral stent placement. Other gynecologic procedures were also analyzed. Among 792 major inpatient gynecologic procedures, 18 cases of prophylactic intraoperative ureteral stents were identified. Median costs were as follows: additional cost of prophylactic intraoperative ureteral stenting, $1580; additional cost of surgical resources, $770; cost of ureteral catheters, $427; cost of surgeons, $383. The contribution margins per case for various gynecologic surgical procedures were as follows: oophorectomy, $2804 profit; abdominal hysterectomy, $2649 profit; laparoscopically assisted vaginal hysterectomy (LAVH), $1760 profit. When intraoperative ureteral stenting was added, the contribution margins changed to the following: oophorectomy, $782 profit; abdominal hysterectomy, $627 profit; LAVH, $262 loss. Overall, the contribution margin profit was decreased by about 85%, from $2400 to $380. Prophylactic intraoperative ureteral stenting in gynecologic surgery decreases a hospital's contribution margin. Because of the expense of this procedure, as well as

Prophylactic treatment of migraine; the patient's view, a qualitative study

NARCIS (Netherlands)

Dekker, F.; Knuistingh Neven, A.; Andriesse, B.; Kernick, D.; Reis, R.; Ferrari, M.D.; Assendelft, W.J.J.

2012-01-01

BACKGROUND: Prophylactic treatment is an important but under-utilised option for the management of migraine. Patients and physicians appear to have reservations about initiating this treatment option. This paper explores the opinions, motives and expectations of patients regarding prophylactic

Prophylactic and thermovision measurements of electric machines and equipment

International Nuclear Information System (INIS)

Jedlicka, R.; Brestovansky, L.

1996-01-01

High-voltage measurements of generators, unit and service transformers and some significant motor drives used at a nuclear power plant are described in this paper. Thermovision measurements of electric machines and distribution systems are dealt with in the second part of the paper. Power electric equipment represent one of the most significant components of a nuclear power plant. Turbine mechanical energy is converted into the electrical energy within these equipment. Power generated by generators is transformed by transformers so that it can achieve appropriate parameters for both the transmission over the distribution system and the power plant service power supply. The service power supply switchboards and cables provide supply to motors and other consumers necessary for the nuclear power plant technological process. The whole complex of equipment has to be maintained in good technical conditions. It is necessary to make thermovision and prophylactic measurements to identify and verify the electric equipment technical condition. The mentioned measurements warn the operation staff in advance against both gradual deterioration of power connection contact resistances, i.e. power connections overheating, and the machine insulation systems condition deterioration. The operation staff try to prevent the electric equipment operation accidents by early removing the detected failures, thus, improving the nuclear safety. In order to provide the above-mentioned activities a special prophylactic measurement group was established at the NPP Bohunice in 1983. The group specialists make following types of measurements. 1. Prophylactic measurements of electric machines. Prophylactics of 220 MW generators and 6 MW service power generators; Prophylactics of both unit and service transformers and VHV bushings; Prophylactics of major 6 kV motor drives. 2. Thermovision measurements of current connections. Measurements enumarated in paragraph 1 are made on disconnected electric

Planning horizon affects prophylactic decision-making and epidemic dynamics.

Science.gov (United States)

Nardin, Luis G; Miller, Craig R; Ridenhour, Benjamin J; Krone, Stephen M; Joyce, Paul; Baumgaertner, Bert O

2016-01-01

The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon-the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals' payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individual's perceived risk of infection.

Role of microRNA Pathway in Mental Retardation

Science.gov (United States)

Qurashi, Abrar; Chang, Shuang; Jin, Peng

2007-01-01

Deficits in cognitive functions lead to mental retardation (MR). Understanding the genetic basis of inherited MR has provided insights into the pathogenesis of MR. Fragile X syndrome is one of the most common forms of inherited MR, caused by the loss of functional Fragile X Mental Retardation Protein (FMRP). MicroRNAs (miRNAs) are endogenous, single-stranded RNAs between 18 and 25 nucleotides in length, which have been implicated in diversified biological pathways. Recent studies have linked the miRNA pathway to fragile X syndrome. Here we review the role of the miRNA pathway in fragile X syndrome and discuss its implication in MR in general. PMID:17982588

Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis

Science.gov (United States)

Konstantopoulos, Aris; Tan, Xiao Wei; Goh, Gwendoline Tze Wei; Saraswathi, Padmanabhan; Chen, Liyan; Nyein, Chan Lwin; Zhou, Lei; Beuerman, Roger; Tan, Donald Tiang Hwee; Mehta, Jod

2015-01-01

Background Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2–17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model. Methodology Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7–12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits. Results On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of

Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.

Directory of Open Access Journals (Sweden)

Aris Konstantopoulos

Full Text Available Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model.Twenty-three rabbits were assigned either to a prophylactic group (n = 13 that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10 that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP, anterior segment optical coherence tomography (AS-OCT, and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits.On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively. On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71 on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml exceeded minimum inhibitory concentration (MIC for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops.Prophylactic

Cardiac disturbances after pneumonectomy--the value of prophylactic digitalization.

Science.gov (United States)

Järvinen, A; Mattila, T; Appelqvist, P; Meurala, H; Mattila, S

1978-01-01

The incidence of postoperative cardiac disturbances and the value of prophylactic digitalization were studied retrospectively in 143 patients undergoing pneumonectomy for carcinoma of the lung. Cardiac arrhythmias occurred in 29% and tachycardia episodes in 30% of the patients. The incidence of myocardial infarction was 2%. Operative mortality was 4%. The cardiac disturbances developed more often after left than after right pneumonectomy. The age of the patients, a history of angina pectoris or hypertension did not markedly increase the incidence of cardiac disturbances, neither did operative factors, such as pericardiotomy, left atrial resection, major bleeding nor postoperative empyema. Prophylactic digitalization significantly reduced postoperative cardiac disorders, their frequency being 33% in the group of patients who received prophylactic digitalis compared with 65% in the group that did not.

[Prophylactic treatments of migraine].

Science.gov (United States)

Massiou, H

2000-01-01

Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. It is usually proposed to patients who suffer from two or more attacks per month. It should also be considered in patients who suffer from less frequent, but prolonged, disabling attacks with a poor response to abortive treatment, and who consider that their quality of life is reduced between attacks. Excessive intake of acute medication, more than twice a week, is a strong indication for prophylactic treatment. In order to obtain a good compliance to treatment, the patient must be informed of the expected efficacy of the drugs, and of their most frequent side effects. Thus, the choice of a prophylactic drug is made together with the patient. Based on the results of published controlled trials, the main prophylactic drugs are some betablockers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, and sodium valproate. Some less evaluated drugs such as aspirin, DHE, indoramine, verapamil, may be useful. Other substances such as riboflavin and new antiepileptic dugs are being evaluated. The choice of the drug to start with depends on several considerations. The first step is to make sure that there are no contra indications, and no possible interaction with the abortive medications. Then, possible side effects will be taken into account, for example, weight gain is a problem for most young women and patients who practice sports may not tolerate betablockers. Associated pathologies have to be checked. For example, a hypertensive migraine sufferers may benefit from betablockers; in a patient who suffers both from migraine and tension type headaches or from depression, amitriptyline is the first choice drug. The type of migraine should also be considered; for instance, in frequent attacks with aura, aspirin is recommended and betablockers avoided. In most cases, prophylaxis should be given as monotherapy, and it is often necessary to try successively several drugs

Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD(50) yields insight into the efficacy of prophylactics.

Science.gov (United States)

Marziaz, Mandy L; Frazier, Kathryn; Guidry, Paul B; Ruiz, Robyn A; Petrikovics, Ilona; Haines, Donovan C

2013-01-01

Cyanide inhibits cytochrome c oxidase, the terminal oxidase of the mitochondrial respiratory pathway, therefore inhibiting the cell oxygen utilization and resulting in the condition of histotoxic anoxia. The enzyme rhodanese detoxifies cyanide by utilizing sulfur donors to convert cyanide to thiocyanate, and new and improved sulfur donors are actively sought as researchers seek to improve cyanide prophylactics. We have determined brain cytochrome c oxidase activity as a marker for cyanide exposure for mice pre-treated with various cyanide poisoning prophylactics, including sulfur donors thiosulfate (TS) and thiotaurine (TT3). Brain mitochondria were isolated by differential centrifugation, the outer mitochondrial membrane was disrupted by a maltoside detergent, and the decrease in absorbance at 550 nm as horse heart ferrocytochrome c (generated by the dithiothreitol reduction of ferricytochrome c) was oxidized was monitored. Overall, the TS control prophylactic treatment provided significant protection of the cytochrome c oxidase activity. The TT3-treated mice showed reduced cytochrome c oxidase activity even in the absence of cyanide. In both treatment series, addition of exogenous Rh did not significantly enhance the prevention of cytochrome c oxidase inhibition, but the addition of sodium nitrite did. These findings can lead to a better understanding of the protection mechanism by various cyanide antidotal systems. Copyright © 2011 John Wiley & Sons, Ltd.

The putative roles of the ubiquitin/proteasome pathway in resistance to anticancer therapy.

Science.gov (United States)

Smith, Laura; Lind, Michael J; Drew, Philip J; Cawkwell, Lynn

2007-11-01

The ubiquitin/proteasome (UP) pathway plays a significant role in many important biological functions and alterations in this pathway have been shown to contribute to the pathology of many human diseases, including cancer. Proteasome inhibition has been well established as a rational strategy for the treatment of multiple myeloma and is currently under investigation for the treatment of other haematological malignancies and solid tumours. Recent evidence suggests that proteasome inhibition may also sensitise tumour cells to the actions of both conventional chemotherapy and radiotherapy, suggesting that this pathway may modify clinical response to anticancer therapy. However, conflicting evidence exists as to the roles of the UP pathway in resistance to treatment. This review endeavours to discuss such roles.

The evolution of the pathway and its role in improving patient care.

Science.gov (United States)

Mould, G; Bowers, J; Ghattas, M

2010-10-01

Redesign in healthcare has increased the focus on the needs of the patient. The redesign process typically involves a review of current practice using the patient pathway before considering possible improvements. The patient pathway can serve various roles, and it may be mapped in different ways using a variety of media. This paper reviews the evolution of the patient pathway comparing the merits of different media. Simple approaches to mapping pathways can be most useful. However, experience in the redesign of Unscheduled Care in NHS Fife suggests that computer-based, hierarchical pathway models using stylised icons offer many advantages. Such approaches can increase the effectiveness of pathways in the redesign process, providing both the detail and the system view in an accessible graphical form. This enhanced capability helps staff analyse current practice and visualise and assess redesign options. In addition, the pathway can fulfil new roles as a training tool and an effective basis for organising knowledge about patient care.

Clinical course of preterm prelabor rupture of membranes in the era of prophylactic antibiotics

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Phupong Vorapong

2012-09-01

Full Text Available Abstract Background Preterm prelabor rupture of membrane (PPROM causes maternal and neonatal complications. Prophylactic antiobiotics were used in the management of PPROM. The objectives of this retrospective study were to compare clinical course and outcome of PPROM managed expectantly with prophylactic antibiotics and antenatal corticosteroids with those without prophylactic antibiotics and antenatal corticosteroids. Results A total of 170 cases of singleton pregnant women with gestational age between 28–34 weeks suffering from PROM during January 1998 to December 2009 were included; 119 cases received prophylactic antibiotics and antenatal corticosteroids while 51 cases did not received prophylactic antibiotics and antenatal corticosteroids. Median latency period in the study group was significantly longer than in the control group (89.8 vs. 24.3 hours, P  Conclusions Latency period of PPROM after using prophylactic antibiotics and antenatal corticosteroids increased while neonatal infectious morbidity was low. But maternal infectious morbidity was not increased. This retrospective study confirms the benefit of prophylactic antibiotics and antenatal corticosteroids in management of PPROM.

Prophylactic Antibiotics and Wound Infection

OpenAIRE

Elbur, Abubaker Ibrahim; M.A., Yousif; El-Sayed, Ahmed S.A.; Abdel-Rahman, Manar E.

2013-01-01

Introduction: Surgical site infections account for 14%-25% of all nosocomial infections. The main aims of this study were to audit the use of prophylactic antibiotic, to quantify the rate of post-operative wound infection, and to identify risk factors for its occurrence in general surgery.

Role of Membrane Biophysics in Alzheimer's - related cell pathways

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Donghui eZhu

2015-05-01

Full Text Available Cellular membrane alterations are commonly observed in many diseases, including Alzheimer’s disease (AD. Membrane biophysical properties, such as membrane molecular order, membrane fluidity, organization of lipid rafts, and adhesion between membrane and cytoskeleton, play an important role in various cellular activities and functions. While membrane biophysics impacts a broad range of cellular pathways, this review addresses the role of membrane biophysics in amyloid-β peptide aggregation, Aβ-induced oxidative pathways, amyloid precursor protein processing, and cerebral endothelial functions in AD. Understanding the mechanism(s underlying the effects of cell membrane properties on cellular processes should shed light on the development of new preventive and therapeutic strategies for this devastating disease.

Role of prophylactic surgical ligation of patent ductus arteriosus in extremely low birth weight infants: Systematic review and implications for clinical practice

International Nuclear Information System (INIS)

Mosalli, Rafat; AlFaleh, Khalid; Paes, Bosco

2009-01-01

To investigate the effectiveness and safety of prophylactic surgical ligation of patent ductus arteriosus (PDA) on mortality and morbidity of preterm infants weighing less than 1000 g at birth. The study conducted a systematic search of available database from 1996-2008. Retrieved articles were assessed for eligibility and data was abstracted independently by two reviewers. Decisions to include studies for review and the methodological quality of included studies were asssessed in duplicate based on predetermined criteria. No language restrictions were applied. Only one eligible study that enrolled 84 extremely low birth weight infants was identified. Prophylactic surgical ligation of PDA resulted in a statistically significant reduction of severe stage II or III necrotizing enterocolitis, [RR 0.25, 95% CI (0.08, 0.83), P value 0.02, number needed to treat 5]. The study, however, found no statistically significant difference in mortality, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity. Current evidence does not support the use of prophylactic surgical ligation of PDA in the management of the preterm infants

Low risk of perioperative infection without prophylactic antibiotics for transperineal prostate brachytherapy

International Nuclear Information System (INIS)

Wallner, Kent; Roy, Jitendra; Harrison, Louis

1996-01-01

Purpose: To determine the incidence of postimplant infection in patients who are not given prophylactic antibiotics (ATBs). Methods and Materials: One hundred thirty-one patients had computerized tomography (CT)-planned transperineal 125 I implantation of the prostate from 1988 through 1995. One hundred fourteen of the patients did not receive prophylactic ATBs, 19 of whom required postimplant Foley catheter drainage for 1 day or more for acute urinary retention. Results: The incidence of postimplant febrile episodes within 2 weeks of surgery among the patients who had not received prophylactic ATBs was 2 of 114 (2%). One of the two patients who developed postimplantation febrile episodes was treated successfully with ATBs as an outpatient. The second patient, who had a history of chronic lymphocytic leukemia (CLL) and immune suppression, developed E. coli sepsis and required intravenous antibiotics. Of 17 patients who received prophylactic ATBs, none had a postoperative febrile episode. Conclusion: We continue to refrain from routinely prescribing prophylactic ATBs unless there is some compelling circumstance including rheumatic heart disease, prosthetic devices, immune compromise, or a previous history of prostatitis

The emerging role of toll-like receptor pathways in surgical diseases.

LENUS (Irish Health Repository)

Romics, Laszlo Jr

2012-02-03

OBJECTIVE: To outline the emerging significance of Toll-like receptor (TLR) signaling pathways in surgical diseases. DATA SOURCES: A systematic review of the literature was undertaken by searching the MEDLINE database for the period 1966 to 2005 without language restriction. STUDY SELECTION: Original or review articles that described experimental data on the activation of TLR signaling pathways in surgically relevant diseases were selected for inclusion in this review. DATA EXTRACTION: Data were obtained from peer-reviewed articles and references. DATA SYNTHESIS: The role of TLRs in the recognition of pathogens renders them a key figure in the activation of both innate and adaptive immune responses during sepsis. However, emerging evidence points to fundamentally important roles in ulcerative colitis, Crohn disease, and Helicobacter pylori infection in the gastrointestinal tract and in the development of atherosclerotic plaques in the cardiovascular system. Furthermore, recent studies suggest that the regulation of the TLR pathway fulfills a central role in anticancer immunotherapy and in organ rejection after transplantation. CONCLUSION: Given the clinical significance of TLR pathways, the targeting of individual molecular components is likely to offer a broad range of future therapeutic modalities.

Prophylactic antidepressant treatment following acute coronary syndrome

DEFF Research Database (Denmark)

Christiansen, Ole G; Madsen, Michael T; Simonsen, Erik

2017-01-01

Major depressive disorder is significantly increased in patients following acute coronary syndrome resulting in twofold increased mortality compared with patients without depression. The depression diagnosis is often missed leading to considerable undertreatment. This systematic review assesses...... the current evidence of primary prophylactic treatment of depression in patients after acute coronary syndrome. The study protocol was prospectively registered at PROSPERO (registration number CRD42015025587). A systematic review were conducted and reported according to Preferred Reporting Items...... for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, PsychINFO, CINAHL, and Cochran Library was searched. Two independent reviewers screened the records. The inclusion criteria were randomized controlled trials on adult patients with acute coronary syndrome treated prophylactically...

Wnt/β-catenin pathway in tissue injury: roles in pathology and therapeutic opportunities for regeneration

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Bastakoty, Dikshya; Young, Pampee P.

2016-01-01

The Wnt/β-catenin pathway is an evolutionarily conserved set of signals with critical roles in embryonic and neonatal development across species. In mammals the pathway is quiescent in many organs. It is reactivated in response to injury and is reported to play complex and contrasting roles in promoting regeneration and fibrosis. We review the current understanding of the role of the Wnt/β-catenin pathway in injury of various mammalian organs and discuss the current advances and potential of Wnt inhibitory therapeutics toward promoting tissue regeneration and reducing fibrosis.—Bastakoty, D., Young, P. P. Wnt/β-catenin pathway in tissue injury: roles in pathology and therapeutic opportunities for regeneration. PMID:27335371

Prophylactic Role of Averrhoa carambola (Star Fruit) Extract against Chemically Induced Hepatocellular Carcinoma in Swiss Albino Mice.

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Singh, Ritu; Sharma, Jyoti; Goyal, P K

2014-01-01

Liver cancer remains one of the severe lethal malignancies worldwide and hepatocellular carcinoma (HCC) is the most common form. The current study was designed to evaluate the prophylactic role of the fruit of Averrhoa carambola (star fruit or Kamrak) on diethylnitrosamine- (DENA-) induced (15 mg/kg b.wt.; single i.p. injection) and CCl4-promoted (1.6 g/kg b.wt. in corn oil thrice a week for 24 weeks) liver cancer in Swiss albino mice. Administration of ACE was made orally at a dose of 25 mg/kg b.wt/day for 5 consecutive days and it was withdrawn 48 hrs before the first administration of DENA (preinitiational stage). CCl4 was given after 2 weeks of DENA administration. A cent percent tumor incidence was noted in carcinogen treated animals while ACE administration resulted in a considerable reduction in tumor incidence, tumor yield, and tumor burden. Further, ACE treatment brings out a significant reduction in lipid peroxidation (P carambola against hepatocellular carcinoma in mice; therefore, it could be employed for the further screening as a good chemopreventive natural supplement against cancer.

Modelling formulae of strawberry whey drinks of prophylactic application

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N. Tkachenko

2017-04-01

Full Text Available Expediency of the development of formulae and innovative technologies for production of prophylactic application drinks possessing antioxidant, probiotic and hepatoprotective properties with the use of the secondary dairy product – whey, as well as the domestic vegetable raw materials having a high content of bioactive substances has been substantiated.Formulation composition of the prophylactic drinks based on cheese whey, extract of Tagetes patula flowers and the berry filler “Strawberry” with the use of the response surface method has been developed. Bioactivity of the drinks and the complex quality indicator which accounts for the total influence of the bioactivity, organoleptic assessment and weight coefficients of the specified unit indicators were taken as the optimization criteria; as the independent factors that were varied in the course of the experiment, the mass fractions of the marigold flowers extract and the strawberries filler were selected. It is recommended that the mass fractions of the berry filler “Strawberry” and the extract of Tagetes patula flowers in the prophylactic drinks are set as 7 and 20 % of the finished product, accordingly. The practical mass fraction of the citric acid of 0.2 % was determined as it ensures high organoleptic characteristics of the finished drinks. Recommendations are given concerning development of innovative technologies of unfermented and fermented strawberry whey drinks of prophylactic application enriched with the extract of Tagetes patula flowers.

The Role of Prophylactic Ibuprofen and N-Acetylcysteine on the Level of Cytokines in Periapical Exudates and the Post-Treatment Pain

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Seyyed Mohsen Aghajanpour Mir

2012-09-01

Full Text Available Background Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive-microbial disturbances. Objective:To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC on the levels of tumor necrosis factor alpha (TNF- alpha, interleukin- 6(IL-6 and IL-17 and post-treatment pain level in chronic periapical lesions. Materials and methods Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg, ibuprofen tablets (400 mg, NAC (400 mg/ibuprofen (200 mg combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- alpha, IL-6 and IL-17 levels were determined by ELISA and posttreatment pain was assessed using a visual analog scale (VAS. Results:There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019. Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043. Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017. Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033. After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049. Conclusion:The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain

The role of prophylactic ibuprofen and N-acetylcysteine on the level of cytokines in periapical exudates and the post-treatment pain

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Ehsani Maryam

2012-09-01

Full Text Available Abstract Background Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive–microbial disturbances. Objective To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC on the levels of tumor necrosis factor alpha (TNF- α, interleukin- 6(IL-6 and IL-17 and post-treatment pain level in chronic periapical lesions. Materials and methods Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg, ibuprofen tablets (400 mg, NAC (400 mg/ibuprofen (200 mg combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- α, IL-6 and IL-17 levels were determined by ELISA and post-treatment pain was assessed using a visual analog scale (VAS. Results There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019. Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043. Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017. Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033. After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049. Conclusion The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain.

Effect of prophylactic CPAP in very low birth weight infants in South America.

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Zubizarreta, J R; Lorch, S A; Marshall, G; D'Apremont, I; Tapia, J L

2016-08-01

The objective of this study was to examine the effect of prophylactic continuous positive airway pressure (CPAP) on infants born in 25 South American neonatal intensive care units affiliated with the Neocosur Neonatal Network using novel multivariate matching methods. A prospective cohort was constructed of infants with a birth weight 500 to 1500 g born between 2005 and 2011 who clinically were eligible for prophylactic CPAP. Patients who received prophylactic CPAP were matched to those who did not on 23 clinical and sociodemographic variables (N=1268). Outcomes were analyzed using the McNemar's test. Infants not receiving prophylactic CPAP had higher mortality rates (odds ratio (OR)=1.69, 95% confidence interval (CI) 1.17, 2.46), need for any mechanical ventilation (OR=1.68, 95% CI 1.33, 2.14) and death or bronchopulmonary dysplasia (BPD) (OR=1.47, 95% CI 1.09, 1.98). The benefit of prophylactic CPAP varied by birth weight and gender. The implementation of this process was associated with a significant improvement in survival and survival free of BPD.

Factors Associated With the Prophylactic Prescription of a Bowel Regimen to Prevent Opioid-Induced Constipation.

Science.gov (United States)

Chen, Nancy Y; Nguyen, Eugene; Schrager, Sheree M; Russell, Christopher J

2016-11-01

Identify factors associated with the prophylactic prescription of a bowel regimen with an inpatient opioid prescription. This was a retrospective cohort study from June 1, 2013, to October 31, 2014 of pediatric inpatients prescribed an oral or intravenous opioid on the general medical/surgical floors. We identified patients with or without a prophylactic prescription of a bowel regimen. We obtained patient demographics, prescriber training level and service and used multivariate logistic regression to analyze the factors associated with prophylactic bowel regimen and opioid prescription. Of the 6682 encounters that met study criteria, only 966 (14.5%) encounters had prophylactic prescriptions. Patient factors associated with prophylactic prescription include increasing age (per year; odds ratio [OR] = 1.06, 95% confidence interval [CI] 1.05-1.07) and sickle cell diagnosis (OR = 3.19, 95% CI 2.08-4.91). Medication factors associated with prophylactic prescription include a scheduled opioid prescription (OR = 1.75, 95% CI 1.46-2.1) and a prescription for oxycodone (OR = 3.59, 95% CI 2.57-5.00) or morphine (OR = 1.84, 95% CI 1.39-2.44), compared with acetaminophen-hydrocodone. Compared with medical providers, surgeons were less likely (OR = 0.43, 95% CI 0.35-0.53) and pain service providers were more likely to prescribe a prophylactic bowel regimen (OR = 4.12, 95% CI 3.13-5.43). More than 85% of inpatient opioid prescriptions did not receive a prophylactic bowel regimen. Future research should examine factors (eg, clinical decision support tools) to increase prophylactic prescription of bowel regimens with opioids for populations found to have lower rates. Copyright © 2016 by the American Academy of Pediatrics.

Prophylactic treatment of migraine; the patient's view, a qualitative study

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Dekker Frans

2012-03-01

Full Text Available Abstract Background Prophylactic treatment is an important but under-utilised option for the management of migraine. Patients and physicians appear to have reservations about initiating this treatment option. This paper explores the opinions, motives and expectations of patients regarding prophylactic migraine therapy. Methods A qualitative focus group study in general practice in the Netherlands with twenty patients recruited from urban and rural general practices. Three focus group meetings were held with 6-7 migraine patients per group (2 female and 1 male group. All participants were migraine patients according to the IHS (International Headache Society; 9 had experience with prophylactic medication. The focus group meetings were analysed using a general thematic analysis. Results For patients several distinguished factors count when making a decision on prophylactic treatment. The decision of a patient on prophylactic medication is depending on experience and perspectives, grouped into five categories, namely the context of being active or passive in taking the initiative to start prophylaxis; assessing the advantages and disadvantages of prophylaxis; satisfaction with current migraine treatment; the relationship with the physician and the feeling to be heard; and previous steps taken to prevent migraine. Conclusion In addition to the functional impact of migraine, the decision to start prophylaxis is based on a complex of considerations from the patient's perspective (e.g. perceived burden of migraine, expected benefits or disadvantages, interaction with relatives, colleagues and physician. Therefore, when advising migraine patients about prophylaxis, their opinions should be taken into account. Patients need to be open to advice and information and intervention have to be offered at an appropriate moment in the course of migraine.

PASS Student Leader and Mentor Roles: A Tertiary Leadership Pathway

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Skalicky, Jane; Caney, Annaliese

2010-01-01

In relation to developing leadership skills during tertiary studies, this paper considers the leadership pathway afforded by a Peer Assisted Study Sessions (PASS) program which includes the traditional PASS Leader role and a more senior PASS Mentor role. Data was collected using a structured survey with open-ended questions designed to capture the…

Pressure ulcer prevention and treatment: use of prophylactic dressings

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Reid K

2016-10-01

Full Text Available Kathleen Reid,1 Elizabeth A Ayello,2 Afsaneh Alavi,3 1Department of Nursing Practice and Education, Bridgepoint Active Healthcare, Toronto, Canada; 2School of Nursing, Excelsior College, Albany, NY, USA; 3Department of Medicine, University of Toronto, Toronto, Canada Abstract: The management of pressure ulcers is challenging for health care providers across disciplines. Pressure ulcers have significant impact on emotional and physical wellbeing, quality of life, and health care costs. The use of wound dressings could be an important and cost-effective strategy in preventing pressure ulcers. The main types of dressings that are examined for this purpose in the literature are foam, hydrocolloid, and films. Some small studies have shown a preventative role for sacral dressings with low-shear backings, though they raise concerns about over-hydration of the skin. Further research demonstrates the application of barrier films over bony prominences to have a prophylactic effect; however, adhesive dressings can also contribute to shearing forces on the skin. There is a vast body of research that examines the use of dressings to prevent pressure ulcers; however, there is limited high-level evidence, such as randomized control trials. A 2013 Cochrane review indicated that there is a paucity of high-level evidence to support the prophylactic use of dressings to prevent pressure ulcers; this paper will examine the emerging literature and consider its relevance to pressure ulcer prevention protocols. Keywords: quality of life, hydrocolloid dressing, topical agent

Is there a role for prophylactic colectomy in Lynch syndrome patients with inflammatory bowel disease?

Science.gov (United States)

McNamara, Kate L; Aronson, Melyssa D; Cohen, Zane

2016-01-01

Lynch syndrome and chronic inflammatory bowel disease are two important risk factors for colorectal cancer. It is unclear whether Lynch syndrome patients with inflammatory bowel disease are at sufficiently increased risk for colorectal cancer to warrant prophylactic colectomy. This study aims to identify all cases of Lynch syndrome and concurrent inflammatory bowel disease in a large familial gastrointestinal cancer registry, define incidence of colorectal cancer, and characterize mismatch repair protein gene mutation status and inflammatory bowel disease-associated colorectal cancer risk factors. We retrospectively identified and collected clinical data for all cases with confirmed diagnoses of Lynch syndrome and inflammatory bowel disease in the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital in Toronto, Canada. Twelve cases of confirmed Lynch syndrome, and concurrent inflammatory bowel disease were identified. Four cases developed colorectal cancer. An additional five cases had colectomy; one was performed for severe colitis, and four were performed for low-grade dysplasia. None of these surgical specimens contained malignancy or high-grade dysplasia. The presentation of Lynch syndrome with inflammatory bowel disease is uncommon and not well described in the literature. This small but important series of twelve cases is the largest reported to date. In this series, patients with Lynch syndrome and concurrent inflammatory bowel disease do not appear to have sufficiently increased risk for colorectal cancer to recommend prophylactic surgery. Therefore, the decision to surgery should continue to be guided by surgical indications for each disease. Further evaluation of this important area will require multi-institutional input.

Benefits of prophylactic gastropexy for dogs at risk of gastric dilatation-volvulus.

Science.gov (United States)

Ward, Michael P; Patronek, Gary J; Glickman, Lawrence T

2003-09-12

The lifetime probability of death from gastric dilation-volvulus (GDV) for five dog breeds was estimated based on published breed-specific longevity and GDV incidence. These breeds were Great Dane, Irish Setter, Rottweiler, Standard Poodle and Weimaraner. Lifetime risk (95% CI) of GDV in these breeds ranged from 3.9% (0-11.2%) for Rottweiler to 36.7% (25.2-44.6%) for Great Dane. A decision-tree analysis for prophylactic gastropexy--using lifetime probability of death from GDV and expected cost savings for veterinary services as outcome measures--was undertaken to determine the preferred course of action in several dog breeds. Prophylactic gastropexy was the preferred choice of action for all breeds examined, with the reduction in mortality (versus no gastropexy) ranging from 2.2-fold (Rottweiler) to 29.6-fold (Great Dane). Assuming a prophylactic gastropexy costs US$ 400, the procedure was cost-effective when the lifetime risk of GDV was > or = 34%. The maximum and minimum estimated breakeven costs for the gastopexy procedure ranged from US$ 20 (Rottweiler) to US$ 435 (Great Dane). The cost-effectiveness of prophylactic gastropexy was most sensitive to the cost of treating GDV (US$ 1500). Prophylactic gastropexy raises ethical issues that need to be considered by veterinarians and dog breeders.

Usage of prophylactic radiologically inserted gastrostomy in head and neck cancer patients

International Nuclear Information System (INIS)

Mallinson, P.I.; Tun, J. Kyaw; Byass, O.R.; Cast, J.E.I.

2012-01-01

Aim: To assess outcomes and usage rate of prophylactic radiologically inserted gastrostomy (RIG) in head and neck cancer (HNC) patients. Materials and methods: Outcome data of all HNC patients who underwent prophylactic RIG over a 22-month period (November 2007 to September 2009) in a tertiary referral centre were collected retrospectively. Thirty-day mortality, major and minor complication rates, and subsequent usage of the RIG were analysed. Results: Fifty-one HNC patients underwent prophylactic RIG. Three minor and no major immediate complications were identified. Sixteen minor and three major complications at 30-days were identified. Three (5.9%) major complications were identified. There was one death due to disease progression and not RIG insertion. The RIG was not used in 17.7% of patients post-procedure. Conclusion: Prophylactic RIG in HNC patients has a comparable mortality rate to RIG insertion in HNC patients with mixed indications. However, the number of cases where the gastrostomy is not used raises important concerns and warrants further investigation.

Effects of prophylactic antibiotics on wound infection in elective laparoscopic cholecystectomy

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Hamid Reza Hemati

2008-11-01

Full Text Available Introduction: Wound infection is one of the most common complications of surgical procedures.At present, different procedures are used to reduce wound infection including prophylactic antibiotics.Since laparoscopy controls the most sources of wound infection such as mechanical factors, the role ofprophylactic antibiotic therapy may be in doubt. In this study, we evaluated the antibiotic effects inprevention of wound infection in laparoscopic cholecystectomy.Methods and Materials: In this double-blind clinical trial study, patients who were candidate forlaparoscopic cholecystectomy were divided randomly into two groups: antibiotic receivers (38patients and placebo (Normal Saline receivers (32 patients group. The patients were visited in 24hours, 4-7, 10-15 and 30 days after surgery for wound infection and then 2 groups compared.Results: The study showed that there were no significant differences between two groups withrespect to age, body mass index and smoking. In addition, no wound infection was observed in first 24hours, 4-7, 10-15 and 30 days after operation in both groups.Conclusion: The findings showed that prophylactic antibiotic therapy in laparoscopiccholecystectomy has no effect on the incidence of wound infection. Therefore, it is suggested thatprophylactic antibiotic therapy does not use in laparoscopic cholecystectomy because of producingantibiotic resistance, unnecessary complications and also reducing economical costs.

Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A

NARCIS (Netherlands)

Collins, P. W.; Blanchette, V. S.; Fischer, K.; Bjorkman, S.; Oh, M.; Fritsch, S.; Schroth, P.; Spotts, G.; Astermark, J.; Ewenstein, B.

Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level <1 IU dL(-1).

Prophylactic antibiotics for endoscopy-associated peritonitis in peritoneal dialysis patients.

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Hsin-Hsu Wu

Full Text Available INTRODUCTION: Continuous ambulatory peritoneal dialysis (CAPD peritonitis may develop after endoscopic procedures, and the benefit of prophylactic antibiotics is unclear. In the present study, we investigated whether prophylactic antibiotics reduce the incidence of peritonitis in these patients. PATIENTS AND METHODS: We retrospectively reviewed all endoscopic procedures, including esophagogastroduodenoscopy (EGD, colonoscopy, sigmoidoscopy, cystoscopy, hysteroscopy, and hysteroscopy-assisted intrauterine device (IUD implantation/removal, performed in CAPD patients at Chang Gung Memorial Hospital, Taiwan, between February 2001 and February 2012. RESULTS: Four hundred and thirty-three patients were enrolled, and 125 endoscopies were performed in 45 patients. Eight (6.4% peritonitis episodes developed after the examination. Antibiotics were used in 26 procedures, and none of the patients had peritonitis (0% vs. 8.1% without antibiotic use; p=0.20. The peritonitis rate was significantly higher in the non-EGD group than in the EGD group (15.9% [7/44] vs. 1.2% [1/81]; p<0.005. Antibiotic use prior to non-EGD examinations significantly reduced the endoscopy-associated peritonitis rate compared to that without antibiotic use (0% [0/16] vs. 25% [7/28]; p<0.05. Peritonitis only occurred if invasive procedures were performed, such as biopsy, polypectomy, or IUD implantation, (noninvasive procedures, 0% [0/20] vs. invasive procedures, 30.4% [7/23]; p<0.05. No peritonitis was noted if antibiotics were used prior to examination with invasive procedures (0% [0/10] vs. 53.8% [7/13] without antibiotic use; p<0.05. Although not statistically significant, antibiotics may play a role in preventing gynecologic procedure-related peritonitis (antibiotics, 0% [0/4] vs. no antibiotics, 55.6% [5/9]; p=0.10. CONCLUSION: Antibiotic prophylaxis significantly reduced endoscopy-associated PD peritonitis in the non-EGD group. Endoscopically assisted invasive procedures, such

The role of prophylactic cefazolin in the prevention of infection after various types of abdominal wall hernia repair with mesh

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Mostafa Mehrabi Bahar

2015-07-01

Conclusion: Preoperative administration of single-dose cefazolin for prosthetic hernia repairs did not markedly decrease the risk of wound infection. Our results do not support the use of cefazolin as a prophylactic antibiotic for various kinds of abdominal wall hernia repair with mesh.

Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study.

Science.gov (United States)

Coors, Sarah M; Cousin, Joshua J; Hagan, Joseph L; Kaiser, Jeffrey R

2018-03-28

To test the hypothesis that prophylactic dextrose gel administered to newborn infants at risk for hypoglycemia will increase the initial blood glucose concentration after the first feeding and decrease neonatal intensive care unit (NICU) admissions for treatment of asymptomatic neonatal hypoglycemia compared with feedings alone. This quasi-experimental study allocated asymptomatic at-risk newborn infants (late preterm, birth weight 4000 g, and infants of mothers with diabetes) to receive prophylactic dextrose gel (Insta-Glucose; Valeant Pharmaceuticals North America LLC, Bridgewater, New Jersey); other at-risk infants formed the control group. After the initial feeding, the prophylactic group received dextrose gel (0.5 mL/kg) rubbed into the buccal mucosa. The blood glucose concentration was checked 30 minutes later. Initial glucose concentrations and rate of NICU admissions were compared between the prophylactic group and controls using bivariate analyses. A multivariable linear regression compared first glucose concentrations between groups, adjusting for at-risk categories and age at first glucose concentration. There were 236 subjects (72 prophylactic, 164 controls). The first glucose concentration was not different between the prophylactic and control groups in bivariate analysis (52.1 ± 17.1 vs 50.5 ± 15.3 mg/dL, P = .69) and after adjusting for covariates (P  = .18). Rates of NICU admission for treatment of transient neonatal hypoglycemia were 9.7% and 14.6%, respectively (P = .40). Prophylactic dextrose gel did not reduce transient neonatal hypoglycemia or NICU admissions for hypoglycemia. The carbohydrate concentration of Insta-Glucose (77%) may have caused a hyperinsulinemic response, or alternatively, exogenous enteral dextrose influences glucose homeostasis minimally during the first few hours when counter-regulatory mechanisms are especially active. ClinicalTrials.gov: NCT02523222. Copyright © 2018 Elsevier Inc. All

Practice guideline on prophylactic cranial irradiation in small-cell lung cancer

International Nuclear Information System (INIS)

Kotalik, Jaro; Yu, Edward; Markman, Barbara R.; Evans, William K.

2001-01-01

Purpose: To develop an evidence-based clinical practice guideline that would address the following questions: (a) What is the role of prophylactic cranial irradiation (PCI) in patients with limited or extensive stage small-cell lung cancer (SCLC) who have achieved complete remission in response to induction therapy (chemotherapy or chemoradiotherapy)? (b) What dose and fractionation schedules of PCI are optimal? (c) Does the use of PCI in patients with SCLC in complete remission affect quality of life? Survival, disease-free survival, quality of life, and adverse effects were the outcomes of interest. Methods and Materials: A systematic review of the published literature was undertaken to provide the data for an evidence-based practice guideline. Results: Six randomized controlled trials and one fully published individual patient data meta-analysis were included in the systematic review of the evidence. For patients who have achieved complete response after induction therapy, there is evidence of a disease-free survival benefit (4 of 6 trials) and an overall survival benefit (meta-analysis). There is insufficient evidence to make a definitive recommendation with respect to dose. There is some indication that 30-36 Gy in 2-3 Gy per fraction, or a biologically equivalent dose, may produce a better outcome than a lower dose or less aggressive fractionation regimen. The schedule commonly used in Canada is 25 Gy in 10 fractions over 2 weeks. Data from further research, including a trial currently ongoing that compares 25 Gy in 10 fractions with 36 Gy in 18 fractions, will be required to determine optimal dose of PCI. There is insufficient evidence to make recommendations concerning the optimal timing of PCI in relation to the administration of chemotherapy. Lung DSG members generally felt that it should be given as soon as possible after completion of chemotherapy. There is evidence from trials with data for up to 2 years of follow-up that prophylactic cranial

[Prophylactic and therapeutic vaccines against human papilloma virus].

Science.gov (United States)

Albers, A E; Hoffmann, T K; Klussmann, J P; Kaufmann, A M

2010-08-01

Infection with human papilloma virus (HPV) has been identified as the cause of recurrent papillomatosis and of a subgroup of squamous cell carcinomas of the head and neck. A change in prevalence of these lesions, especially for oropharyngeal carcinoma, can be expected as a consequence of the introduction of prophylactic HPV vaccines for young women, targeting the most frequent high- and low-risk HPV subtypes. Vaccination for the major low-risk HPV types has proven to be highly effective against genital warts and activity against papillomatosis can be expected. The possibilities of prophylactic HPV vaccination as well as new developments and the rationale for therapeutic vaccines are discussed on the basis of the current literature.

[Effects of prophylactic chemotherapy on outcomes and prognosis of patients older than 40 years with invasive mole].

Science.gov (United States)

Jiang, S Y; Li, L; Zhao, J; Xiang, Y; Wan, X R; Feng, F Z; Ren, T; Yang, J J

2017-06-25

Objective: To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients. Methods: One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group, while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group). The general clinical data (including age, clinical stage, risk factor score), treatment, outcomes and relapse of patients were retrospectively compared between two groups. Results: (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old. Ratio of clinical stageⅠ-Ⅱ were 3/11 versus 29.8% (31/104), clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2% (73/104). Ratio of risk factor score 0-6 were 11/11 versus 84.6% (88/104), risk factor score >6 were 0 versus 15.4% (16/104). There were no significant statistical differences between two groups in age, clinical stage or risk factor score (all P> 0.05). (2) Treatment: the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different ( Z= 3.071, P= 0.002). There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of β-hCG, consolidation chemotherapy courses, total therapeutic chemotherapy courses or ratio of hysterectomy (all P> 0.05). (3) Outcomes and relapse: between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group, the complete remission rate were 11/11 versus 98.1%(102/104), the relapse rate were 0 versus 1.0%(1/102). There were no significant difference between the two groups in outcomes or relapse rate ( P> 0.05). Conclusions: Prophylactic chemotherapy does not substantially

Efficacy of postoperative prophylactic antibiotics in reducing permanent pacemaker infections.

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Lee, Wen-Huang; Huang, Ting-Chun; Lin, Li-Jen; Lee, Po-Tseng; Lin, Chih-Chan; Lee, Cheng-Han; Chao, Ting-Hsing; Li, Yi-Heng; Chen, Ju-Yi

2017-08-01

Despite limited evidence, postoperative prophylactic antibiotics are often used in the setting of permanent pacemaker implantation or replacement. The aim of this study is to investigate the efficacy of postoperative antibiotics. Postoperative prophylactic antibiotics may be not clinically useful. We recruited 367 consecutive patients undergoing permanent pacemaker implantation or generator replacement at a tertiary referral center. Baseline demographics, clinical characteristics, and procedure information were collected, and all patients received preoperative prophylactic antibiotics. Postoperative prophylactic antibiotics were administered at the discretion of the treating physician, and all patients were seen in follow-up every 3 to 6 months for an average follow-up period of 16 months. The primary endpoint was device-related infection. A total of 110 patients were treated with preoperative antibiotics only (group 1), whereas 257 patients received both preoperative and postoperative antibiotics (group 2). After a mean follow-up period of 16 months, 1 patient in group 1 (0.9%) and 4 patients in group 2 (1.5%) experienced a device-related infection. There was no significant difference in the rate of infection between the 2 groups (P = 0.624). In the univariate analysis, only the age (60 ± 11 vs 75 ± 12 years, P antibiotics had a similar rate of infection as those treated with preoperative antibiotics alone. Further studies are needed to confirm these preliminary findings. © 2017 Wiley Periodicals, Inc.

Should patients with Björk-Shiley valves undergo prophylactic replacement?

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Birkmeyer, J D; Marrin, C A; O'Connor, G T

1992-08-29

About 85,000 patients have undergone replacement of diseased heart valves with prosthetic Björk-Shiley convexo-concave (CC) valves. These valves are prone to fracture of the outlet strut, which leads to acute valve failure that is usually fatal. Should patients with these valves undergo prophylactic replacement to avoid fracture? The incidence of strut fracture varies between 0% and 1.5% per year, depending on valve opening angle (60 degrees or 70 degrees), diameter (less than 29 mm or greater than or equal to 29 mm), and location (aortic or mitral). Other factors include the patient's life expectancy and the expected morbidity and mortality associated with reoperation. We have used decision analysis to identify the patients most likely to benefit from prophylactic reoperation. The incidence of outlet strut fracture was estimated from the data of three large studies on CC valves, and stratified by opening angle, diameter, and location. A Markov decision analysis model was used to estimate life expectancy for patients undergoing prophylactic valve replacement and for those not undergoing reoperation. Prophylactic valve replacement does not benefit patients with CC valves that have low strut fracture risks (60 degrees aortic valves and less than 29 mm, 60 degrees mitral valves). For most patients with CC valves that have high strut fracture risks (greater than or equal to 29 mm, 70 degrees CC), prophylactic valve replacement increases life expectancy. However, elderly patients with such valves benefit from prophylactic reoperation only if the risk of operative mortality is low. Patient age and operative risk are most important in recommendations for patients with CC valves that have intermediate strut fracture risks (less than 29 mm, 70 degrees valves and greater than or equal to 29 mm, 60 degrees mitral valves). For all patients and their doctors facing the difficult decision on whether to replace CC valves, individual estimates of operative mortality risk that

[Therapeutic-prophylactic milk products with a new immunocorrector of natural origin].

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Besednova, N N; Epshteĭn, L M; Gazha, A K; Borovskaia, G A; Besednov, A L; Rozhzhov, I V; Smolina, T P

1997-01-01

Authors had received and investigated on experiment milk medical and prophylactic products (milk and kefir) with addition peptide, obtained from nervous tissue of squids. It has been established that addition of gangliin to the milk and kefir causes stimulation cellular and humoral factors of immunity answer at laboratory animals. Medical and prophylactic milk products with gangliin return to the normal state reduced immunity indexes of the mice with experimental immunodeficits.

Prophylactic central lymph nodes dissection (VI level in papillary thyroid cancer

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Pavel Olegovich Rumiantsev

2015-05-01

Full Text Available Metastatic involvement of central lymph nodes in patients with papillary thyroid cancer (PTC is very common. However, prophylactic central lymph nodes dissection additionally to thyroidectomy does not significantly affect disease-free and overall survival of PTC patients. Meanwhile its routine conduction is tangibly increase postsurgical complications. From efficacy/safety point of view prophylactic central lymph nodes dissection couldn't be recommended as substantiated in all PTC patients.

[Role of mitochondrial alternative oxidase (AOX) pathway in photoprotection in Rumex K-1 leaves].

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Meng, Xiang-Long; Zhang, Li-Tao; Zhang, Zi-Shan; Gao, Hui-Yuan; Meng, Qing-Wei

2012-07-01

Taking Rumex K-1 leaves as test materials, this paper studied the role of mitochondrial alternative oxidase (AOX) pathway in photoprotection under different light intensities. Under low light intensity (200 micromol x m(-2) x s(-1)), and after treated with salicylhydroxamic acid to inhibit the AOX pathway, the leaf actual photochemical efficiency of PS II, linear electron transport rate of photosynthesis, and photosynthetic O2 evolution rate all decreased significantly while the non-Q(B) reducing reaction center had a significant increase, indicating that under low light, the photoinhibition was aggravated while the scavenging enzymes of reactive oxygen species (ROS) increased, which avoided the over-accumulation of ROS and partially alleviated the photoinhibition of Rumex K-1 leaves. Under high light intensity (800 micromol x m(-2) x s(-1)), the inhibition of AOX pathway caused more severe photoinhibition, and the increased activities of ROS scavenging enzymes were insufficient to prevent the over-accumulation of ROS. This study demonstrated that AOX pathway played an important role in the photoprotection in Rumex K-1 leaves under both high and low light intensities, and the role of AOX pathway in photoprotection under high light could be irreplaceable by the other photoprotection pathways in chloroplast.

The use of prophylactic antibiotics in plastic surgery: update in 2010.

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Hauck, Randy M; Nogan, Stephen

2013-01-01

The indications for prophylactic antibiotics in plastic surgery remain controversial. No recent survey has been reported on the use of prophylactic antibiotics by plastic surgeons in clinical practice. This survey was designed to assess the current use of prophylactic antibiotics by plastic surgeons and to compare trends with previous studies. All members of the American Society of Plastic Surgeons with an e-mail address on the Society's website were contacted via an e-mail and sent a link to a SurveyMonkey questionnaire. To survey only in those subspecialty areas that they practice in, surgeons were queried only on the procedures that they perform. Within each section, a list of common representative procedures was included, with questions about the use of antibiotic prophylaxis. A total of 3824 American Society of Plastic Surgeons members were contacted. Of the 3613, 910 with working e-mail addresses responded to the survey for a response rate of 25%. And 833 or 91.5% completed the survey. Survey data cover the percentage of surgeons reporting their use of antibiotics in procedures that they currently perform. The percentage of plastic surgeons who use prophylactic antibiotics in almost all procedures studied has increased significantly when compared with earlier studies. The use of prophylactic antibiotics by plastic surgeons has increased considerably since the prior studies by Krizek et al (Plast Reconstr Surg. 1975;55:21-32 and 1985;76:953-963). Some of these uses are appropriate because of the use in procedures involving implants and longer operations. The elevated rates for clean procedures are not part of the evidence-based practice.

Prophylactic Anticonvulsants in patients with brain tumour

International Nuclear Information System (INIS)

Forsyth, P.A.; Weaver, S.; Fulton, D.

2003-01-01

We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need ≥900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

Prophylactic Anticonvulsants in patients with brain tumour

Energy Technology Data Exchange (ETDEWEB)

Forsyth, P.A. [Depts. of Oncology and Clinical Neurosciences, Univ. of Calgary, Calgary, Alberta (Canada); Tom Baker Cancer Centre, Calgary, Alberta (Canada); Weaver, S. [Depts. of Neurology and Medicine, Albany Medical College, Albany, New York (United States); Fulton, D. [Dept. of Radiation Oncology, Cross Cancer Institute and Dept. of Medicine/Neurology, Univ. of Alberta, Edmonton, Alberta (Canada)

2003-05-01

We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need {>=}900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

3D MODELLING OF PROPHYLACTIC FOOTWEAR FOR A HIGH ARCHED FOOT

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COSTEA Mariana

2016-05-01

Full Text Available This article approaches the methodology of designing customized footwear for high arched foot. The authors propose to reconsider the classical structure of footwear bottom components for people with high arched foot and recommend incorporating custom components, with the role of compensation or adjustment. This study continues the authors’ research, starting from a foot’s 3D shape obtained by 3D scanning, the anthropometrical and biomechanical parameters, shoe lasts’ 3D modelling and continuing with 3D footwear design. Including customized orthosis can help to stop the evolution of abnormalities, diminishes sensations of pain during walking and improves performance in various physical activities carried out during the day, walking, running, and standing. The prophylactic footwear has to meet four main requirements: to protect the foot and ankle during walking and static; to ensure the normal resistance systems (bones, muscle and joint of the foot; to prevent the installation of irreversible structural changes by reducing stress on the foot; to contribute to increased performance in conducting regular physical activity. It is presented the steps of modelling an orthosis, a virtual simulation of its cutting process, followed by the integration and development of the insole, filling and sole for a customized shoe. Delcam Crispin CAD system and its applications for orthopaedics are used to design the bottom components of prophylactic footwear for a high arched foot.

DMPD: A pervasive role of ubiquitin conjugation in activation and termination ofIkappaB kinase pathways. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15809659 A pervasive role of ubiquitin conjugation in activation and termination of...csml) Show A pervasive role of ubiquitin conjugation in activation and termination ofIkappaB kinase pathways.... PubmedID 15809659 Title A pervasive role of ubiquitin conjugation in activation and termina

Sex and hedgehog: roles of genes in the hedgehog signaling pathway in mammalian sexual differentiation.

Science.gov (United States)

Franco, Heather L; Yao, Humphrey H-C

2012-01-01

The chromosome status of the mammalian embryo initiates a multistage process of sexual development in which the bipotential reproductive system establishes itself as either male or female. These events are governed by intricate cell-cell and interorgan communication that is regulated by multiple signaling pathways. The hedgehog signaling pathway was originally identified for its key role in the development of Drosophila, but is now recognized as a critical developmental regulator in many species, including humans. In addition to its developmental roles, the hedgehog signaling pathway also modulates adult organ function, and misregulation of this pathway often leads to diseases, such as cancer. The hedgehog signaling pathway acts through its morphogenetic ligands that signal from ligand-producing cells to target cells over a specified distance. The target cells then respond in a graded manner based on the concentration of the ligands that they are exposed to. Through this unique mechanism of action, the hedgehog signaling pathway elicits cell fate determination, epithelial-mesenchymal interactions, and cellular homeostasis. Here, we review current findings on the roles of hedgehog signaling in the sexually dimorphic development of the reproductive organs with an emphasis on mammals and comparative evidence in other species.

The influence of prophylactic factor VIII in severe hemophilia A

Science.gov (United States)

Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

2013-01-01

Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

Prophylactic immunoglobulin therapy in secondary immune deficiency

DEFF Research Database (Denmark)

Agostini, Carlo; Blau, Igor-Wolfgang; Kimby, Eva

2016-01-01

RT in secondary immune deficiencies (SID), and most published guidelines are mere extrapolations from the experience in PID. AREAS COVERED: In this article, four European experts provide their consolidated opinion on open questions surrounding the prophylactic use of IgRT in SID, based on their clinical...

Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage.

Science.gov (United States)

Westhoff, Gina; Cotter, Amanda M; Tolosa, Jorge E

2013-10-30

Active management of the third stage of labour has been shown to reduce the risk of postpartum haemorrhage (PPH) greater than 1000 mL. One aspect of the active management protocol is the administration of prophylactic uterotonics, however, the type of uterotonic, dose, and route of administration vary across the globe and may have an impact on maternal outcomes. To determine the effectiveness of prophylactic oxytocin at any dose to prevent PPH and other adverse maternal outcomes related to the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013). Randomised or quasi-randomised controlled trials including pregnant women anticipating a vaginal delivery where prophylactic oxytocin was given during management of the third stage of labour. The primary outcomes were blood loss > 500 mL and the use of therapeutic uterotonics. Two review authors independently assessed trials for inclusion, assessed trial quality and extracted data. Data were checked for accuracy. This updated review included 20 trials (involving 10,806 women). Prophylactic oxytocin versus placebo Prophylactic oxytocin compared with placebo reduced the risk of PPH greater than 500 mL, (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.38 to 0.74; six trials, 4203 women; T² = 0.11, I² = 78%) and the need for therapeutic uterotonics (RR 0.56; 95% CI 0.36 to 0.87, four trials, 3174 women; T² = 0.10, I² = 58%). The benefit of prophylactic oxytocin to prevent PPH greater than 500 mL was seen in all subgroups. Decreased use of therapeutic uterotonics was only seen in the following subgroups: randomised trials with low risk of bias (RR 0.58; 95% CI 0.36 to 0.92; three trials, 3122 women; T² = 0.11, I² = 69%); trials that performed active management of the third stage (RR 0.39; 95% CI 0.26 to 0.58; one trial, 1901 women; heterogeneity not applicable); trials that delivered oxytocin as an IV bolus (RR 0.57; 95% CI 0.39 to 0.82; one trial, 1000 women

Prophylactic antibiotics in transurethral prostatectomy

DEFF Research Database (Denmark)

Qvist, N; Christiansen, H.M.; Ehlers, D

1984-01-01

The study included 88 patients with sterile urine prior to transurethral prostatectomy. Forty-five received a preoperative dose of 2 g of cefotaxime (Claforan) and the remaining 43 were given 10 ml of 0.9% NaCl. The two groups did not differ in frequency of postoperative urinary infection (greate...... of infection and the few side effects of the infections that did occur, prophylactic treatment with an antibiotic is not indicated for transurethral prostatectomy in patients with sterile urine....

Prophylactic pelvic drainage after rectal resection with extraperitoneal anastomosis: is it worthwhile? A meta-analysis of randomized controlled trials.

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Menahem, Benjamin; Vallois, Antoine; Alves, Arnaud; Lubrano, Jean

2017-11-01

The role of prophylactic pelvic drainage in reducing the postoperative complication rate after rectal surgery remains unclear and controversial. This review and meta-analysis of prospective randomized controlled trials was performed to determine whether drainage of the extraperitoneal anastomosis after rectal surgery impacts the postoperative complication rate. Study eligibility criteria included randomized controlled trials comparing prophylactic pelvic drainage after rectal surgery. The Medline and Cochrane Trials Register databases were searched for prospective randomized controlled trials comparing drainage versus no drainage after rectal surgery. Studies published until December 2016 were included. The meta-analysis was performed using Review Manager 5.0 (Cochrane Collaboration, Oxford, UK). Three randomized controlled trials involving 660 patients with extraperitoneal anastomosis after rectal surgery (330 with and 330 without prophylactic pelvic drains) were included. The overall mortality rate was 0.7% (2/267) in the drain group and 1.9% (5/261) in the no-drain group (P = 0.900). The anastomotic leakage rate was 14.8% (49/330) in the drain group and 16.7% (55/330) in the no-drain group (P = 0.370). The postoperative small bowel obstruction rate was significantly higher in the drain than no-drain group (50/267, 18.7% vs. 33/261, 12.6%; odds ratio, 1.61; 95% confidence interval, 1.00-2.60; P = 0.050). Prophylactic use of pelvic drainage after extraperitoneal colorectal anastomosis has no impact on the incidence of anastomotic leakage or postoperative death. However, it significantly increases the rate of postoperative small bowel obstruction.

Prophylactic role of melatonin against radiation induced damage in mouse cerebellum with special reference to Purkinje cells

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Sisodia, Rashmi; Kumari, Seema; Verma, Rajesh Kumar; Bhatia, A L [Neurobiology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302004 (India)

2006-06-15

Melatonin, a hormone with a proven antioxidative efficacy, crosses all morphophysiological barriers, including the blood-brain barrier, and distributes throughout the cell. The present study is an attempt to investigate the prophylactic influence of a chronic low level of melatonin against an acute radiation induced oxidative stress in the cerebellum of Swiss albino mice, with special reference to Purkinje cells. After 15 days of treatment the mice were sacrificed at various intervals from 1 to 30 days. Biochemical parameters included lipid peroxidation (LPO) and glutathione (GSH) levels as the endpoints. The quantitative study included alterations in number and volume of Purkinje cells. Swiss albino mice were orally administered a very low dose of melatonin (0.25 mg/mouse/day) for 15 consecutive days before single exposure to 4 Gy gamma radiation. Melatonin checked the augmented levels of LPO, by approximately 55%, by day 30 day post-exposure. Radiation induced depleted levels of GSH could be raised by 68.9% by day 30 post-exposure. Radiation exposure resulted in a reduction of the volume of Purkinje cells and their total number. The administration of melatonin significantly protected against the radiation induced decreases in Purkinje cell volume and number. Results indicate the antioxidative properties of melatonin resulting in its prophylactic property against radiation induced biochemical and cellular alterations in the cerebellum. The findings support the idea that melatonin may be used as an anti-irradiation drug due to its potent free radical scavenging and antioxidative efficacy.

[Cardiovascular effects produced by prophylactic digitalization during introduction of anaesthesia (author's transl)].

Science.gov (United States)

Köppen, R; Köhne, K; Busse, J; Hosselmann, I; Klaschik, E; Simons, F

1978-10-01

The narrow field of non-controversial indications concerning the application of digitalis glycosides is pointed out. Problems of routine digitalization of older patients not suffering from cardiac insuffiency are discussed with special regard to preparing them for operations. Up to now, from the viewpoint of anaesthesiologists no benefits of prophylactic digitalization have been found. In a retrospective computerized study, clinical hemodynamic parameters during introduction of anaesthesia have been investigated by means of anaesthetic data recorded during three years. Nondigitalized patients older than fifty years showed satisfactory cardiac functions, whereas prophylactically digitalized patients--compared with the control group--have been treated with plasma expanders earlier and at a double rate. Furthermore, higher heart frequencies and greater tendency to arrythmias were observed. Consequently, prophylactic digitalization cannot be recommended in general.

Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures

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Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Xia, Yang; Xu, Peng; Yao, Dezhong

2015-01-01

The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies. PMID:26496656

The current status of prophylactic replacement therapy in children and adults with haemophilia.

Science.gov (United States)

Ljung, Rolf; Gretenkort Andersson, Nadine

2015-06-01

Initiating prophylactic treatment at an early age is considered to be the optimal form of therapy for a child with haemophilia A or B. The pioneering long term experiences of prophylactic treatment from Sweden and The Netherlands demonstrated the benefit of prophylaxis in retrospective and observational studies. Decades later, these benefits were confirmed in a randomized controlled study in USA. We review the current status of prophylactic replacement therapy of haemophilia in children, adolescents, adults and the elderly. Prophylaxis should begin at an early age and there are arguments for continuing it into adulthood. The dose of prophylaxis is dependent on the goal of treatment, economic resources and venous access and should be tailored individually. Starting the first exposures to clotting factor concentrates as prophylactic treatment, instead of on-demand in response to a bleed, may decrease the frequency of inhibitors in patients with haemophilia A. Novel longer-acting products are being introduced that could be helpful for patients with difficult venous access and enable higher trough levels. © 2015 John Wiley & Sons Ltd.

Current status of prophylactic surgical treatment for familial adenomatous polyposis in Japan.

Science.gov (United States)

Yamadera, Masato; Ueno, Hideki; Kobayashi, Hirotoshi; Konishi, Tsuyoshi; Ishida, Fumio; Yamaguchi, Tatsuro; Hinoi, Takao; Inoue, Yasuhiro; Kanemitsu, Yukihide; Tomita, Naohiro; Ishida, Hideyuki; Sugihara, Kenichi

2017-06-01

We conducted this study to clarify the current clinical practice of prophylactic colectomy for patients with familial adenomatous polyposis (FAP) in Japan. This retrospective multi-center cohort study involved 23 specialized institutions for colorectal disease in Japan. We analyzed the records of 147 patients who underwent prophylactic surgical treatment between 2000 and 2012. Patients were divided into Group 1 (2000-2006) and Group 2 (2007-2012) based on their date of surgery. Age at the time of prophylactic surgery was 27 and 31 years in Groups 1 and 2, respectively. The proportion of attenuated FAP was significantly lower in Group 2 than in Group 1 (1.0 vs. 13 %, respectively). Pathological examination revealed an increased incidence of malignant polyps in the resected specimens from Group 2 patients (10 vs. 23 %, respectively; P = 0.034). Laparoscopic surgery was more frequent in Group 2 than in Group 1 (61 vs. 40 %, respectively). There was no surgical mortality in either group. Prophylactic surgery for FAP results in good short-term surgical outcomes in Japan. The current surgical approach is characterized by limited surgical indications for patients with attenuated FAP, delayed timing of colectomy, and the increasing standardization of laparoscopic surgery.

Is prophylactic fixation a cost-effective method to prevent a future contralateral fragility hip fracture?

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Faucett, Scott C; Genuario, James W; Tosteson, Anna N A; Koval, Kenneth J

2010-02-01

: A previous hip fracture more than doubles the risk of a contralateral hip fracture. Pharmacologic and environmental interventions to prevent hip fracture have documented poor compliance. The purpose of this study was to examine the cost-effectiveness of prophylactic fixation of the uninjured hip to prevent contralateral hip fracture. : A Markov state-transition model was used to evaluate the cost and quality-adjusted life-years (QALYs) for unilateral fixation of hip fracture alone (including internal fixation or arthroplasty) compared with unilateral fixation and contralateral prophylactic hip fixation performed at the time of hip fracture or unilateral fixation and bilateral hip pad protection. Prophylactic fixation involved placement of a cephalomedullary nail in the uninjured hip and was initially assumed to have a relative risk of a contralateral fracture of 1%. Health states included good health, surgery-related complications requiring a second operation (infection, osteonecrosis, nonunion, and malunion), fracture of the uninjured hip, and death. The primary outcome measure was the incremental cost-effectiveness ratio estimated as cost per QALY gained in 2006 US dollars with incremental cost-effectiveness ratios below $50,000 per QALY gained considered cost-effective. Sensitivity analyses evaluated the impact of patient age, annual mortality and complication rates, intervention effectiveness, utilities, and costs on the value of prophylactic fixation. : In the baseline analysis, in a 79-year-old woman, prophylactic fixation was not found to be cost-effective (incremental cost-effectiveness ratio = $142,795/QALY). However, prophylactic fixation was found to be a cost-effective method to prevent contralateral hip fracture in: 1) women 71 to 75 years old who had 30% greater relative risk for a contralateral fracture; and 2) women younger than age 70 years. Cost-effectiveness was greater when the additional costs of prophylaxis were less than $6000. However, for

The effect of prophylactic knee bracing on proprioception ...

African Journals Online (AJOL)

Enrique

S Davies (BA Hons, MA Ergonomics, PhD). Department of Human ... of joint position in space as sensed by the central nervous system.23. It incorporates joint .... The finding of this work supports the research hypothesis that prophylactic knee ...

A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers

Science.gov (United States)

2013-10-01

Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers Authors: DISTRIBUTION STATEMENT A. Paul C. Algra, LT, MC...May 2012 – May 2013 4. TITLE AND SUBTITLE A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers...SUPPLEMENTARY NOTES 14. ABSTRACT To prevent acute otitis externa (AOE) in the saturation setting and to decrease the side effects

Efficacy of prophylactic phototherapy for prevention of hyperbilirubinemia in very low birth weight newborns

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M. A. Mannan

2016-08-01

Full Text Available Background: Jaundice is a common clinical condition in newborn occurring in approximately 60% of term and 80% of preterm infants. Unconjugated hyperbilirubinemia is universally common in all preterm infants especially in newborns with very low biLth weight. Low birth weight and premature infants are at major risk for exaggerated hyperbilirubinemia that can lead to bilirubin encephalopathy. Significant heterogeneity in the approach to the treatment of jaundiced neonates exists throughout the world. Phototherapy is the most common treatment for neonatal hyperbilirubinemia and could be most effective in preventing the sequelae of hyperbilirubinemia if initiated prophylactically. This randomized clinical trial has been proposed with the objective of assessing the efficacy of prophylactic photo therapy in preventing significant rise of unconjugated hyperbilirubinemia in premature neonates weighing less than 1500 gram and therefore to decrease the need for exchange transfusion and finally to reduce hospital stay due to hyperbilirubinemia. Methods: This randomized controlled clinical trial enrolled sixty newborns with birth weight less than 1500 gram. They were divided into two groups: 1 Prophylactic group, in whom phototherapy was started within 24 hours of birth and continued for 7 days and 2 Control group in whom therapeutic phototherapy was started considering serum bilirubin level and other clinical condi­tions as per institutional guidelines. Mean value of total serum bilirubin (TSB, duration of phototherapy, the need for exchange transfusion and duration of hospital stay in both groups were analyzed.Results: The maximum mean TSB level in prophylactic group was observed on 7th day and in control group it was observed on 3rd day of life. The total serum bilirubin levels were significantly lower in the 3rd and 5th days of life in the prophylactic group in comparison to control group (P value 0.001. Total serum bilirubin level exceeded therapeutic

HIF-1α pathway: role, regulation and intervention for cancer therapy

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Georgina N. Masoud

2015-09-01

Full Text Available Hypoxia-inducible factor-1 (HIF-1 has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O2 levels is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.

Prophylactic treatment of migraine in children. Part 1. A systematic review of non-pharmacological trials

NARCIS (Netherlands)

Damen, L; Bruijn, J; Koes, BW; Berger, MY; Passchier, J; Verhagen, AP

The aim of this study was to assess the efficacy of non-pharmacological prophylactic treatments of migraine in children. Databases were searched from inception to June 2004 and references were checked. We selected controlled trials reporting the effects of non-pharmacological prophylactic treatments

Patient and parent preferences for characteristics of prophylactic treatment in hemophilia

Directory of Open Access Journals (Sweden)

Furlan R

2015-11-01

Full Text Available Roberto Furlan,1 Sangeeta Krishnan,2 Jeffrey Vietri3 1Advanced Methods, Kantar Health, Epsom, Surrey, UK; 2Global Health Economics and Outcomes Research, Biogen, MA, USA; 3Health Outcomes, Kantar Health, Milan, Italy Introduction: New longer-acting factor products will potentially allow for less frequent infusion in prophylactic treatment of hemophilia. However, the role of administration frequency relative to other treatment attributes in determining preferences for prophylactic hemophilia treatment regimens is not well understood. Aim: To identify the relative importance of frequency of administration, efficacy, and other treatment characteristics among candidates for prophylactic treatment for hemophilia A and B. Method: An Internet survey was conducted among hemophilia patients and the parents of pediatric hemophilia patients in Australia, Canada, and the US. A monadic conjoint task was included in the survey, which varied frequency of administration (three, two, or one time per week for hemophilia A; twice weekly, weekly, or biweekly for hemophilia B, efficacy (no bleeding or breakthrough bleeding once every 4 months, 6 months, or 12 months, diluent volume (3 mL vs 2.5 mL for hemophilia A; 5 mL vs 3 mL for hemophilia B, vials per infusion (2 vs 1, reconstitution device (assembly required vs not, and manufacturer (established in hemophilia vs not. Respondents were asked their likelihood to switch from their current regimen to the presented treatment. Respondents were told to assume that other aspects of treatment, such as risk of inhibitor development, cost, and method of distribution, would remain the same. Results: A total of 89 patients and/or parents of children with hemophilia A participated; another 32 were included in the exercise for hemophilia B. Relative importance was 47%, 24%, and 18% for frequency of administration, efficacy, and manufacturer, respectively, in hemophilia A; analogous values were 48%, 26%, and 21% in

The role of APC in WNT pathway activation in serrated neoplasia.

Science.gov (United States)

Borowsky, Jennifer; Dumenil, Troy; Bettington, Mark; Pearson, Sally-Ann; Bond, Catherine; Fennell, Lochlan; Liu, Cheng; McKeone, Diane; Rosty, Christophe; Brown, Ian; Walker, Neal; Leggett, Barbara; Whitehall, Vicki

2018-03-01

Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively. WNT pathway activation was seen to a lesser extent in serrated pathway lesions. It occurred at the transition to dysplasia in serrated polyps with a significant increase in nuclear β-catenin labeling from sessile serrated adenomas (10%) to sessile serrated adenomas with dysplasia (55%) and traditional serrated adenomas (9%) to traditional serrated adenomas with dysplasia (39%) (P=0.0001). However, unlike the conventional pathway, truncating APC mutations were rare in the serrated pathway lesions especially sessile serrated adenomas even when dysplastic (15%) and in the BRAF mutant cancers with microsatellite instability that arise from them (8%). In contrast, APC missense mutations that were rare in conventional pathway adenomas and cancers (3% in BRAF wild-type cancers) were more frequent in BRAF mutant cancers with microsatellite instability (32%). We conclude that increased WNT signaling is important in the transition to malignancy in the serrated pathway but that APC mutation is less common and the spectrum of mutations is different than in conventional colorectal carcinogenesis. Moderate impact APC mutations and non-APC-related causes of increased WNT signaling may have a more important role in serrated neoplasia than the truncating APC mutations

Prophylactic and therapeutic effect of Punica granatum in trinitrobenzene sulfonic acid induced inflammation in rats.

Science.gov (United States)

Riaz, Azra; Khan, Rafeeq Alam; Afroz, Syeda; Mallick, Neelam

2017-01-01

Pomegranate (Punica granatum L., Punicaceae) contains varieties of antioxidants and phytochemicals; there are evidences that phytochemicals and antioxidants play a vital role in reducing inflammation. Hence this investigation was planned to assess the outcome of Punica granatum on trinitrobenzene sulfonic acid provoked colitis in rats at 2, 5 and 8ml/kg of the body weight. The effect of P. granatum was assessed in two group i.e. prophylaxis as pre-colitis and therapeutic as post-colitis. After completion of dosing in both the groups, macroscopic and histological examination of colon was carried out along with estimation of serum myeloperoxidase, glutathione, alkaline phosphate, fibrinogen and C-reactive protein. In prophylactic procedure P. granatum revealed significant (Pgranatum have a role in prevention as well as treatment of inflammation.

Chemical composition and prophylactic effects of Saturja ...

African Journals Online (AJOL)

Results: The main components of SKEO were carvacrol (78.8%), thymol (7.5%), and beta-Bisabolene (1.2%). Findings of prophylactic effects revealed that mortality rate of infected mice was 8 days after oral administration of SKEO at the concentration of 0.2 and 0.3ml/kg (P<0.05). In contrast, this value for control group was ...

Prophylactic antibiotic for pacemaker surgery: what is optimal ...

African Journals Online (AJOL)

One of them, a bed-ridden patient developed severe pocket infection necessitating explantation and replacement 3 weeks later. Conclusions: We noted with satisfaction that short regime of prophylactic parentral ceftriaxone is effective in preventing pacemaker infection and there is no need for the long regimen. Niger Med J.

The effect of colloid preload versus prophylactic ephedrine ...

African Journals Online (AJOL)

Aim: We aimed to investigate the effect of colloid infusion immediately before the spinal anesthesia, and the prophylactic intravenous (IV) infusion of ephedrine after injection of intrathecal bupivacaine on hemodynamic parameters, QT, The QT interval corrected for heart rate (QTc), and dispersion of QTc (QTcDisp) intervals ...

The effect of prophylactic lymphovenous anastomosis and shunts for preventing cancer-related lymphedema

DEFF Research Database (Denmark)

Jørgensen, Mads G; Toyserkani, Navid M; Sørensen, Jens A

2018-01-01

BACKGROUND: Lymphedema is one of the most dreaded side effects to any cancer treatment involving lymphadenectomy. Progressed lymphedema is adversely complex and currently there is no widely acknowledged curative treatment. Therefore recent focus has shifted to risk reduction and prevention. It has...... with prophylactic LVA had a significant reduction in lymphedema incidence (Relative risk: 0.33, 95%CI: 0.19 to 0.56) when compared to patients receiving no prophylactic treatment (P 

The effect of prophylactic antipyretic administration on post-vaccination adverse reactions and antibody response in children: a systematic review.

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Rashmi Ranjan Das

Full Text Available Prophylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children.A systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. Randomized controlled trials (RCTs comparing prophylactic antipyretic treatment versus placebo post-vaccination in children ≤ 6 years of age were included. Two reviewers independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data [PROSPERO registration: CRD42014009717].Of 2579 citations retrieved, a total of 13 RCTs including 5077 children were included in the review. Prophylactic antipyretic administration significantly reduced the febrile reactions (≥ 38.0 °C after primary and booster vaccinations. Though there were statistically significant differences in the antibody responses between the two groups, the prophylactic PCM group had what would be considered protective levels of antibodies to all of the antigens given after the primary and booster vaccinations. No significant difference in the nasopharyngeal carriage rates (short-term and long-term of H. influenzae or S. pneumoniae serotypes was found between the prophylactic and no prophylactic PCM group. There was a significant reduction in the local and systemic symptoms after primary, but not booster vaccinations.Though prophylactic antipyretic administration leads to relief of the local and systemic symptoms after primary vaccinations, there is a reduction in antibody responses to some vaccine antigens without any effect on the nasopharyngeal carriage rates of S. pneumoniae & H. influenza serotypes. Future trials and surveillance programs should also aim at

Application of radiotracers in the assessment of prophylactic role of zinc in experimental model of colon carcinogenesis

International Nuclear Information System (INIS)

Dani, Vijayata; Vaiphei, K.; Dhawan, D.K.

2010-01-01

Full text: The present study elucidated the modulatory effects of zinc in 1,2 dimethylhydrazine (DMH) induced colon carcinogenesis using radiotracer techniques. Rats were segregated into four groups viz., untreated control, DMH treated, zinc treated, DMH+zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/Kg body weight) for 16 weeks. Zinc was supplemented to rats at a dose level of 227mg/L in drinking water, ad libitum. The prophylactic role of zinc was assessed by following radiotracer techniques viz: whole body biological half life of 65 Zn and 65 Zn biodistribution, subcellular distribution, uptake of 3 H-Thymidine to assess rate of DNA synthesis, radiorespirometric determination of 14 C-D-Glucose metabolism and in-vitro uptake of labeled aminoacids. The statistical significance of the data has been determined by using one way analysis of variance (ANOVA) followed by multiple post - hoc test. The carcinogenic state in the animals was confirmed by histopathological examination, whereby, well-differentiated signs of dysplasia were evident in colonic tissue sections of DMH treated rats. The biokinetics study of zinc revealed a significant decrease in the biological half life of 65 Zn. Also, DMH treatment caused a significant increase in the percent uptake values of 65 Zn in the colon, small intestine, kidney and blood, whereas a significant decrease was observed in the liver. The uptake rates of amino acids viz: 14 C-glycine, 14 C-alanine and 14 C-lysine were significantly higher in the DMH treated colons. Moreover, a significant increase in the uptake and turnover of 14 C-D-Glucose was also observed after DMH treatment. A significant increase in the ( 3 H)-thymidine uptake was observed following 16 weeks DMH treatment. However, supplementation of zinc significantly reversed the proliferative effect of DMH as evidenced by ameliorating the altered parameters. Radiotracer techniques play an important role in assessing

Prophylactic procedures in women with gene mutations BRCA1 and BRCA2

International Nuclear Information System (INIS)

Bella, V.

2012-01-01

Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence, it occurs in the familial or hereditary form. Genetic testing for mutation BRCA1 and BRCA2 helps to identify women, who are at increased risk of developing breast and ovarian cancer. Women with the hereditary form of breast cancer occurs in 5 -10%. Women with mutations BRCA1 and BRCA2 have to be classified to intensive dispensaration, and may consider several options for breast cancer prevention, as prophylactic mastectomy, prophylactic salpingo-oophorectomy or chemo prevention. (author)

Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation.

Science.gov (United States)

Zhang, Ji-Chun; Yao, Wei; Dong, Chao; Yang, Chun; Ren, Qian; Ma, Min; Han, Mei; Wu, Jin; Ushida, Yusuke; Suganuma, Hiroyuki; Hashimoto, Kenji

2017-01-01

Inflammation plays a role in the pathophysiology of depression. Sulforaphane (SFN), an isothiocyanate compound derived from broccoli, is a potent activator of the NF-E2-related factor-2 (Nrf2), which plays a role in inflammation. In this study, we examined whether the prevention effects of SFN in lipopolysaccharide (LPS) induced depression-like behavior in mice. Pretreatment with SFN significantly blocked an increase in the serum tumor necrosis factor-α (TNF-α) level and an increase in microglial activation of brain regions after a single administration of LPS (0.5 mg/kg). Furthermore, SFN significantly potentiated increased serum levels of IL-10 after LPS administration. In the tail-suspension test and forced swimming test, SFN significantly attenuated an increase of the immobility time after LPS administration. In addition, SFN significantly recovered to control levels for LPS-induced alterations in the proteins such as brain-derived neurotrophic factor, postsynaptic density protein 95 and AMPA receptor 1 (GluA1) and dendritic spine density in the brain regions. Finally, dietary intake of 0.1% glucoraphanin (a glucosinolate precursor of SFN) food during the juvenile and adolescence could prevent the onset of LPS-induced depression-like behaviors and dendritic spine changes in the brain regions at adulthood. In conclusion, these findings suggest that dietary intake of SFN-rich broccoli sprout has prophylactic effects on inflammation-related depressive symptoms. Therefore, supplementation of SFN-rich broccoli sprout could be prophylactic vegetable to prevent or minimize the relapse by inflammation in the remission state of depressed patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Heme and Heme-Proteins in Trypanosomatid Essential Metabolic Pathways

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Karina E. J. Tripodi

2011-01-01

Full Text Available Around the world, trypanosomatids are known for being etiological agents of several highly disabling and often fatal diseases like Chagas disease (Trypanosoma cruzi, leishmaniasis (Leishmania spp., and African trypanosomiasis (Trypanosoma brucei. Throughout their life cycle, they must cope with diverse environmental conditions, and the mechanisms involved in these processes are crucial for their survival. In this review, we describe the role of heme in several essential metabolic pathways of these protozoans. Notwithstanding trypanosomatids lack of the complete heme biosynthetic pathway, we focus our discussion in the metabolic role played for important heme-proteins, like cytochromes. Although several genes for different types of cytochromes, involved in mitochondrial respiration, polyunsaturated fatty acid metabolism, and sterol biosynthesis, are annotated at the Tritryp Genome Project, the encoded proteins have not yet been deeply studied. We pointed our attention into relevant aspects of these protein functions that are amenable to be considered for rational design of trypanocidal agents.

Iranian women's attitude toward prophylactic mastectomy for breast cancer

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Keivan Majidzadeh-A

2016-01-01

Conclusion: Preventive mastectomy has a higher rate of acceptability among women who have had a family history of breast cancer. Therefore, it may be concluded that raising public awareness about the advantages of prophylactic mastectomy could help better address breast cancer in Iran.

Decision-making process of women carrying a BRCA1 or BRCA2 mutation who have chosen prophylactic mastectomy.

Science.gov (United States)

McQuirter, Megan; Castiglia, Luisa Luciani; Loiselle, Carmen G; Wong, Nora

2010-05-01

To explore the decision-making process of women with a BRCA1 or BRCA2 gene mutation who have chosen to undergo prophylactic mastectomy. Cross-sectional, qualitative, descriptive design. Participants were recruited from an outpatient cancer prevention center in the oncology and medical genetics departments of a large university-affiliated hospital in Montreal, Quebec, Canada. 10 women carrying a BRCA1 or BRCA2 mutation; 8 previously had had a prophylactic mastectomy and 2 were scheduled for surgery at the time of study. Semistructured, in-depth interviews were conducted. Field notes were written and audiotapes were transcribed verbatim. The textual data were coded and analyzed. Decision-making process for prophylactic mastectomy. Two broad findings emerged. First, several intrapersonal and contextual factors interacted throughout the process to move women either closer to choosing a prophylactic mastectomy or further from the decision. Second, all women reported experiencing a "pivotal point," an emotionally charged event when the decision to have a prophylactic mastectomy became definitive. Pivotal points for patients included either receiving a positive result for a genetic mutation or a breast cancer diagnosis for herself or a family member in the context of positive mutation status. Decision making about prophylactic mastectomy was an affective and intuitive process incorporating contexts and their relations rather than a rational, straight-forward process of weighing pros and cons. Supportive interventions for women in this population should explicitly address the individual and the inter-relationships of contextual factors that shape decision making about prophylactic mastectomy while recognizing important affective components involved.

Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

Science.gov (United States)

Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

2016-01-01

Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

Efficacy of prophylactic uterine artery embolization before obstetrical procedures with high risk for massive bleeding

International Nuclear Information System (INIS)

Ko, Heung Kyu; Shin, Ji Hoon; Ko, Gi Young; Gwon, Dong Il; Kim, Jin Hyung; Han, Ki Chang; Lee, Shin Wha

2017-01-01

To evaluate the safety and efficacy of prophylactic uterine artery embolization (UAE) before obstetrical procedures with high risk for massive bleeding. A retrospective review of 29 female patients who underwent prophylactic UAE from June 2009 to February 2014 was performed. Indications for prophylactic UAE were as follows: dilatation and curettage (D and C) associated with ectopic pregnancy (cesarean scar pregnancy, n = 9; cervical pregnancy, n = 6), termination of pregnancy with abnormal placentation (placenta previa, n = 8), D and C for retained placenta with vascularity (n = 5), and D and C for suspected gestational trophoblastic disease (n = 1). Their medical records were reviewed to evaluate the safety and efficacy of UAE. All women received successful bilateral prophylactic UAE followed by D and C with preservation of the uterus. In all patients, UAE followed by obstetrical procedure prevented significant vaginal bleeding on gynecologic examination. There was no major complication related to UAE. Vaginal spotting continued for 3 months in three cases. Although oligomenorrhea continued for six months in one patient, normal menstruation resumed in all patients afterwards. During follow-up, four had subsequent successful natural pregnancies. Spontaneous abortion occurred in one of them during the first trimester. Prophylactic UAE before an obstetrical procedure in patients with high risk of bleeding or symptomatic bleeding may be a safe and effective way to manage or prevent serious bleeding, especially for women who wish to preserve their fertility

Efficacy of prophylactic uterine artery embolization before obstetrical procedures with high risk for massive bleeding

Energy Technology Data Exchange (ETDEWEB)

Ko, Heung Kyu; Shin, Ji Hoon; Ko, Gi Young; Gwon, Dong Il; Kim, Jin Hyung; Han, Ki Chang; Lee, Shin Wha [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

2017-04-15

To evaluate the safety and efficacy of prophylactic uterine artery embolization (UAE) before obstetrical procedures with high risk for massive bleeding. A retrospective review of 29 female patients who underwent prophylactic UAE from June 2009 to February 2014 was performed. Indications for prophylactic UAE were as follows: dilatation and curettage (D and C) associated with ectopic pregnancy (cesarean scar pregnancy, n = 9; cervical pregnancy, n = 6), termination of pregnancy with abnormal placentation (placenta previa, n = 8), D and C for retained placenta with vascularity (n = 5), and D and C for suspected gestational trophoblastic disease (n = 1). Their medical records were reviewed to evaluate the safety and efficacy of UAE. All women received successful bilateral prophylactic UAE followed by D and C with preservation of the uterus. In all patients, UAE followed by obstetrical procedure prevented significant vaginal bleeding on gynecologic examination. There was no major complication related to UAE. Vaginal spotting continued for 3 months in three cases. Although oligomenorrhea continued for six months in one patient, normal menstruation resumed in all patients afterwards. During follow-up, four had subsequent successful natural pregnancies. Spontaneous abortion occurred in one of them during the first trimester. Prophylactic UAE before an obstetrical procedure in patients with high risk of bleeding or symptomatic bleeding may be a safe and effective way to manage or prevent serious bleeding, especially for women who wish to preserve their fertility.

Cancer registries and monitoring the impact of prophylactic human papillomavirus vaccines: the potential role.

Science.gov (United States)

Saraiya, Mona; Goodman, Marc T; Datta, S Deblina; Chen, Vivien W; Wingo, Phyllis A

2008-11-15

The recent US Food and Drug Administration licensure of a prophylactic vaccine against oncogenic human papillomavirus (HPV) types 16 and 18, the first of its kind, poses unique challenges in postmarketing vaccine surveillance, especially in measuring vaccine effectiveness against biologic endpoints of HPV infection. Historically, the national system of population-based cancer registries in the US has provided high-quality data on cancer incidence and mortality for the most important biologic endpoints, namely, anogenital cancers and some oral cavity/oropharyngeal cancers. There also has been some data collection on cancer precursors; however, this activity has been inconsistent and of lower priority. Because effectiveness against HPV-associated cancers will not be measurable for several decades, strengthening and possibly expanding the capacity of registries to collect precancer data, which are earlier manifestations of infection, must be considered. Collecting type-specific data on HPV-associated precancers and cancers. While keeping in mind the current limitations of registry operations, they discuss resources that may be needed to implement and sustain these types of activities.

Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases

Science.gov (United States)

Shi, Juan; Chi, Shuhong; Xue, Jing; Yang, Jiali; Li, Feng; Liu, Xiaoming

2016-01-01

The Wnt signaling pathway plays a key role in many biological aspects, such as cellular proliferation, tissue regeneration, embryonic development, and other systemic effects. Under a physiological condition, it is tightly controlled at different layers and arrays, and a dysregulated activation of this signaling has been implicated into the pathogenesis of various human disorders, including autoimmune diseases. Despite the fact that therapeutic interventions are available for ameliorating disease manifestations, there is no curative therapy currently available for autoimmune disorders. Increasing lines of evidence have suggested a crucial role of Wnt signaling during the pathogenesis of many autoimmune diseases; in addition, some of microRNAs (miRNAs), a class of small, noncoding RNA molecules capable of transcriptionally regulating gene expression, have also recently been demonstrated to possess both physiological and pathological roles in autoimmune diseases by regulating the Wnt signaling pathway. This review summarizes currently our understanding of the pathogenic roles of Wnt signaling in several major autoimmune disorders and miRNAs, those targeting Wnt signaling in autoimmune diseases, with a focus on the implication of the Wnt signaling as potential biomarkers and therapeutic targets in immune diseases, as well as miRNA-mediated regulation of Wnt signaling activation in the development of autoimmune diseases. PMID:27110577

Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases

Directory of Open Access Journals (Sweden)

Juan Shi

2016-01-01

Full Text Available The Wnt signaling pathway plays a key role in many biological aspects, such as cellular proliferation, tissue regeneration, embryonic development, and other systemic effects. Under a physiological condition, it is tightly controlled at different layers and arrays, and a dysregulated activation of this signaling has been implicated into the pathogenesis of various human disorders, including autoimmune diseases. Despite the fact that therapeutic interventions are available for ameliorating disease manifestations, there is no curative therapy currently available for autoimmune disorders. Increasing lines of evidence have suggested a crucial role of Wnt signaling during the pathogenesis of many autoimmune diseases; in addition, some of microRNAs (miRNAs, a class of small, noncoding RNA molecules capable of transcriptionally regulating gene expression, have also recently been demonstrated to possess both physiological and pathological roles in autoimmune diseases by regulating the Wnt signaling pathway. This review summarizes currently our understanding of the pathogenic roles of Wnt signaling in several major autoimmune disorders and miRNAs, those targeting Wnt signaling in autoimmune diseases, with a focus on the implication of the Wnt signaling as potential biomarkers and therapeutic targets in immune diseases, as well as miRNA-mediated regulation of Wnt signaling activation in the development of autoimmune diseases.

Prophylactic belladonna suppositories on anesthetic recovery after robotic assisted laparoscopic prostatectomy.

Science.gov (United States)

Scavonetto, Federica; Lamborn, David R; McCaffrey, Joan M; Schroeder, Darrell R; Gettman, Mattew T; Sprung, Juraj; Weingarten, Toby N

2013-06-01

Two prospective trials have demonstrated prophylactic antimuscarinics following prostatectomy reduce pain from bladder spasms. Our practice adopted the routine administration of prophylactic belladonna and opium (B&O) suppositories to patients undergoing robotic assisted laparoscopic radical prostatectomy (RALP). The aim of this study is to determine if this change in clinical practice was associated with improvement of postoperative outcomes. The medical records of 202 patients that underwent RALP surgery who were or were not administered prophylactic B&O suppositories in the immediate postoperative period were abstracted for duration of anesthesia recovery, pain and analgesic use. Patient and surgical characteristics between groups were similar except B&O group were slightly older (p = 0.04) and administered less opioid analgesics (p = 0.05). There was no difference between groups in the duration of phase I recovery from anesthesia (p = 0.96). Multivariable adjustments for age, body mass index, American Society of Anesthesiologists physical status, and surgical duration were made, and again it was found that suppository administration had no association with phase I recovery times (p = 0.94). The use of antimuscarinic medication for bladder spams in the B&O group was less during phase I recovery (p suppositories at the immediate conclusion of RALP surgery was not associated with improvements of the postoperative course.

Prophylactic Oophorectomy: Preventing Cancer by Surgically Removing Your Ovaries

Science.gov (United States)

... much lower than the lifetime risk of ovarian cancer if the ovaries remain intact. Prophylactic oophorectomy might relieve much of ... cancer. Screening usually includes a blood test for cancer antigen (CA) 125 and an ultrasound exam of your ovaries. In theory, increased screening should be able to ...

The effect of Prophylactic knee bracing on selected performance ...

African Journals Online (AJOL)

The objective of this study was to determine if the wearing of a prophylactic knee brace by uninjured rugby players affected the following performance based parameters: speed, agility, strength, proprioception and economy of running. Thirty rugby players were subjected to a selected number of carefully monitored ...

Prescribing prophylactic antibiotics to users of therapeutic contact lenses.

Science.gov (United States)

Colomé-Campos, J; Quevedo-Junyent, L; Godoy-Barreda, N; Martínez-Salcedo, I; Romero-Aroca, P

2013-03-01

To describe the benefits and optimum use of prophylactic antibiotics in users of therapeutic contact lenses (TCL). A microbiological study was carried out on samples from 33 patients who continuously wore TCL. The resistance to antibiotics of bacteria isolated in our health region was also reviewed. An assessment was also made on whether there were microorganisms of a higher pathogenic potential in TCL than conventional contact lenses, as reported in the literature. No bacteria were isolated from 17 (52%) of the 33 lenses studied. From the 16 (48%) remaining lenses, coagulase negative Staphylococci were isolated from 10 (62%), Propionibacterium acnes from 4 (25%), and Corynebacterium from 2 (13%). The high number of negative cultures and the presence of saprophytic bacteria indicate that prophylactic antibiotic treatment is not precise. The most frequent pathogenic bacteria found in contact lenses are strongly resistant to the current commercially available antibiotics. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Efficacy of prophylactic irradiation in altering renal allograft survival

International Nuclear Information System (INIS)

Faber, R.; Johnson, H.K.; Braren, H.V.; Richie, R.E.

1974-01-01

Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids

Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy

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Lee, Taewoo; Biddle, Andrea K.; Lionaki, Sofia; Derebail, Vimal K.; Barbour, Sean J.; Tannous, Sameer; Hladunewich, Michelle A.; Hu, Yichun; Poulton, Caroline J.; Mahoney, Shannon L.; Jennette, J. Charles; Hogan, Susan L.; Falk, Ronald J.; Cattran, Daniel C.; Reich, Heather N.; Nachman, Patrick H.

2014-01-01

Primary membranous nephropathy is associated with increased risk of venous thromboembolic events, which are inversely correlated with serum albumin levels. To evaluate the potential benefit of prophylactic anticoagulation (venous thromboembolic events prevented) relative to the risk (major bleeds), we constructed a Markov decision model. The venous thromboembolic event risk according to serum albumin was obtained from an inception cohort of 898 patients with primary membranous nephropathy. Risk estimates of hemorrhage were obtained from a systematic literature review. Benefit-to-risk ratios were predicted according to bleeding risk and serum albumin. This ratio increased with worsening hypoalbuminemia from 4.5:1 for an albumin under 3 g/dl to 13.1:1 for an albumin under 2 g/dl in patients at low bleeding risk. Patients at intermediate bleeding risk with an albumin under 2 g/dl have a moderately favorable benefit-to-risk ratio (under 5:1). Patients at high bleeding risk are unlikely to benefit from prophylactic anticoagulation regardless of albuminemia. Probabilistic sensitivity analysis, to account for uncertainty in risk estimates, confirmed these trends. From these data, we constructed a tool to estimate the likelihood of benefit based on an individual’s bleeding risk profile, serum albumin level, and acceptable benefit-to-risk ratio (http://www.gntools.com). This tool provides an approach to the decision of prophylactic anticoagulation personalized to the individual’s needs and adaptable to dynamic changes in health status and risk profile. PMID:24336031

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

2005-01-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo [National Hospital Organization Osaka Minami Medical Center, Kawachinagano (Japan)

2005-03-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic teeth.

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Pickenpaugh, L; Reader, A; Beck, M; Meyers, W J; Peterson, L J

2001-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of prophylactic amoxicillin on the occurrence of endodontic flare-up in asymptomatic, necrotic teeth. Seventy patients participated and had a clinical diagnosis of an asymptomatic, necrotic tooth with associated periapical radiolucency. One hour before endodontic treatment, patients randomly received either 3 g of amoxicillin or 3 g of a placebo control in a double-blind manner. After endodontic treatment, each patient received: ibuprofen; acetaminophen with codeine (30 mg); and a 5 1/2-day diary to record pain, swelling, percussion pain, and number and type of pain medication taken. The results demonstrated 10% of the 70 patients had a flare-up characterized by moderate-to-severe postoperative pain or swelling that began approximately 30 h after endodontic treatment and persisted for an average of 74 h. Of the seven patients who had flare-ups, 4 were in the amoxicillin group and 3 were not. Prophylactic amoxicillin did not significantly (p = 0.80) influence the endodontic flare-up. We concluded that a prophylactic dose of amoxicillin before endodontic treatment of asymptomatic, necrotic teeth had no effect on the endodontic flare-up.

Role of the Mixed-Lineage Protein Kinase Pathway in the Metabolic Stress Response to Obesity

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Shashi Kant

2013-08-01

Full Text Available Saturated free fatty acid (FFA is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK pathway that activates cJun NH2-terminal kinase (JNK. Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to the metabolic effects of MLK deficiency. These data confirm that the MLK pathway plays a critical role in the metabolic response to obesity.

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

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Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

2016-10-01

Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

Prophylactic antibiotics in vesicoureteric reflux: Evidence-based analysis

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M S Ansari

2009-01-01

Full Text Available Objectives: The aim of this review was to systematically examine the available evidence for the effectiveness of prophylactic antibiotics in cases of vesicoureteric reflux (VUR. Materials and Methods: We searched the relevant data on medical management of VUR and the date of last search was June 2008. The search included both randomized controlled trials as well as the nonrandomized trials and the data sources were; MEDLINE, online peer reviewed journals, Cochrane database and abstracts from conference proceedings. Results: Barring few most of the studies published on medical management were nonrandomized. Besides being small in number many of these studies were of poor-quality and poorly designed eventually failing in giving a reliable answer in this regard. Few of the studies suggest that the children with low grade VUR might do well even without antibiotic prophylaxis. Conclusions : In the absence of properly designed, randomized controlled trials and long-term follow-up the question of antibiotic prophylaxis in cases of VUR remains unanswered in large part of it. Whether to give prophylactic antibiotics or not would ultimately need a shared decision-making involving both the treating physician and the parents assessing both the risks and the benefits.

Classification of prophylactic antiradiation drugs as the consistency of conceptual basis of current radiation pharmacology

International Nuclear Information System (INIS)

Vasin, M.F

1999-01-01

The consistency of the classification of prophylactic antiradiation drugs have been given consideration as history of their discovery, theory of the radioprotection mechanisms and their use in applied medicine. Prophylactic drugs consists of radioprotectors with short-term of long-term action, drugs stimulating radioresistance, the ones suppressing symptoms of primary radiation reaction, the ones of early detoxication, the ones for adsorption and elimination of radionuclides from an organism [ru

Membrane trafficking pathways and their roles in plant-microbe interactions.

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Inada, Noriko; Ueda, Takashi

2014-04-01

Membrane trafficking functions in the delivery of proteins that are newly synthesized in the endoplasmic reticulum (ER) to their final destinations, such as the plasma membrane (PM) and the vacuole, and in the internalization of extracellular components or PM-associated proteins for recycling or degradative regulation. These trafficking pathways play pivotal roles in the rapid responses to environmental stimuli such as challenges by microorganisms. In this review, we provide an overview of the current knowledge of plant membrane trafficking and its roles in plant-microbe interactions. Although there is little information regarding the mechanism of pathogenic modulation of plant membrane trafficking thus far, recent research has identified many membrane trafficking factors as possible targets of microbial modulation.

Prophylactic antibiotics in pediatric shunt surgery.

Science.gov (United States)

Biyani, N; Grisaru-Soen, G; Steinbok, P; Sgouros, S; Constantini, S

2006-11-01

The optimal antibiotic prophylaxis for pediatric shunt-related procedures is not clear. There is much inconsistency among different medical centers. This paper summarizes and analyzes the various prophylactic antibiotic regiments used for shunt-related surgeries at different pediatric neurosurgery centers in the world. A survey questionnaire was distributed through the Pediatric Neurosurgery list-server (an e-mail-based special interest group in pediatric neurosurgery). Forty-five completed questionnaires were received, one per medical center, primarily from pediatric neurosurgeons with the following geographic breakdown: 25 from North America, 13 from Europe, and 7 from Asia and other countries. All centers routinely administered prophylactic antibiotics for shunt-related procedures. The drugs of choice were first-generation cephalosporins (23), second-generation cephalosporins (10), naficillin/oxacillin (4), vancomycin (3), clindamycin (1), amoxicillin (1), and mixed protocols in three centers. The initial drug administration ("first dose") was: in the department before transfer to operating room (5), upon arrival to operating room (11), at induction of anesthesia (13), and at initial skin incision (16). The duration of antibiotic dosage also varied: single dose (13), 24-h administration (26), 48-h administration (2), and longer than 48 h in four centers. Two general tendencies were noted, common to the majority of participating centers. There was a general trend to modify antibiotic treatment protocol in "high-risk" populations. The second common theme noted in more than half of responding centers was the use of long-term antibiotic treatment for externalized devices (such as externalized shunts, external ventricular drains or lumbar drains), usually till the device was in place.

Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

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Herath, Samantha C; Poole, Phillippa

2013-11-28

There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). To determine whether or not regular treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was August 2013. Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. We used the standard methods of The Cochrane Collaboration. Data were extracted and analysed by two independent review authors. Seven RCTs involving 3170 patients were included in this systematic review. All studies were published between 2001 and 2011. Five studies were of continuous antibiotics and two studies were of intermittent antibiotic prophylaxis (termed 'pulsed' for this review). The antibiotics investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin. Azithromycin, erythromycin and clarithromycin are macrolides while moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the results were of moderate quality. The risk of bias of the included studies was generally low, and we did not downgrade the quality of evidence for risk of bias.The trials recruited participants with a mean age of 66 years and with at least a moderate severity of COPD. Three trials included participants with frequent exacerbations and two trials recruited participants requiring systemic steroids or antibiotics, or both, or who were at the end stage of their disease and required oxygen.The primary outcomes for this review were the number of exacerbations and quality of life.With use of continuous prophylactic antibiotics the number of patients experiencing

The role of the Hedgehog signaling pathway in cancer: A comprehensive review

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Ana Marija Skoda

2018-02-01

Full Text Available The Hedgehog (Hh signaling pathway was first identified in the common fruit fly. It is a highly conserved evolutionary pathway of signal transmission from the cell membrane to the nucleus. The Hh signaling pathway plays an important role in the embryonic development. It exerts its biological effects through a signaling cascade that culminates in a change of balance between activator and repressor forms of glioma-associated oncogene (Gli transcription factors. The components of the Hh signaling pathway involved in the signaling transfer to the Gli transcription factors include Hedgehog ligands (Sonic Hh [SHh], Indian Hh [IHh], and Desert Hh [DHh], Patched receptor (Ptch1, Ptch2, Smoothened receptor (Smo, Suppressor of fused homolog (Sufu, kinesin protein Kif7, protein kinase A (PKA, and cyclic adenosine monophosphate (cAMP. The activator form of Gli travels to the nucleus and stimulates the transcription of the target genes by binding to their promoters. The main target genes of the Hh signaling pathway are PTCH1, PTCH2, and GLI1. Deregulation of the Hh signaling pathway is associated with developmental anomalies and cancer, including Gorlin syndrome, and sporadic cancers, such as basal cell carcinoma, medulloblastoma, pancreatic, breast, colon, ovarian, and small-cell lung carcinomas. The aberrant activation of the Hh signaling pathway is caused by mutations in the related genes (ligand-independent signaling or by the excessive expression of the Hh signaling molecules (ligand-dependent signaling – autocrine or paracrine. Several Hh signaling pathway inhibitors, such as vismodegib and sonidegib, have been developed for cancer treatment. These drugs are regarded as promising cancer therapies, especially for patients with refractory/advanced cancers.

Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy

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Emine Guven-Maiorov

2014-03-01

Full Text Available Cytokines are messengers between tissues and the immune system. They play essential roles in cancer initiation, promotion, metastasis, and immunotherapy. Structural pathways of cytokine signaling which contain their interactions can help understand their action in the tumor microenvironment. Here, our aim is to provide an overview of the role of cytokines in tumor development from a structural perspective. Atomic details of protein-protein interactions can help in understanding how an upstream signal is transduced; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists can change cellular consequences; why the same protein can lead to distinct outcomes, and which alternative parallel pathways can take over. They also help to design drugs/inhibitors against proteins de novo or by mimicking natural antagonists as in the case of interferon-γ. Since the structural database (PDB is limited, structural pathways are largely built from a series of predicted binary protein-protein interactions. Below, to illustrate how protein-protein interactions can help illuminate roles played by cytokines, we model some cytokine interaction complexes exploiting a powerful algorithm (PRotein Interactions by Structural Matching—PRISM.

Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy

International Nuclear Information System (INIS)

Guven-Maiorov, Emine; Acuner-Ozbabacan, Saliha Ece; Keskin, Ozlem; Gursoy, Attila; Nussinov, Ruth

2014-01-01

Cytokines are messengers between tissues and the immune system. They play essential roles in cancer initiation, promotion, metastasis, and immunotherapy. Structural pathways of cytokine signaling which contain their interactions can help understand their action in the tumor microenvironment. Here, our aim is to provide an overview of the role of cytokines in tumor development from a structural perspective. Atomic details of protein-protein interactions can help in understanding how an upstream signal is transduced; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists can change cellular consequences; why the same protein can lead to distinct outcomes, and which alternative parallel pathways can take over. They also help to design drugs/inhibitors against proteins de novo or by mimicking natural antagonists as in the case of interferon-γ. Since the structural database (PDB) is limited, structural pathways are largely built from a series of predicted binary protein-protein interactions. Below, to illustrate how protein-protein interactions can help illuminate roles played by cytokines, we model some cytokine interaction complexes exploiting a powerful algorithm (PRotein Interactions by Structural Matching—PRISM)

Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy

Energy Technology Data Exchange (ETDEWEB)

Guven-Maiorov, Emine; Acuner-Ozbabacan, Saliha Ece; Keskin, Ozlem; Gursoy, Attila [Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer Istanbul (Turkey); Nussinov, Ruth, E-mail: nussinor@helix.nih.gov [Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702 (United States); Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel)

2014-03-25

Cytokines are messengers between tissues and the immune system. They play essential roles in cancer initiation, promotion, metastasis, and immunotherapy. Structural pathways of cytokine signaling which contain their interactions can help understand their action in the tumor microenvironment. Here, our aim is to provide an overview of the role of cytokines in tumor development from a structural perspective. Atomic details of protein-protein interactions can help in understanding how an upstream signal is transduced; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists can change cellular consequences; why the same protein can lead to distinct outcomes, and which alternative parallel pathways can take over. They also help to design drugs/inhibitors against proteins de novo or by mimicking natural antagonists as in the case of interferon-γ. Since the structural database (PDB) is limited, structural pathways are largely built from a series of predicted binary protein-protein interactions. Below, to illustrate how protein-protein interactions can help illuminate roles played by cytokines, we model some cytokine interaction complexes exploiting a powerful algorithm (PRotein Interactions by Structural Matching—PRISM)

Prophylactic digitalization preoperatively of patients with arteriosclerotic heart disease.

Science.gov (United States)

Bille-Brahe, N E; Engell, H C; Sørensen, M B

1981-02-01

This study was undertaken to investigate the hemodynamic effect of prophylactic digitalization before major surgical procedures. Sixteen patients, all admitted for an elective vascular operation for arteriosclerotic disease and all with impaired left ventricular function, were investigated. In half of the patients, digitalis was given before the operation, the other half of the patients served as the control study. The measured parameters were pulmonary artery mean pressure, pulmonary capillary wedge pressure, central venous pressure, mean arterial blood pressure, heart rate, cardiac output, blood volume and arterial, as well as venous, oxygen content. Preoperatively, before digitalization, no significant differences were noted between the two groups at rest and during exercise. Before anesthesia and postoperatively, those given digitalis had improved cardiac function. Those in both groups, however, had a normal hemodynamic response to the surgical trauma. In this study, a definite answer is not provided concerning the usefulness of prophylactic digitalization but an increase in the ability of the digitalized heart to withstand the imposition of a pressure load postoperatively is suggested.

Complementary Roles of the Classical and Lectin Complement Pathways in the Defense against Aspergillus fumigatus

DEFF Research Database (Denmark)

Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine

2016-01-01

Aspergillus fumigatus infections are associated with a high mortality rate for immunocompromised patients. The complement system is considered to be important in protection against this fungus, yet the course of activation is unclear. The aim of this study was to unravel the role of the classical......, lectin, and alternative pathways under both immunocompetent and immunocompromised conditions to provide a relevant dual-perspective on the response against A. fumigatus. Conidia (spores) from a clinical isolate of A. fumigatus were combined with various human serum types (including serum deficient...... complement on A. fumigatus, but required classical and/or lectin pathway for initiation. In normal human serum, this initiation came primarily from the classical pathway. However, with a dysfunctional classical pathway (C1q-deficient serum), lectin pathway activated complement and mediated opsonophagocytosis...

Pharmacokinetic Variability of Drugs Used for Prophylactic Treatment of Migraine

DEFF Research Database (Denmark)

Tfelt-Hansen, Peer; Ågesen, Frederik Nybye; Pavbro, Agniezka

2017-01-01

In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum...

Role of nitric oxide pathway in the conditioned rewarding effects of MDMA in mice.

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García-Pardo, M P; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

2017-07-14

It is estimated that 2.1 million young adults used MDMA/Ecstasy in the last year in Europe. Vulnerable subjects can develop dependence after MDMA abuse but currently there does not exist an effective treatment for this disorder. The nitric oxide (NO) pathway seems to have an important role on the rewarding effects of different drugs and has been proposed as a new pharmacological treatment for psychostimulant addiction. In the present study, we intend to evaluate whether the blockade of the NO synthesis (NOS) interferes with the rewarding effects of MDMA in the conditioned preference place (CPP) paradigm in young adult male mice. Our results indicated that mice treated with 7-nitroindazole (a NOS inhibitor) did not show CPP after conditioning with MDMA (1.25mg/kg). These results demonstrated the role of the NO pathway in the rewarding effects of MDMA and suggested that the manipulation of this pathway could be a new therapeutic option for MDMA abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluating quality of life and cost implications of prophylactic radiotherapy in mesothelioma: Health economic analysis of the SMART trial.

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Stewart, Samuel Alan; Clive, Amelia O; Maskell, Nick A; Penz, Erika

2018-01-01

The SMART trial is a UK-based, multicentre RCT comparing prophylactic radiotherapy and symptom-based (deferred) radiotherapy in 203 patients with Malignant Pleural Mesothelioma who had undergone large bore pleural interventions. Using costs and quality of life data collected alongside the clinical trial, we will estimate the cost-effectiveness of prophylactic radiotherapy compared to deferred radiotherapy over a 1-year period. Healthcare utilization and costs were captured during the trial. Utility weights produced by the EQ-5D questionnaire were used to determine quality-adjusted life-years (QALY) gained. The incremental cost-effectiveness ratio was calculated over the one-year trial period. Costs were similar in the immediate and deferred radiotherapy groups: £5480.40 (SD = £7040; n = 102) and £5461.40 (SD = £7770; n = 101) respectively. There was also no difference in QALY: 0.498 (95% CI: [0.45, 0.547]) in the prophylactic radiotherapy group versus 0.525 (95% CI: [0.471, 0.580]) in the deferred group. At a willingness to pay threshold of £30,000/QALY there was only a 24% chance that prophylactic radiotherapy was cost-effective compared to deferred radiotherapy. There was no significant effect of prophylactic radiotherapy on quality of life in the intervention group, nor was there any discernable decrease in healthcare costs. There is little evidence to suggest that prophylactic radiotherapy is a cost-effective intervention in this population. ISRCTN72767336 with ISRCTN.

Evaluating quality of life and cost implications of prophylactic radiotherapy in mesothelioma: Health economic analysis of the SMART trial.

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Samuel Alan Stewart

Full Text Available The SMART trial is a UK-based, multicentre RCT comparing prophylactic radiotherapy and symptom-based (deferred radiotherapy in 203 patients with Malignant Pleural Mesothelioma who had undergone large bore pleural interventions. Using costs and quality of life data collected alongside the clinical trial, we will estimate the cost-effectiveness of prophylactic radiotherapy compared to deferred radiotherapy over a 1-year period.Healthcare utilization and costs were captured during the trial. Utility weights produced by the EQ-5D questionnaire were used to determine quality-adjusted life-years (QALY gained. The incremental cost-effectiveness ratio was calculated over the one-year trial period.Costs were similar in the immediate and deferred radiotherapy groups: £5480.40 (SD = £7040; n = 102 and £5461.40 (SD = £7770; n = 101 respectively. There was also no difference in QALY: 0.498 (95% CI: [0.45, 0.547] in the prophylactic radiotherapy group versus 0.525 (95% CI: [0.471, 0.580] in the deferred group. At a willingness to pay threshold of £30,000/QALY there was only a 24% chance that prophylactic radiotherapy was cost-effective compared to deferred radiotherapy.There was no significant effect of prophylactic radiotherapy on quality of life in the intervention group, nor was there any discernable decrease in healthcare costs. There is little evidence to suggest that prophylactic radiotherapy is a cost-effective intervention in this population.ISRCTN72767336 with ISRCTN.

Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.

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Clifford Liongue

Full Text Available BACKGROUND: Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK-Signal transducer and activator of transcription (STAT pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP, Protein inhibitors against Stats (PIAS, and Suppressor of cytokine signaling (SOCS proteins across a diverse range of organisms. RESULTS: Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components. CONCLUSION: Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

Prophylactic Groin Wound Vacuum-assisted Therapy in Vascular Surgery Patients at Enhanced Risk for Postoperative Wound Infection.

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Pesonen, Luke O; Halloran, Brian G; Aziz, Abdulhameed

2018-01-01

Vascular groin wounds have higher than expected surgical site infection (SSI) rates and some patients are at enhanced risk. The Wiseman et al. paper suggests an objective scoring system that identifies patients at enhanced risk of postdischarge SSI. We hypothesize that prophylactic groin wound vacuum-assisted closure (VAC) therapy in enhanced risk patients will decrease SSI and readmission and the Wiseman model provides potential evidence that enhanced risk patients can be objectively identified. A single institution, retrospective analysis was conducted from January 2013 to September 2016 utilizing procedure codes to identify patients with wound VACs placed in the operating room. Two distinct groups were identified. The first was a wound complication patient group with 15 limbs (13 patients) with a groin wound VAC placed within 45 days postoperatively for groin wound complications. Eleven of these limbs had the VAC placed at readmission. The second group was a prophylactic patient group that included 8 limbs (7 patients) who received a VAC prophylactically placed in the enhanced risk wounds. These wounds were determined to be enhanced risk based on clinical criteria judged by the operating surgeon such as a large overhanging panniculus and/or one of several ongoing medical issues. We calculated a Wiseman score for all patients, determined total cost of the readmissions, and determined 30-day postsurgical SSI incidence for the prophylactic VAC group. Per the Wiseman scores, 9 limbs with postoperative complications were high risk and 3 limbs were moderate/high risk. Eleven limbs had a VAC placed at readmission with an average readmission cost of $8876.77. For the prophylactic group, 8 limbs were high risk with no observed postdischarge SSI in the first 30 days from surgery. The Wiseman scores showed close correlation between the retrospective high and moderate/high risk groups versus the prophylactic VAC group (31.5 ± 7.3 vs. 32 ± 5.5, P = 0.87). The Wiseman

Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: A Cochrane Review

International Nuclear Information System (INIS)

Lester, Jason Francis; MacBeth, Fergus R.; Coles, Bernadette

2005-01-01

Purpose: To investigate whether prophylactic cranial irradiation (PCI) has a role in the management of patients with non-small-cell lung cancer (NSCLC) treated with curative intent. Methods and Materials: A search strategy was designed to identify randomized controlled trials (RCTs) comparing PCI with no PCI in NSCLC patients treated with curative intent. The electronic databases MEDLINE, EMBASE, LILACS, and Cancerlit were searched, along with relevant journals, books, and review articles to identify potentially eligible trials. Four RCTs were identified and reviewed. A total of 951 patients were randomized in these RCTs, of whom 833 were evaluable and reported. Forty-two patients with small-cell lung cancer were excluded, leaving 791 patients in total. Because of the small patient numbers and trial heterogeneity, no meta-analysis was attempted. Results: Prophylactic cranial irradiation did significantly reduce the incidence of brain metastases in three trials. No trial reported a survival advantage with PCI over observation. Toxicity data were poorly collected and no quality of life assessments were carried out in any trial. Conclusion: Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit. It was not possible to evaluate whether any radiotherapy regimen is superior, and the effect of PCI on quality of life is not known. There is insufficient evidence to support the use of PCI in clinical practice. Where possible, patients should be offered entry into a clinical trial

Market researches on demand for dietary and prophylactic nutrition in the Saratov Region

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Nikitinа T. A.

2016-09-01

Full Text Available In competitive and constantly changing market conditions special attention has been paid to market researches. The results of these studies become the basis for formation of sales estimates, and projected levels of revenues and profits from sales. Market researches are the essential condition to make offered goods successful at the market. It is market researches that help companies to realize the control of consumers' needs changing. The market researches on demand for dietary and prophylactic nutrition in the Saratov Region have been the research objective. In accordance with the given objective the following goals have been formed: 1 finding out the most spread diseases among the population; 2 determination of the average age of people suffering from one or another disease; 3 studying demand of products with food fiber additives; 4 analysis of respondent's preference regarding the addition of natural vegetable additives to foodstuff; 5 demand for dietary and prophylactic foodstuff among the population. Since the survey has been carried out among people suffering from various diseases, particular attention during the market research has been turned to the medical and prophylactic properties of food fibers to find out the attitude of the respondents to functional foodstuff. The dynamics of noninfectious diseases, the population health status depending on age, and increase of overweight people during 2012–2014 have been shown. As a result of questionnaire data processing it has been ascertained that the population is of low awareness regarding the necessity to consume foodstuff with radioprotective and chelator properties. The researches have demonstrated that dietary and prophylactic foodstuff is in demand and consequently the development of such products is reasonable.

Evidence-based analysis of prophylactic treatment of asymptomatic retinal breaks and lattice degeneration.

Science.gov (United States)

Wilkinson, C P

2000-01-01

To assess the quality of information in the literature regarding the benefits of prophylactic treatment of asymptomatic retinal tears and lattice degeneration. Asymptomatic retinal breaks occur in approximately 7% of patients over age 40, and lattice degeneration is present in approximately 8% of the general population. Because retinal breaks cause retinal detachment and lattice degeneration is associated with approximately 30% of retinal detachments, prophylactic treatment of these lesions has sometimes been recommended. A panel of vitreoretinal experts performed a literature review of all publications regarding prevention of retinal detachment that have been published in English. These articles were then used to prepare recommendations for patient care in an American Academy of Ophthalmology Preferred Practice Pattern (PPP). Each recommendation was rated according to: (1) its importance in the care process and (2) the strength of evidence supporting the given recommendation. Most recommendations were rated as A (most important to patient care). Only a single publication was graded as I (providing strong evidence in support of a recommendation), and this was not a prospective trial. Of the few publications rated as II (substantial evidence), most were studies documenting a lack of treatment benefit. Because of an absence of level I and level II studies in the literature, level III (consensus of expert opinion) was the basis for most recommendations in the PPP. The current literature regarding prevention of retinal detachment does not provide sufficient information to support strongly prophylactic treatment of lesions other than symptomatic flap tears. Prospective randomized trials of prophylactic therapy are indicated. Eyes highly predisposed to retinal detachment should be considered for such studies.

Effectiveness of prophylactic percutaneous endoscopic gastrostomy for oropharyngeal cancer patients undergoing concurrent chemoradiotherapy

International Nuclear Information System (INIS)

Teshima, Masanori; Tanimoto, Hitoshi; Saito, Miki; Otsuki, Naoki; Sasaki, Ryohei; Kiyota, Naomi; Okuno, Shinya; Nibu, Ken-ichi

2009-01-01

Patients with head and neck carcinoma are often provided concurrent chemoradiotherapy (CCRT), but they experience severe mucositis and dysphagia. These side effects can lead to decreased oral intake, resulting in interruption of treatment. In our hospital, from September 2007, all patients with oropharyngeal cancer who were to receive CCRT, were principally offered percutaneous endoscopic gastrostomy (PEG) before the start of treatment, and tube feeding was started when swallowing became impaired, to accomplish the treatment as planned. To evaluate the effect of prophylactic PEG, outcome measures in this study included the frequency of unplanned break from CCRT, nutritional deterioration and required analgesic during CCRT, complication of PEG, and patient satisfaction between 15 patients with PEG and 11 patients without PEG as a control group. Although no significant weight loss occurred in either group, there were fewer patients with a Body Mass Index <18.5 in the PEG group after CCRT than in the control group. Regarding the treatment, most patients were satisfied with their PEG and considered that prophylactic PEG was necessary and helpful in completing the CCRT. This study suggests that prophylactic PEG helps patients to complete CCRT both mentally and nutritionally. (author)

Supraventricular tachyarrhythmias after myocardial revascularization: a randomized trial of prophylactic digitalization.

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Tyras, D H; Stothert, J C; Kaiser, G C; Barner, H B; Codd, J E; Willman, V L

1979-02-01

The success of prophylactic digitalization in reducing the incidence of supraventricular tachyarrhythmias (SVT) was studied in 140 randomly grouped, consecutive patients undergoing myocardial revascularization operations. The test group received either 1 or 1.5 mg. of digoxin the day before operation and were maintained postoperatively on 0.25 mg. of digoxin daily. There was a significant increase (p less than 0.05) in the incidence of SVT in the treated patients (17 of 61 or 27.8 percent) vs. the untreated patients (nine of 79 or 11.4 percent). There was no significant difference in SVT with the two digitalization dosage levels (31.6 percent with 1 mg. vs. 21.7 percent with 1.5 mg.). Prophylactic digitalization demonstrates no benefit in the prevention of SVT following myocardial revascularization and may, in fact, predispose the patient to these arrhythmias.

Radioembolization : Is Prophylactic Embolization of Hepaticoenteric Arteries Necessary? A Systematic Review

NARCIS (Netherlands)

Borggreve, Alicia S; Landman, Anadeijda J E M C; Vissers, Coco M J; De Jong, Charlotte D; Lam, Marnix G E H; Monninkhof, Evelyn M; Prince, Jip F

2016-01-01

PURPOSE: To study the effectiveness of prophylactic embolization of hepaticoenteric arteries to prevent gastrointestinal complications during radioembolization. METHODS: A PubMed, Embase and Cochrane literature search was performed. We included studies assessing both a group of patients with and

Encephalitic Sarcocystosis and its Prophylactic Treatment in Sheep

OpenAIRE

ÖZMEN, Özlem; ŞAHİNDURAN, Şima; HALIGÜR, Mehmet; YUKARI, Bayram Ali; DORRESTEIN, Gerry M.

2014-01-01

The aim of this study was to examine the clinical and pathological findings in sheep naturally infected with severe encephalitic sarcocystosis and to evaluate the prophylactic effect of amprolium on the disease. From a flock of approximately 350 animals, 10 sheep were referred to the Veterinary Faculty Clinic with neurological symptoms that developed during the previous 2 weeks. These 10 sheep were clinically and pathologically examined, and the remaining animals in the flock without neurolog...

Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients

NARCIS (Netherlands)

Hartong, EGTM; Moleman, P; Hoogduin, CAL; Broekman, TG; Nolen, WA

Background: Alternatives to lithium for prophylactic treatment of patients with bipolar affective disorders are increasingly being advocated. However, trials comparing lithium with alternatives are scarce and often biased. Method: We studied 94 patients with at least 2 episodes of bipolar disorder

The Role of Prophylactic Endoscopic Sphincterotomy for Prevention of Postoperative Bile Leak in Hydatid Liver Disease: A Randomized Controlled Study.

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El-Gendi, Ahmed M; El-Shafei, Mohamed; Bedewy, Essam

2018-03-12

Bile leak is the main cause of morbidity and mortality after surgery for hydatid liver cysts. Aim was to assess the role of prophylactic endoscopic sphincterotomy (ES) in reducing postoperative bile leak in patients undergoing partial cystectomy. Fifty-four patients with hepatic hydatid cyst met inclusion criteria, 27 were excluded or declined to participate. Twenty-six women and 28 men (mean age 44.6 ± 10.1, range: 22-61 years) were randomly assigned to either group I with ES (n = 27) or group II without ES (n = 27). Demographics and clinical, laboratory, and radiological characteristics of cysts were not statistically different between two groups. Group I had a significant decrease in bile leak rate compared with group II (11.1% versus 40.7%, P = .013), with significantly shorter duration of hospital stay (P leak in 3-4 days without intervention. Biliary fistula in group II had a significantly higher need for biliary intervention through postoperative endoscopic retrograde cholangiopancreatography with ES compared with biliary fistula in group I ( FE P = .002), with significantly longer mean time of fistula closure (P = .011) and longer time to drain removal (P leak rate with shorter hospital stay after partial cystectomy of hydatid cyst. Biliary fistula in patients with ES has significantly lower daily output with shorter time of drain removal and shorter time to closure than patients without ES.

Prophylactic treatment of the fellow eye of patients with retinal detachment: a retrospective study.

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Avitabile, Teresio; Bonfiglio, Vincenza; Reibaldi, Michele; Torrisi, Benedetto; Reibaldi, Alfredo

2004-03-01

Controversy exists over the prophylactic treatment of predisposing lesions to prevent retinal detachment. Seven hundred sixty consecutive phakic fellow eyes with rhegmatogenous retinal detachment in the first eye were examined by the same vitreoretinal surgeon before detachment surgery and for a follow-up period ranging from 1 to 72 months, with a mean of 36 months. During this period, in 305 fellow eyes (40.1%) predisposing retinal lesions were present and prophylactic treatments (photocoagulation, cryotherapy or scleral buckle) were performed independently of vitreous status. The results were then compared with the incidence of bilateral RD without prophylaxis reported in Folk and Burton's study of 1982; the two study's data were well matched and showed no significant difference in regards to age, sex, incidence myopia > or =-2.5 and incidence of lattice degeneration. The objective was to investigate whether or not prophylactic treatment is able to avert retinal detachment in the fellow eye. The age of the patients with peripheral retinal lesions was correlated inversely with the presence of myopia. Nine eyes out of 305 eyes treated (2.9%) developed a retinal detachment, reducing the rate of bilateral retinal detachment to 1.2% (9 eyes out of 760). This incidence of bilaterality (1.2%) was lower than the incidence of retinal detachment in fellow eyes not prophylactically treated as reported in the literature, and there exists a highly statistically significant difference between this study's data of 1.2% after prophylaxis and a 13.4% rate of bilaterality as reported by Folk without prophylaxis (P=0.0000).

Comparison of intelligence quotient in children surviving leukemia who received different prophylactic central nervous system treatments

OpenAIRE

Nahid, Reisi; Leila, Khalilian

2012-01-01

Background: Neurocognitive deficits and decrease in intelligence quotient (IQ) is one of the complication of prophylactic central nervous system (CNS) treatment in acute lymphoblastic leukemia (ALL) patients. In this study, we compare the IQ in survivors of ALL that were treated with different prophylactic CNS treatments. Materials and Methods : We compared 43 long-term survivors of ALL: 21 survivors with intrathecal methotrexate (IT MTX) as CNS prophylaxis, 22 with IT MTX+1800-2400 rads c...

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

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Chiurillo, Miguel Angel

2015-01-01

Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancer-related deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/β-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors (mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput “omics” approaches will help in the search for Wnt pathway antagonist in the near future. PMID:25992323

Effects of Prophylactic Knee Bracing on Lower Limb Kinematics, Kinetics, and Energetics During Double-Leg Drop Landing at 2 Heights.

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Ewing, Katie A; Begg, Rezaul K; Galea, Mary P; Lee, Peter V S

2016-07-01

Anterior cruciate ligament (ACL) injuries commonly occur during landing maneuvers. Prophylactic knee braces were introduced to reduce the risk of ACL injuries, but their effectiveness is debated. We hypothesized that bracing would improve biomechanical factors previously related to the risk of ACL injuries, such as increased hip and knee flexion angles at initial contact and at peak vertical ground-reaction force (GRF), increased ankle plantar flexion angles at initial contact, decreased peak GRFs, and decreased peak knee extension moment. We also hypothesized that bracing would increase the negative power and work of the hip joint and would decrease the negative power and work of the knee and ankle joints. Controlled laboratory study. Three-dimensional motion and force plate data were collected from 8 female and 7 male recreational athletes performing double-leg drop landings from 0.30 m and 0.60 m with and without a prophylactic knee brace. GRFs, joint angles, moments, power, and work were calculated for each athlete with and without a knee brace. Prophylactic knee bracing increased the hip flexion angle at peak GRF by 5.56° (P knee flexion angle at peak GRF by 4.75° (P = .001), and peak hip extension moment by 0.44 N·m/kg (P knee and ankle. No differences in peak GRFs and peak knee extension moment were observed with bracing. The application of a prophylactic knee brace resulted in improvements in important biomechanical factors associated with the risk of ACL injuries. Prophylactic knee braces may help reduce the risk of noncontact knee injuries in recreational and professional athletes while playing sports. Further studies should investigate different types of prophylactic knee braces in conjunction with existing training interventions so that the sports medicine community can better assess the effectiveness of prophylactic knee bracing. © 2016 The Author(s).

Analysis of occupational risk and antirrabies prophylactic treatment in health and endemic agents

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Moisés Tenório Ferrer

2014-09-01

Full Text Available ABSTRACT. Ferrer M.T., de Melo S.R., Pimentel J. de L., Pinheiro Junior J.W. & Brandespim D.F. [Analysis of occupational risk and antirrabies prophylactic treatment in health and endemic agents.] Análise do risco ocupacional e do tratamento profilático antirrábico em agentes de endemia e de saúde. Revista Brasileira de Medicina Veterinária, 36(3:307-311, 2014. Curso de Medicina Veterinária, Unidade Acadêmica de Garanhuns, Universidade Federal Rural de Pernambuco, Av. Bom Pastor, s/n°, Boa Vista, Garanhuns, PE 55292-270, Brasil. E-mail: moises.vet@hotmail.com This paper aimed to assess the risk of exposure and conduct of prophylactic antirrabies treatment established by health care providers and the endemics Municipality of Garanhuns, PE during their professional activities. We conducted a descriptive epidemiological study of retrospective type, from data collection through the application of a semi-structured questionnaire containing open and closed questions, to 192 professionals, 168 health agents and 24 agents of the municipality of endemics Garanhuns -PE. Of the 192 interviewed agents, 14.1% (27/165 had been attacked by animals during their occupation activities. On the post-exposure prophylactic treatment, it was found that 44.5% (12/27 received-vaccination serum, 37% (10/27 did not undergo any treatment, while only 18.5% (5/27 had the wound washed with soap and water. Was concluded that there is a lack of basic information regarding both the pre-exposure or post-exposure prophylaxis of rabies in professionals like agents that act with both health and / or endemic diseases and it is suggested both the improvement of their professional skills as the preexposure immunization as prophylactic measure to minimize the occupational risk in function of their field activities.

Prophylactic amnioinfusion for intrapartum oligohydramnios: a meta-analysis of randomized controlled trials.

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Pitt, C; Sanchez-Ramos, L; Kaunitz, A M; Gaudier, F

2000-11-01

To evaluate the effectiveness of intrapartum prophylactic amnioinfusion in pregnancies complicated by oligohydramnios. Randomized controlled trials of prophylactic amnioinfusion in women with oligohydramnios were identified using computerized databases, index reviews, and references cited in original studies and review articles. We evaluated, abstracted data from, and analyzed randomized studies of prophylactic intrapartum amnioinfusion in women with oligohydramnios. In every study the group allocation was based exclusively on presence of oligohydramnios. Only published studies with clearly documented outcome data were included. The quality of each trial was evaluated for methodology, inclusion and exclusion criteria, adequacy of randomization, amnioinfusion protocols, definition of outcomes, and statistical analyses. The trials were evaluated concerning cesarean deliveries for fetal heart rate (FHR) abnormalities, overall cesarean rates, acidemia at birth, intrapartum fetal heart rate abnormalities, Apgar scores under 7 at 5 minutes, and postpartum endometritis. Thirty-five studies were identified, of which 14 met the inclusion criteria for this systematic review. They included 1533 patients, 793 in the amnioinfusion group, and 740 controls. Odds ratios (OR) with their 95% confidence intervals (CI) for each outcome were calculated. We calculated an estimate of the OR and risk difference for dichotomous outcomes using random and fixed-effects models. A test of homogeneity was done across studies. Women with oligohydramnios who received intrapartum amnioinfusion had lower incidence of cesarean for FHR abnormalities (OR 0.23; 95% CI 0.15, 0.35). Intrapartum amnioinfusion also was associated with lower overall rates of cesarean deliveries (OR 0.52; 95% CI 0.40, 0. 68), acidemia at birth (OR 0.40; 95% CI 0.30, 0.55), FHR abnormalities during labor (OR 0.24; 95% CI 0.17, 0.34), and Apgar scores under 7 at 5 minutes (OR 0.52; 95% CI 0.29, 0.91). Postpartum endometritis

Unhealthy smokers: scopes for prophylactic intervention and clinical treatment.

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Prasad, Shikha; Kaisar, Mohammad Abul; Cucullo, Luca

2017-10-04

Globally, tobacco use causes approximately 6 million deaths per year, and predictions report that with current trends; more than 8 million deaths are expected annually by 2030. Cigarette smokings is currently accountable for more than 480,000 deaths each year in United States (US) and is the leading cause of preventable death in the US. On average, smokers die 10 years earlier than nonsmokers and if smoking continues at its current proportion among adolescents, one in every 13 Americans aged 17 years or younger is expected to die prematurely from a smoking-related illness. Even though there has been a marginal smoking decline of around 5% in recent years (2005 vs 2015), smokers still account for 15% of the US adult population. What is also concerning is that 41,000 out of 480,000 deaths results from secondhand smoke (SHS) exposure. Herein, we provide a detailed review of health complications and major pathological mechanisms including mutation, inflammation, oxidative stress, and hemodynamic and plasma protein changes associated with chronic smoking. Further, we discuss prophylactic interventions and associated benefits and provide a rationale for the scope of clinical treatment. Considering these premises, it is evident that much detailed translational and clinical studies are needed. Factors such as the length of smoking cessation for ex-smokers, the level of smoke exposure in case of SHS, pre-established health conditions, genetics (and epigenetics modification caused by chronic smoking) are few of the criteria that need to be evaluated to begin assessing the prophylactic and/or therapeutic impact of treatments aimed at chronic and former smokers (especially early stage ex-smokers) including those frequently subjected to second hand tobacco smoke exposure. Herein, we provide a detailed review of health complications and major pathological mechanisms including mutation, inflammation, oxidative stress, and hemodynamic and plasma protein changes associated with

The Use of Sentinel Lymph Node Biopsy in BRCA1/2 Mutation Carriers Undergoing Prophylactic Mastectomy: A Retrospective Consecutive Case-Series Study

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Sara Câmara

2018-01-01

Full Text Available Introduction. Sentinel lymph node biopsy in prophylactic mastectomy is controversial. It avoids lymphadenectomy in occult carcinoma but is associated with increased morbidity. Women with BRCA mutations have a higher incidence of occult carcinoma and our objective was to assess the clinical utility of sentinel lymph node biopsy when these women undergo prophylactic mastectomy. Materials and Methods. Seven-year retrospective consecutive case-series study of women, with a BRCA deleterious mutation, admitted to prophylactic mastectomy, at our center. Breast MRI < 6 months before surgery was routine, unless contraindicated. Results. Fifty-seven patients (43% BRCA1; 57% BRCA2 underwent 80 prophylactic mastectomies. 72% of patients had had breast cancer treated before prophylactic mastectomy or synchronously to it. The occult carcinoma incidence was 5%, and half of the cases were invasive. SLNB was performed in 19% of the prophylactic mastectomies; none of these had tumor invasion. Women with invasive carcinoma who had not undergone sentinel lymph node biopsy were followed closely with axillary ultrasound. The median follow-up was 37 months, with no local recurrence; 1 patient died of primary tumor systemic relapse. Conclusions. Our data do not support this procedure for routine (in agreement with previous literature, in this high risk for occult carcinoma population.

Prophylactic and metaphylactic antimicrobial use in Belgian fattening pig herds.

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Callens, Bénédicte; Persoons, Davy; Maes, Dominiek; Laanen, Maria; Postma, Merel; Boyen, Filip; Haesebrouck, Freddy; Butaye, Patrick; Catry, Boudewijn; Dewulf, Jeroen

2012-09-01

The monitoring of antimicrobial use is an essential step to control the selection and spread of antimicrobial resistance. Between January and October 2010 data on prophylactic and metaphylactic antimicrobial use were collected retrospectively on 50 closed or semi-closed pig herds. Ninety-three percent of the group treatments were prophylactic whereas only 7% were methaphylactic. The most frequently used antimicrobials orally applied at group level were colistin (30.7%), amoxicillin (30.0%), trimethoprim-sulfonamides (13.1%), doxycycline (9.9%) and tylosin (8.1%). The most frequently applied injectable antimicrobials were tulathromycin (45.0%), long acting ceftiofur (40.1%) and long acting amoxicillin (8.4%). The treatment incidences (TI) based on the used daily dose pig (UDD(pig) or the actually administered dose per day per kg pig of a drug) for all oral and injectable antimicrobial drugs was on average 200.7 per 1000 pigs at risk per day (min=0, max=699.0), while the TI based on the animal daily dose pig (ADD(pig) or the national defined average maintenance dose per day per kg pig of a drug used for its main indication) was slightly higher (average=235.8, min=0, max=1322.1). This indicates that in reality fewer pigs were treated with the same amount of antimicrobials than theoretically possible. Injectable products were generally overdosed (79.5%), whereas oral treatments were often underdosed (47.3%). In conclusion, this study shows that prophylactic group treatment was applied in 98% of the visited herds and often includes the use of critically important and broad-spectrum antimicrobials. In Belgium, the guidelines for prudent use of antimicrobials are not yet implemented. Copyright © 2012 Elsevier B.V. All rights reserved.

Prophylactic Antibiotics for Endoscopy-Associated Peritonitis in Peritoneal Dialysis Patients

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Wu, Hsin-Hsu; Li, I-Jung; Weng, Cheng-Hao; Lee, Cheng-Chia; Chen, Yung-Chang; Chang, Ming-Yang; Fang, Ji-Tseng; Hung, Cheng-Chieh; Yang, Chih-Wei; Tian, Ya-Chung

2013-01-01

Introduction Continuous ambulatory peritoneal dialysis (CAPD) peritonitis may develop after endoscopic procedures, and the benefit of prophylactic antibiotics is unclear. In the present study, we investigated whether prophylactic antibiotics reduce the incidence of peritonitis in these patients. Patients and methods We retrospectively reviewed all endoscopic procedures, including esophagogastroduodenoscopy (EGD), colonoscopy, sigmoidoscopy, cystoscopy, hysteroscopy, and hysteroscopy-assisted intrauterine device (IUD) implantation/removal, performed in CAPD patients at Chang Gung Memorial Hospital, Taiwan, between February 2001 and February 2012. Results Four hundred and thirty-three patients were enrolled, and 125 endoscopies were performed in 45 patients. Eight (6.4%) peritonitis episodes developed after the examination. Antibiotics were used in 26 procedures, and none of the patients had peritonitis (0% vs. 8.1% without antibiotic use; p = 0.20). The peritonitis rate was significantly higher in the non-EGD group than in the EGD group (15.9% [7/44] vs. 1.2% [1/81]; pperitonitis rate compared to that without antibiotic use (0% [0/16] vs. 25% [7/28]; pPeritonitis only occurred if invasive procedures were performed, such as biopsy, polypectomy, or IUD implantation, (noninvasive procedures, 0% [0/20] vs. invasive procedures, 30.4% [7/23]; pperitonitis was noted if antibiotics were used prior to examination with invasive procedures (0% [0/10] vs. 53.8% [7/13] without antibiotic use; pperitonitis (antibiotics, 0% [0/4] vs. no antibiotics, 55.6% [5/9]; p = 0.10). Conclusion Antibiotic prophylaxis significantly reduced endoscopy-associated PD peritonitis in the non-EGD group. Endoscopically assisted invasive procedures, such as biopsy, polypectomy, IUD implantation/removal, and dilatation and curettage (D&C), pose a high risk for peritonitis. Prophylactic antibiotics for peritonitis prevention may be required in colonoscopic procedures and gynecologic procedures

Prophylactic effect of paw-paw leaf and bitter leaf extracts on the ...

African Journals Online (AJOL)

Vernonia amygdalina) were used to investigate their prophylactic effects on the incidence of myco-pathogens of groundnut in. Ishiagu, south eastern Nigeria. Two field experiments were conducted: pre-soaking of the seeds before sowing and ...

Prophylactic effects of elastin peptide derived from the bulbus arteriosus of fish on vascular dysfunction in spontaneously hypertensive rats.

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Takemori, Kumiko; Yamamoto, Ei; Ito, Hiroyuki; Kometani, Takashi

2015-01-01

To determine the prophylactic effects of an elastin peptide derived from the bulbus arteriosus of bonitos and prolylglycine (PG), a degradation product of elastin peptide, on vascular dysfunction in spontaneously hypertensive rats (SHRs). Male 15-week-old SHR/Izm rats were fed without (control group) or with elastin peptide (1 g/kg body weight) for 5 weeks (EP group), or were infused via an osmotic mini-pump for 4 weeks with PG (PG group) or saline (control group). Using thoracic aortas, we assessed endothelial changes by scanning electron microscopy. Vascular reactivity (contraction and relaxation) and pressure-induced distension was compared. mRNA production levels of endothelial nitric oxide synthase (eNOS) and intercellular adhesion molecule-1 (ICAM-1) were investigated by real-time-polymerase chain reaction. Aortas of the EP group displayed limited endothelial damage compared with that in the control group. Under treatment of SHRs with elastin peptide, the effect of phenylephrine returned closer to the normal level observed in normotensive Wistar-Kyoto (WKY/Izm) rats. mRNA production of eNOS (but not ICAM-1) was greater in the EP group than in the control group. Endothelial damage was suppressed and pressure-induced vascular distension was greater in the PG group than in the corresponding control group. These results suggest that elastin peptide from bonitos elicits prophylactic affects hypertension-associated vascular dysfunction by targeting the eNOS signaling pathway. PG may be a key mediator of the beneficial effects of elastin peptide. Copyright © 2014 Elsevier Inc. All rights reserved.

Pain from copper intrauterine device insertion: randomized trial of prophylactic ibuprofen.

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Hubacher, David; Reyes, Veronica; Lillo, Sonia; Zepeda, Ana; Chen, Pai-Lien; Croxatto, Horacio

2006-11-01

This study was undertaken to determine whether 400 mg of prophylactic ibuprofen can alleviate pain from insertion of an intrauterine device (IUD) and to measure level of pain with improved techniques. We conducted a randomized, double-blind, placebo-controlled trial of 2019 first-time IUD users: 1008 women received placebo and 1011 women received 400 mg of ibuprofen. Participants took the single tablet at least 45 minutes before IUD insertion. Immediately after insertion, participants recorded level of pain by using a 10-cm visual analog scale, with the value of 10 meaning "worst imaginable pain." Median level of pain was 1.0 for both ibuprofen and placebo participants; rank test statistics confirmed no difference. Some subgroups of women experienced higher pain (eg, nulliparous women), but ibuprofen still had no important impact on level of pain. Even among first-time users, pain from IUD insertion is generally low. Prophylactic ibuprofen as used in this protocol does not reduce IUD insertion pain.

[Prophylactic requirements for sanitary and epidemiological surveillance in dentistry].

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Kaplan, B M; Maksimenko, L V; Fedotova, N N; Gololobova, T V; Konovalov, O E

2009-01-01

The paper outlines the requirements for sanitary-and-epidemiological surveillance to prevent dental diseases. The investigations pose tasks to medical prevention centers to solve the problems in tooth prophylaxis, such as organizational-and-methodological, sanitary-and-educational, health-improving, and others. The sanitary-and-hygienic requirements for therapeutic-and-prophylactic dental facilities are defined. A procedure for keeping a management protocol for the prevention of tooth diseases is described.

Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.

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Sun, Yu-Yo; Li, Yikun; Wali, Bushra; Li, Yuancheng; Lee, Jolly; Heinmiller, Andrew; Abe, Koji; Stein, Donald G; Mao, Hui; Sayeed, Iqbal; Kuan, Chia-Yi

2015-07-01

Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis. © 2015 American Heart Association, Inc.

Prophylactic dialysis in non-dialysis-dependent patients with renal failure after CABG

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Roghayyeh Borji

2014-03-01

Conclusion: According the results of this study, prophylactic dialysis, before conduct-ing CABG, does not have any significant effect on mortality and other complications. The only exception is lung complications in non-dialysis-dependent patients with renal failure.

Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV: Developments and Future Perspectives

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Marian E. Major

2009-08-01

Full Text Available Studies in patients and chimpanzees that spontaneously clear Hepatitis C Virus (HCV have demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism regarding prophylactic HCV vaccines and a number of studies in the chimpanzee model have been performed, all of which resulted in modified infections after challenge but did not always prevent persistence of the virus. Therapeutic vaccine strategies have also been pursued in an effort to reduce the costs and side effects associated with anti-viral drug treatment. This review summarizes the studies performed thus far in both patients and chimpanzees for prophylactic and therapeutic vaccination, assesses the progress made and future perspectives.

Prophylactic efficacy of lithium administered every second day: a WHO multicentre study

DEFF Research Database (Denmark)

Plenge, P; Amin, M; Agarwal, A K

1999-01-01

OBJECTIVES: To study the prophylactic efficacy of lithium administered every second day to patients with bipolar disorder or recurrent unipolar depressive disorder. METHODS: The study was carried out as a WHO multicentre study in five different psychiatric clinics: Russia (Moscow), Canada (Montreal......), India (Lucknow), Germany (Munich) and South Korea (Pusan), with the lithium tablets being supplied from Denmark (Copenhagen). Participation in the study was conditional on the patient having been in prophylactic lithium treatment for the preceding 2-year period and having been free of depressive...... of bipolar disorder and five with a diagnosis of recurrent unipolar depressive disorder, participated in the study. The number of patients from each centre ranged from six to 11. The mean lithium dose every second day was 36 mmol lithium, leading to a mean 12-h standard serum lithium concentration during...

Cost and effectiveness evaluation of prophylactic HPV vaccine in developing countries.

Science.gov (United States)

Termrungruanglert, Wichai; Havanond, Piyalamporn; Khemapech, Nipon; Lertmaharit, Somrat; Pongpanich, Sathirakorn; Khorprasert, Chonlakiet; Taneepanichskul, Surasak

2012-01-01

Approximately 80% of cervical cancer cases occur in developing countries. In Thailand, cervical cancer has been the leading cancer in females, with an incidence of 24.7 cases per 100,000 individuals per year. We constructed a decision model to simulate the lifetime economic impact for women in the context of human papillomavirus (HPV) infection prevention. HPV-related diseases were of interest: cervical cancer, cervical intraepithelial neoplasia, and genital warts. The two strategies used were 1) current practice and 2) prophylactic quadrivalent vaccine against HPV types 6, 11, 16, and 18. We developed a Markov simulation model to evaluate the incremental cost-effectiveness ratio of prophylactic HPV vaccine. Women transition through a model either healthy or developing HPV or its related diseases, or die from cervical cancer or from other causes according to transitional probabilities under the Thai health-care context. Costs from a provider perspective were obtained from King Chulalongkorn Memorial Hospital. Costs and benefits were discounted at 3% annually. Compared with no prophylactic HPV vaccine, the incremental cost-effectiveness ratio was 160,649.50 baht per quality-adjusted life-year. The mortality rate was reduced by 54.8%. The incidence of cervical cancer, cervical intraepithelial neoplasia grade 1, cervical intraepithelial neoplasia grade 2/3, and genital warts was reduced by up to 55.1%. Compared with commonly accepted standard thresholds recommended by the World Health Organization Commission on Macroeconomics and Health, the nationwide coverage of HPV vaccination in girls is likely to be cost-effective in Thailand. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Supporting transitions in medical career pathways: the role of simulation-based education.

Science.gov (United States)

Cleland, Jennifer; Patey, Rona; Thomas, Ian; Walker, Kenneth; O'Connor, Paul; Russ, Stephanie

2016-01-01

Transitions, or periods of change, in medical career pathways can be challenging episodes, requiring the transitioning clinician to take on new roles and responsibilities, adapt to new cultural dynamics, change behaviour patterns, and successfully manage uncertainty. These intensive learning periods present risks to patient safety. Simulation-based education (SBE) is a pedagogic approach that allows clinicians to practise their technical and non-technical skills in a safe environment to increase preparedness for practice. In this commentary, we present the potential uses, strengths, and limitations of SBE for supporting transitions across medical career pathways, discussing educational utility, outcome and process evaluation, and cost and value, and introduce a new perspective on considering the gains from SBE. We provide case-study examples of the application of SBE to illustrate these points and stimulate discussion.

Novel paradigm for immunotherapy of ovarian cancer by engaging prophylactic immunity against hepatitis B virus.

Science.gov (United States)

Malecki, Marek; Putzer, Emily; Quach, Caroline; Dodivenaka, Chaitanya; Tombokan, Xenia

2016-12-01

Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective. The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination-induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy. Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients' informed consent. By biomolecular engineering, we have created a novel family of biomolecules: antibody × vaccine engineered constructs (AVEC: anti-HER-2 × HBsAg). We have collected the blood from the volunteers, and measured the titers of anti-HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER-2 over-expressing epithelial ovarian cancers: OV-90, TOC-112D, SKOV-3, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER-2+ ovarian cancer cells with AVEC: anti-HER-2 × HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti-HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti-HER-2 antibodies alone and/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE

The fellow eye in patients with unilateral retinal detachment: findings and prophylactic treatment.

Science.gov (United States)

Laatikainen, L

1985-10-01

During a 4-year period, 1978-1981, 312 patients were operated on for unilateral rhegmatogenous detachment of the retina. Of the fellow eyes, 11% showed moderate (VA 0.15-0.4) and 5% severe (VA less than or equal to 0.1) visual impairment. Of the fellow eyes 49% were myopic (- 1.0 D. or more), and aphakia was present in 14%. Details of the peripheral fundus were adequately recordable for 260 fellow eyes. Degenerations considered to predispose to retinal detachment were found in 98 eyes (38%): lattice degeneration in 54 (21%), granular tuft in 17 (7%), retinal tear(s) in 12 (5%), and retinoschisis in 15 (6%). Prophylactic treatment of predisposing degenerations was performed in 91 of the 98 eyes using cryo- or photocoagulation (argon laser). No intra- or permanent post-operative complications were noticed. One of the treated fellow eyes (1.1%) detached 10 months after prophylactic treatment due to new tears. In the untreated group, 6 of the 221 eyes detached (2.7%). The difference was not statistically significant, but the groups were not comparable because 93% of the eyes showing predisposing degenerations were treated. None of the eyes treated for retinal breaks or lattice degeneration has detached. In these cases prophylactic treatment of the fellow eye is recommended. In most eyes cryocoagulation seems to be preferable to photocoagulation.

In patients with a tumour invading the phrenic nerve does prophylactic diaphragm plication improve postoperative lung function?

Science.gov (United States)

Beattie, Gwyn W; Dunn, William G; Asif, Mohammed

2016-09-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients with tumours involving the phrenic nerve, does prophylactic diaphragm plication improve lung function following tumour resection?' Using the reported search, 258 papers were found of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Three case reports and one case series represent 37 patients in the literature along with two relevant animal studies. Patients treated with prophylactic plication at the time of injury or sacrifice of the phrenic nerve had reduced radiological evidence of diaphragm paralysis, lower reported shortness of breath and reduced requirement for ventilatory support. In patients with prophylactic diaphragm plication and a concurrent pulmonary resection, the predicted postoperative lung function correlated closely with the postoperative measured FEV1, FVC and gas transfer. The postoperative measured FEV1 was reported as 86-98%, the FVC 82-89% and gas transfer 97% of the predicted values. Two animal models investigate the mechanics of respiration, spirometry and gas exchange following diaphragmatic plication. A randomized control study in four dogs measured a 50% reduction in tidal volume and respiratory rate, a 40% decrease in arterial PO2 and a 43% increase in arterial CO2 when the phrenic nerve was crushed in animals with a pneumonectomy but without prophylactic diaphragm plication. A further randomized control animal study with 28 dogs found that plicating the diaphragm after unilateral phrenic nerve transection resulted in a significant increase in tidal volume and lung compliance and a significant decrease in respiratory frequency and the work of breathing. Prophylactic diaphragm plication may preserve lung function, reduce the risk of

Prophylactic post-operative radiotherapy prevents heterotopic ossification following traumatic acetabular fracture

International Nuclear Information System (INIS)

Meyer, Joseph T.; Hixson, William C.; Jennelle, Richard L. S.; Alonso, Jorge E.; Raben, David; Spencer, Sharon S.; Kim, Robert Y.

1996-01-01

Purpose/Objective: To determine the effect of post-operative radiation on the incidence of heterotopic ossification following traumatic acetabular fracture. Materials and Methods: A retrospective analysis was performed of the medical records and radiographs of all patients who received prophylactic radiotherapy to prevent heterotopic ossification. These results were compared to a similar group of patients receiving no prophylactic radiotherapy following traumatic acetabular fracture. Between 1987 and 1994, sixty-six patients received prophylactic radiotherapy to prevent heterotopic ossification. Results: Thirty-six patients (55%) received radiotherapy following operative repair of a traumatic acetabular fracture (median follow-up: 210 days). Three dose schedules were utilized: (28(36)) (77.8%) received 700 cGy/1 fx, (2(36)) (5.5%) 800 cGy/1 fx, and (6(36)) (16.7%) 1000 cGy/5 fxs. These patients were retrospectively compared with thirty-four patients who received similar operative management of traumatic acetabular fractures without post-operative radiotherapy (median follow-up: 378 days). Of the patients with heterotopic ossification, 96% developed it within 180 days. Complications and delayed wound healing rates were not significantly different in patients treated with or without post-operative radiotherapy, 6.4% and 6.3% respectively (p=0.49). The incidence of heterotopic ossification at last follow-up in patients treated with and without post-operative radiotherapy was (5(36)) (13.9%) and (19(34)) (55.9%), respectively (p=0.000332). For all patients, type of surgical approach was associated with development of heterotopic ossification: posterior, (7(38)) (18.4%), ilio-inguinal (1(3)) (33.3%), tri-radiate (13(19)) (68.4%), p=.000511. In patients receiving post-operative radiotherapy, variables associated with heterotopic ossification included dose (p=.00962), injury-to-radiation interval (p=.0038), and surgery-to-radiation interval (p=.0238). Fifty percent ((3

Nursing Informatics Certification Worldwide: History, Pathway, Roles, and Motivation

Science.gov (United States)

Cummins, M. R.; Gundlapalli, A. V.; Murray, P.; Park, H.-A.; Lehmann, C. U.

2016-01-01

Summary Introduction Official recognition and certification for informatics professionals are essential aspects of workforce development. Objective: To describe the history, pathways, and nuances of certification in nursing informatics across the globe; compare and contrast those with board certification in clinical informatics for physicians. Methods (1) A review of the representative literature on informatics certification and related competencies for nurses and physicians, and relevant websites for nursing informatics associations and societies worldwide; (2) similarities and differences between certification processes for nurses and physicians, and (3) perspectives on roles for nursing informatics professionals in healthcare Results The literature search for ‘nursing informatics certification’ yielded few results in PubMed; Google Scholar yielded a large number of citations that extended to magazines and other non-peer reviewed sources. Worldwide, there are several nursing informatics associations, societies, and workgroups dedicated to nursing informatics associated with medical/health informatics societies. A formal certification program for nursing informatics appears to be available only in the United States. This certification was established in 1992, in concert with the formation and definition of nursing informatics as a specialty practice of nursing by the American Nurses Association. Although informatics is inherently interprofessional, certification pathways for nurses and physicians have developed separately, following long-standing professional structures, training, and pathways aligned with clinical licensure and direct patient care. There is substantial similarity with regard to the skills and competencies required for nurses and physicians to obtain informatics certification in their respective fields. Nurses may apply for and complete a certification examination if they have experience in the field, regardless of formal training. Increasing

Prophylactic Fasciotomy in a Porcine Model of Extremity Trauma

Science.gov (United States)

2014-07-16

Morrison, MRCS,b,c,d Jerry R. Spencer, BS,a James D. Ross, PhD,a and Todd E. Rasmussen, MD, FACSa,e,f,* a59th Medical Wing, Joint Base San Antonio, San...Vascular injury Extremity Ischemiaereperfusion Recovery Neuromuscular Functional Fasciotomy a b s t r a c t Background: Extremity injury, with...prophylactic fasciotomy on neuromuscular recovery, labora- tory markers of ischemiaereperfusion, and tissue injury as determined by histologic evaluation. We

The strategy of performing non-prophylactic hemodialysis therapy after administration of contrast media in renal insufficiency patients

International Nuclear Information System (INIS)

Hokama, Sanehiro; Oda, Masami; Kadekawa, Katsumi

2007-01-01

Acute renal failure induced by contrast media is an important problem in renal insufficiency patients. Prophylactic hemodialysis is usually undertaken after the administration of radiocontrast media. However, we decided to cease giving prophylactic hemodialysis from February, 2002 in line with the guidelines regarding dialysis and contrast media administration provided by the European Society of Urogenital Radiology. We reported our policy at the doctor's meeting of hemodialysis therapy and at the meeting of clinical engineering technologists which were held in Okinawa. After the presentation, a questionnaire survey in 28 hospitals was undertaken by telephone. In all the hospitals, prophylactic hemodialysis after the administration of radiocontrast media was still being continued, with the exception of one hospital. We need to enlighten medical staff that the strategy of performing hemodialysis immediately after the administration of contrast media in patients with reduced renal function does not diminish the rate of radiocontrast media-induced nephropathy. (author)

Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity

OpenAIRE

Kant, Shashi; Barrett, Tamera; Vertii, Anastassiia; Noh, Yun Hee; Jung, Dae Young; Kim, Jason K.; Davis, Roger J.

2013-01-01

Saturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that l...

Prophylactic iodine treatment in radiation protection

International Nuclear Information System (INIS)

Oberhausen, E.

1980-01-01

Prophylactic iodine treatment is to prevent accumulation of radioactive iodine in the thyroid. This is done by administering a large amount of stable iodine before uptake of radioactive iodine so that further accummulation of iodine in the thyroid will be impossible. This blocking effect should be as complete as possible. This is achieved by administering an initial dose of 200 mg potassium iodide. As the release of radioactive iodine may last several hours or even days; for this reason, maintenance doses of 100 mg potassium iodide should be administered in 8-hour intervals. The risk of prophylactiv iodine treatment is rather low; however, provocation of latent hyperthyreoses must be expected in, at the most, 0.2% of the exposed population. (orig./MG) [de

Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy -- an MR analysis

International Nuclear Information System (INIS)

Matsumoto, Ko; Takahashi, Shoki; Sato, Atsushi; Imaizumi, Masue; Higano, Shuichi; Sakamoto, Kiyohiko; Asakawa, Hiroshi; Tada, Keiya

1995-01-01

Purpose: The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. Methods and Materials: Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients' age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature review. Results: Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. Conclusion: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient's age and CRT dose

Guidelines on the use of stable iodine as a prophylactic measure during nuclear emergencies

International Nuclear Information System (INIS)

1995-09-01

Among the fission products that may be released in a power reactor accident the radio iodines are unique in that the dose received by persons exposed by inhalation of radio iodines in the gaseous plume may be substantially reduced. GMA-9 provides guidance on the medical aspects of the use of stable iodine compounds as a prophylactic measure in the event of a nuclear accident. A review of the physiologic basis for the use of stable iodine as a prophylactic measure and the effects of radiation on the thyroid gland are provided. Logistic factors that must be considered to provide the optimum level of radiological protection and medical safety are also addressed. 71 refs., 6 tabs., 2 figs

Guidelines on the use of stable iodine as a prophylactic measure during nuclear emergencies

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-09-01

Among the fission products that may be released in a power reactor accident the radio iodines are unique in that the dose received by persons exposed by inhalation of radio iodines in the gaseous plume may be substantially reduced. GMA-9 provides guidance on the medical aspects of the use of stable iodine compounds as a prophylactic measure in the event of a nuclear accident. A review of the physiologic basis for the use of stable iodine as a prophylactic measure and the effects of radiation on the thyroid gland are provided. Logistic factors that must be considered to provide the optimum level of radiological protection and medical safety are also addressed. 71 refs., 6 tabs., 2 figs.

Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval.

Science.gov (United States)

Xu, Chun; Krabbe, Sabine; Gründemann, Jan; Botta, Paolo; Fadok, Jonathan P; Osakada, Fumitaka; Saur, Dieter; Grewe, Benjamin F; Schnitzer, Mark J; Callaway, Edward M; Lüthi, Andreas

2016-11-03

Memories about sensory experiences are tightly linked to the context in which they were formed. Memory contextualization is fundamental for the selection of appropriate behavioral reactions needed for survival, yet the underlying neuronal circuits are poorly understood. By combining trans-synaptic viral tracing and optogenetic manipulation, we found that the ventral hippocampus (vHC) and the amygdala, two key brain structures encoding context and emotional experiences, interact via multiple parallel pathways. A projection from the vHC to the basal amygdala mediates fear behavior elicited by a conditioned context, whereas a parallel projection from a distinct subset of vHC neurons onto midbrain-projecting neurons in the central amygdala is necessary for context-dependent retrieval of cued fear memories. Our findings demonstrate that two fundamentally distinct roles of context in fear memory retrieval are processed by distinct vHC output pathways, thereby allowing for the formation of robust contextual fear memories while preserving context-dependent behavioral flexibility. Copyright © 2016 Elsevier Inc. All rights reserved.

Prophylactic ampicillin versus cefazolin for the prevention of post-cesarean infectious morbidity in Rwanda.

Science.gov (United States)

Mivumbi, Victor N; Little, Sarah E; Rulisa, Stephen; Greenberg, James A

2014-03-01

To evaluate the efficacy of ampicillin versus cefazolin as prophylactic antibiotics prior to cesarean delivery in Rwanda. In a prospective, randomized, open-label, single-site study conducted between March and May 2012, the effects of prophylactic ampicillin versus cefazolin were compared among women undergoing cesarean delivery at the Centre Hospitalier Universitaire de Kigali, Rwanda. Postoperatively, participants were evaluated daily for infectious morbidity while in the hospital. Follow-up was done by phone and by appointment at the hospital within 2 weeks of delivery. During the study period, there were 578 total deliveries and 234 cesarean deliveries (40.4%). Overall, 132 women were enrolled in the study and randomized to receive either ampicillin (n=66) or cefazolin (n=66). No women were lost to follow-up. The overall infection rate was 15.9% (21/132). The infection rate in the ampicillin group and the cefazolin group was 25.8% (17/66) and 6.1% (4/66), respectively. Implementing a universal protocol in Rwanda of prophylactic cefazolin prior to cesarean delivery might reduce postoperative febrile morbidity, use of postoperative antibiotics, and number of postoperative days in hospital. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Prophylactic intracameral vancomycin: efficacy in preventing endophthalmitis after cataract surgery

Directory of Open Access Journals (Sweden)

Manash Kumar Goswami

2016-01-01

Full Text Available Background and objective: Post Operative endophthalmitis is rare but devastating complication in ocular surgery. The present study determined the efficacy of intracameral vancomycin after phaco-emusification cataract surgery to prevent endophthalmitis. Method: A total of 768 cases who had undergone phaco-emusification cataract surgery were included in the study. Every alternate patient received 0.5 ml injection of vancomycin (1mg in 0.1 ml in the anterior chamber after completion of phaco-emulcification and formation of anterior chamber. All the patients were examined for symptoms and signs of bacterial endophthalmitis at 24 hrs, 7 days, 15 days and subsequently at 1, 3 and 6 months following surgery. Results: No endophthalmitis case was recorded at any time period during 6 month follow up in either group. However, significantly higher number of cases in vancomycin group had cells in anterior chamber and disturbances in visual acuity at day 15 following surgery. Conclusion: Vancomycin did not have any prophylactic role in preventing endophthalmitis. Proper aseptic measures are important to prevent any infection in ocular surgery. IMC J Med Sci 2016; 10(1: 24-28

Medium-dose riboflavin as a prophylactic agent in children with migraine: A preliminary placebo-controlled, randomised, double-blind, cross-over trial

NARCIS (Netherlands)

J.K.J. Bruijn (Jacques); H.J. Duivenvoorden (Hugo); J. Passchier (Jan); H. Locher (Heiko); N. Dijkstra (Natascha); W.F.M. Arts (Willem Frans)

2010-01-01

textabstractBackground: Riboflavin seems to have a promising effect on migraine in adults. The present study examines whether riboflavin has a prophylactic effect on migraine in children. Objective: To investigate whether riboflavin in a dosage of 50 mg/day has a prophylactic effect on migraine

Potential Harm of Prophylactic Platelet Transfusion in Adult Dengue Patients.

Science.gov (United States)

Lee, Tau-Hong; Wong, Joshua G X; Leo, Yee-Sin; Thein, Tun-Linn; Ng, Ee-Ling; Lee, Linda K; Lye, David C

2016-03-01

Thrombocytopenia is a hallmark of dengue infection, and bleeding is a dreaded complication of dengue fever. Prophylactic platelet transfusion has been used to prevent bleeding in the management of dengue fever, although the evidence for its benefit is lacking. In adult dengue patients with platelet count Tan Tock Seng Hospital from January 2005 to December 2008. Baseline characteristics and clinical outcomes were compared between the non-transfused vs. transfused groups. Outcomes studied were clinical bleeding, platelet increment, hospital length of stay, intensive care unit admission and death. Of the 788 patients included, 486 received prophylactic platelet transfusion. There was no significant difference in the presence of clinical bleeding in the two groups (18.2% in non-transfused group vs. 23.5% in transfused group; P = 0.08). Patients in the transfused group took a median of 1 day longer than the non-transfused group to increase their platelet count to 50,000/mm3 or more (3 days vs. 2 days, P hospital stay in the non-transfused group was 5 days vs. 6 days in the transfused group (P50,000/mm3 and increasing length of hospitalization.

Prophylactic transcervical amnioinfusion in laboring women with oligohydramnios.

Science.gov (United States)

Amin, A F; Mohammed, M S; Sayed, G H; Abdel-Razik, S

2003-05-01

Evaluation of prophylactic intrapartum amnioinfusion in women with oligohydramnios. Assiut University Hospital during the period from February 2000 to September 2001, 160 laboring women with oligohydramnios [amniotic fluid index (AFI) amnioinfusion and control groups. Inclusion criteria were: term singleton gestation, vertex presentation, cervical dilatation amnioinfusion was done with warmed normal saline. there was a significant increase in AFI after amnioinfusion (Pamnioinfusion group showed lower cesarean section rate for fetal distress (P=0.003), lower incidence of abnormal FHR (P=0.006), fewer neonates with Apgar score amnioinfusion is a simple, safe and effective procedure.

Visual-Cerebellar Pathways and Their Roles in the Control of Avian Flight

Directory of Open Access Journals (Sweden)

Douglas R. Wylie

2018-04-01

Full Text Available In this paper, we review the connections and physiology of visual pathways to the cerebellum in birds and consider their role in flight. We emphasize that there are two visual pathways to the cerebellum. One is to the vestibulocerebellum (folia IXcd and X that originates from two retinal-recipient nuclei that process optic flow: the nucleus of the basal optic root (nBOR and the pretectal nucleus lentiformis mesencephali (LM. The second is to the oculomotor cerebellum (folia VI-VIII, which receives optic flow information, mainly from LM, but also local visual motion information from the optic tectum, and other visual information from the ventral lateral geniculate nucleus (Glv. The tectum, LM and Glv are all intimately connected with the pontine nuclei, which also project to the oculomotor cerebellum. We believe this rich integration of visual information in the cerebellum is important for analyzing motion parallax that occurs during flight. Finally, we extend upon a suggestion by Ibbotson (2017 that the hypertrophy that is observed in LM in hummingbirds might be due to an increase in the processing demands associated with the pathway to the oculomotor cerebellum as they fly through a cluttered environment while feeding.

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

Directory of Open Access Journals (Sweden)

Nandini D.P.K. Manne

2017-07-01

Full Text Available Background: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS are responsible for hepatic IR injury. Cerium oxide (CeO2 nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. Methods: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR group and hepatic ischemia reperfusion (IR plus CeO2 nanoparticle group (IR+ CeO2. Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Results: Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Conclusion: Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic

Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial

NARCIS (Netherlands)

de Bruijn, J; Duivenvoorden, H.J.; Passchier, J.; Locher, H.; Dijkstra, N.; Arts, W.F.

2010-01-01

Background: Riboflavin seems to have a promising effect on migraine in adults. The present study examines whether riboflavin has a prophylactic effect on migraine in children. Objective: To investigate whether riboflavin in a dosage of 50 mg/day has a prophylactic effect on migraine attacks in young

Roles of Chaperone/Usher Pathways of Yersinia pestis in a Murine Model of Plague and Adhesion to Host Cells

Science.gov (United States)

Hatkoff, Matthew; Runco, Lisa M.; Pujol, Celine; Jayatilaka, Indralatha; Furie, Martha B.; Bliska, James B.

2012-01-01

Yersinia pestis and many other Gram-negative pathogenic bacteria use the chaperone/usher (CU) pathway to assemble virulence-associated surface fibers termed pili or fimbriae. Y. pestis has two well-characterized CU pathways: the caf genes coding for the F1 capsule and the psa genes coding for the pH 6 antigen. The Y. pestis genome contains additional CU pathways that are capable of assembling pilus fibers, but the roles of these pathways in the pathogenesis of plague are not understood. We constructed deletion mutations in the usher genes for six of the additional Y. pestis CU pathways. The wild-type (WT) and usher deletion strains were compared in the murine bubonic (subcutaneous) and pneumonic (intranasal) plague infection models. Y. pestis strains containing deletions in CU pathways y0348-0352, y1858-1862, and y1869-1873 were attenuated for virulence compared to the WT strain by the intranasal, but not subcutaneous, routes of infection, suggesting specific roles for these pathways during pneumonic plague. We examined binding of the Y. pestis WT and usher deletion strains to A549 human lung epithelial cells, HEp-2 human cervical epithelial cells, and primary human and murine macrophages. Y. pestis CU pathways y0348-0352 and y1858-1862 were found to contribute to adhesion to all host cells tested, whereas pathway y1869-1873 was specific for binding to macrophages. The correlation between the virulence attenuation and host cell binding phenotypes of the usher deletion mutants identifies three of the additional CU pathways of Y. pestis as mediating interactions with host cells that are important for the pathogenesis of plague. PMID:22851745

Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity.

Science.gov (United States)

Ekman, Matthias; Fiebach, Christian J; Melzer, Corina; Tittgemeyer, Marc; Derrfuss, Jan

2016-03-09

The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs considerably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. In contrast, in Study 2, where participants were required to maintain working memory items without updating, only the connectivity of the direct pathway was predictive of individual WMC. Our results suggest an important dissociation in the circuitry connecting frontal and parietal regions, where direct frontoparietal connections might support storage and maintenance, whereas subcortically mediated connections support the flexible updating of working memory content. Copyright © 2016 the authors 0270-6474/16/362894-10$15.00/0.

Prophylactic fenbendazole therapy does not affect the incidence and onset of type 1 diabetes in non-obese diabetic mice.

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Franke, Deanna D H; Shirwan, Haval

2006-03-01

Fenbendazole (FBZ) is a common, highly efficacious broad-spectrum anthelmintic drug used to treat and limit rodent pinworm infections. However, the effect of its prophylactic use on the immune response of rodents is largely undefined. The non-obese diabetic (NOD) mouse is a model commonly used to study type 1 diabetes (T1D). Parasitic infections will inhibit diabetes development in NOD mice; thus, in the presence of contamination, prophylactic treatment with anthelmintics must be considered to maintain experimental research. Herein, we investigated the prophylactic use of FBZ in NOD mice to determine its effect on the incidence and onset of diabetes, lymphocyte sub-populations and T cell proliferative responses. NOD mice were separated into control and treatment groups. The treatment group received a diet containing FBZ. Animals were monitored for the incidence and onset of T1D. At matched time points, diabetic and non-diabetic mice were killed and splenic lymphocytes analyzed for various cell sub-populations and mitogen-induced proliferative responses using flow cytometry. Treated and control mice were monitored >23 weeks with no detectable effects on the incidence or onset of diabetes. Moreover, no significant differences were detected in lymphocyte sub-populations and mitogen-induced CD4(+) and CD8(+) proliferative responses between control and treatment groups. These results suggest that prophylactic FBZ treatment does not significantly alter the incidence or onset of diabetes in NOD mice. The prophylactic use of FBZ, therefore, presents a viable approach for the prevention of pinworm infection in precious experimental animals with substantial scientific and economic benefits.

Prophylactic antibiotics for penetrating abdominal trauma.

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Brand, Martin; Grieve, Andrew

2013-11-18

Penetrating abdominal trauma occurs when the peritoneal cavity is breached. Routine laparotomy for penetrating abdominal injuries began in the 1800s, with antibiotics first being used in World War II to combat septic complications associated with these injuries. This practice was marked with a reduction in sepsis-related mortality and morbidity. Whether prophylactic antibiotics are required in the prevention of infective complications following penetrating abdominal trauma is controversial, however, as no randomised placebo controlled trials have been published to date. There has also been debate about the timing of antibiotic prophylaxis. In 1972 Fullen noted a 7% to 11% post-surgical infection rate with pre-operative antibiotics, a 33% to 57% infection rate with intra-operative antibiotic administration and 30% to 70% infection rate with only post-operative antibiotic administration. Current guidelines state there is sufficient class I evidence to support the use of a single pre-operative broad spectrum antibiotic dose, with aerobic and anaerobic cover, and continuation (up to 24 hours) only in the event of a hollow viscus perforation found at exploratory laparotomy. To assess the benefits and harms of prophylactic antibiotics administered for penetrating abdominal injuries for the reduction of the incidence of septic complications, such as septicaemia, intra-abdominal abscesses and wound infections. Searches were not restricted by date, language or publication status. We searched the following electronic databases: the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2013, issue 12 of 12), MEDLINE (OvidSP), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) and PubMed. Searches were last conducted in January 2013. All randomised controlled trials of antibiotic prophylaxis in patients with penetrating abdominal trauma versus no

[Prophylactic treatment of retinal detachment].

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Binder, S; Riss, B

1981-08-01

The indications for and results of prophylactic treatment of retinal detachment during a period of five years are reported and compared with the results in the literature. Half of the cases (3 out of 6 eyes) which developed a retinal detachment had been horse-shoe tears combined with a vitreous hemorrhage. For this reason a small buckle operation is recommended in these cases, to prevent further traction. Lattice degeneration should rather be observed than treated, except in special cases: This includes eyes where the fellow eye had a detachment from a lattice degeneration, cases in which one eye is blind from an uncured detachment or has no useful visual acuity, and eyes whose fellow eye has giant tears. In aphakic eyes treatment of lattice degeneration is recommended, because the incidence of detachment from these areas is high, especially in young aphakic cases. In one aphakic eye which had been photocoagulated several times the formation of a preretinal membrane was observed.

Retroperitoneal Bleeding: An Experience During Prophylactic Anticoagulation in a Patient With Nephrotic Syndrome

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Mari Okada

2017-07-01

Full Text Available The association between nephrotic syndrome (NS and a hypercoagulable state has been demonstrated. Controlling the blood clotting activity may therefore be attractive for patients with nephrosis in terms of thromboembolism prophylaxis. We herein report a 75-year-old woman with minimal change disease who developed pains in the right back, groin, and thigh because of retroperitoneal bleeding during prophylactic anticoagulation with unfractionated heparin. Although this procedure has not been accepted as the standard of care for patients with nephrosis, pharmacologic prophylaxis may already be practiced empirically, as in the present patient. We believe that our experience highlights the pitfalls of such a management in patients with nephrosis, implying the need for a diagnostic strategy for identifying those patients with NS who can benefit from prophylactic anticoagulation. Several concerns that emerged in this case are also discussed.

Exploring the future role of Asia utilizing a Scenario Matrix Architecture and Shared Socio-economic Pathways

International Nuclear Information System (INIS)

Eom, Jiyong; Calvin, Kate; Clarke, Leon; Edmonds, Jae; Kim, Sonny; Kopp, Robert; Kyle, Page; Luckow, Patrick; Moss, Richard; Patel, Pralit; Wise, Marshall

2012-01-01

We explore the implications that alternative pathways for human population and economic development have for the role of Asia in reference no-climate-policy scenarios and scenarios in which climate forcing is limited. We consider three different pathways of socioeconomic development, which we refer to as Shared Socio-economic Pathways (SSPs) and four different levels of limitation on climate forcing, which we refer to as Shared Climate Policy Assumptions (SPAs). SSPs are differentiated by population and economic growth assumptions, while SPAs are differentiated on the level of radiative forcing in the year 2100. Regardless of the scenarios we examined Asia plays a central role in shaping the world's future with nearly half of the world's people and more than half of the world's economic activity and energy consumption. The future of Asia and the world are dramatically different across the various combinations of SSPs and SPAs. High population worlds place significant stress on Asian resources and ecosystems. In high population SSPs the poorest members of the population face high energy and food prices and the more stringent the level of emissions mitigation, the more stress poor populations experience, though the more stringent the emissions mitigation, the larger the area of unmanaged ecosystems that are preserved. - Highlights: ► We explore the implications of alternative population and economic pathways for the role of Asia. ► High population world places significant stress on Asian resources and ecosystems. ► In high population world, the poorest members of the population face high energy and food prices. ► The greater level of emissions mitigation, the more stress poor people experience. ► The greater the emissions mitigation, the larger the area of unmanaged ecosystems preserved.

The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms

DEFF Research Database (Denmark)

Voigt Hansen, Melissa; Danielsen, A K; Hageman, I

2014-01-01

Circadian- and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. The effect of melatonin on depression/depressive symptoms has been investigated previously. This systematic review assesses the current evidence of a therapeutic- and prophylactic e...

Efficacy of prophylactic splenectomy for proximal advanced gastric cancer invading greater curvature.

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Ohkura, Yu; Haruta, Shusuke; Shindoh, Junichi; Tanaka, Tsuyoshi; Ueno, Masaki; Udagawa, Harushi

2017-05-25

For proximal gastric cancer invading the greater curvature, concomitant splenectomy is frequently performed to secure the clearance of lymph node metastases. However, prognostic impact of prophylactic splenectomy remains unclear. The aim of this study was to clarify the oncological significance of prophylactic splenectomy for advanced proximal gastric cancer invading the greater curvature. Retrospective review of 108 patients who underwent total or subtotal gastrectomy for advanced proximal gastric cancer involving the greater curvature was performed. Short-term and long-term outcomes were compared between the patients who underwent splenectomy (n = 63) and those who did not (n = 45). Patients who underwent splenectomy showed higher amount of blood loss (538 vs. 450 mL, p = 0.016) and morbidity rate (30.2 vs. 13.3, p = 0.041) compared with those who did not undergo splenectomy. In particular, pancreas-related complications were frequently observed among patients who received splenectomy (17.4 vs. 0%, p = 0.003). However, no significant improvement of long-term outcomes were confirmed in the cases with splenectomy (5-year recurrence-free rate, 60.2 vs. 67.3%; p = 0.609 and 5-year overall survival rates, 63.7 vs. 73.6%; p = 0.769). On the other hand, splenectomy was correlated with marginally better survival in patients with Borrmann type 1 or 2 gastric cancer (p = 0.072). For advanced proximal gastric cancer involving the greater curvature, prophylactic splenectomy may have no significant prognostic impact despite the increased morbidity rate after surgery. Such surgical procedure should be avoided as long as lymph node involvement is not evident.

Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau.

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Garly, May-Lill; Balé, Carlitos; Martins, Cesário Lourenco; Whittle, Hilton C; Nielsen, Jens; Lisse, Ida M; Aaby, Peter

2006-12-16

To investigate whether prophylactic antibiotics can prevent complications of measles. Community based, randomised, double blind, placebo controlled trial. Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa. 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war). Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days. Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media. The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups. The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries. Clinical trials NCT00168532.

Prophylactic Antiviral Treatment in Recurrent Herpes Zoster: A Case Report

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Hatice Gamze Bayram

2011-06-01

Full Text Available Herpes zoster (HZ occurs in older ages with activation of varicella-zoster virus (VZV which persists in a dormant phase within the dorsal root ganglia. The incidence of HZ in immunosuppressed patients is 20-100 times higher and the clinical progress is more severe than in immunocompetent individuals. A 48-year-old man who had been diagnosed with acute myelocytic leukemia type M3 and had been treated with immunosuppressive agents was admitted to our clinic. The patient was clinically diagnosed as having HZ. He was treated with acyclovir 800 mg five times daily for 7 days. In the consecutive three months, he attended our clinic again with similar complaints. The left cervical (C5, C6 dermatomes were involved at the fourth attack of HZ. Multinucleated giant cells were determined on the Tzanck smear. VZV DNA was detected by polymerase chain reaction (PCR. Treatment with valacyclovir 1 g three times daily for 14 days was prescribed and then, prophylactic treatment with valacyclovir 500 mg two times a day was administered. Although immunosuppressive treatment was continued, no new attacks of herpes zoster occurred. We think that prophylactic antiviral therapy should be initiated in immunosuppressive individuals who have recurrent herpes zoster attacks.

Relish2 mediates bursicon homodimer-induced prophylactic immunity in the mosquito Aedes aegypti

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Bursicon is a neuropeptide hormone consisting of two cystine-knot proteins (burs a and burs ß), responsible for cuticle tanning and other developmental processes in insects. Recent studies show that each bursicon subunit forms homodimers that induce prophylactic immunity in Drosophila melanogaster. ...

The therapeutic and prophylactic role of oral zinc sulfate in management of recurrent aphthous stomatitis ras in comparison with dapsone

International Nuclear Information System (INIS)

Sharique, Khalifa E.; Najim, Rafid A.; Al-Nuaimy, Adil A.; Al-Hayani, Raafa K.; Maroof, Darseem M.

2008-01-01

Objective was to evaluate the therapeutic and prophylactic effectiveness of oral zinc sulfate in recurrent aphthous stomatitis RAS in comparison with dapsone. A double-blind placebo controlled study, conducted in the Department of Dermatology, Baghdad Teaching Hospitals, Baghdad, Iraq between May 2005 and October 2006, in which 45 patents with RAS were recruited and divided into 3 equal groups: group A on zinc sulfate 150 mg twice daily, group B on dapsone 50 mg twice daily and group C on glucose 250 mg as placebo. The drugs were prepared in identical capsules and patents were instructed to take the capsules twice daily after meals in a double blind manner. Assessment of each patient was carried out by the Oral Clinical Manifestation Index OCMI and the diameter of the ulcers at day 0, day 4 and the second, fourth, sixth, eighth, tenth and twelfth weeks of the therapy. Forty-five patients were included in the study 25 males and 20 females and their ages ranged between 16-45 years mean +/-SD 31.24+/-8.14. In group A, the mean of OCMI and diameters of the ulcers improved, with a p=0.0001 for OCMI, and 0.0001 for the diameter for ulcers at the end of the twelfth week of therapy, which was statistically significant. Group B also showed significant improvement, however, the action was lower and slower p=0.0001 for OCMI and 0.001 for the diameter for ulcers. Group C revealed slight non-significant improvement p=0.028 for OCMI and 0.034 for the diameter of ulcers. In the sixth week of therapy, zinc sulfate was more effective than dapsone in reducing in reducing the reducing the OCMI of the ulcers p=0.007. The present study showed that both zinc sulfate and dapsone had significant therapeutic and prophylactic affects in controlling RAS, however, zinc sulfate had much more rapid and sustained action. (author)

The Efficacy of Postoperative Prophylactic Antibiotics in Orthognathic Surgery: A Prospective Study in Le Fort I Osteotomy and Bilateral Intraoral Vertical Ramus Osteotomy

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Kang, Sang-Hoon; Yoo, Jae-Ha

2009-01-01

Purpose This study examined the efficacy of the postoperative prophylactic antibiotics used in orthognathic surgery. The prevalence of surgical site infections (SSIs) was determined according to the use of postoperative prophylactic antibiotics. Patients and Methods Fifty-six patients were divided into 2 groups. Each patient intravenously received 1.0 g of a third-generation cephalosporin (Cefpiramide) 30 minutes before surgery. Among them, 28 patients in the control group received 1.0 g Cefpiramide twice daily until the third day after surgery. The postoperative wounds were examined regularly for the presence of infectious signs. Results There was no significant difference in the incidence of postoperative wound infections between patients who had received postoperative prophylactic antibiotic administration and those who had not (p = 0.639). Conclusion Prolonged prophylactic antibiotic use after orthognathic surgery may not be necessary, provided that there are no other significant factors for wound infections. PMID:19259349

Barriers and motivators of adherence to prophylactic treatment in haemophilia : a systematic review

NARCIS (Netherlands)

Schrijvers, L. H.; Uitslager, N.; Schuurmans, M. J.; Fischer, K.

Long-term adherence to prophylactic therapy is the key to successful prevention of bleeds in severe haemophilia. The present study aims to provide a systematic review of the literature on the determinants of adherence to prophylaxis in haemophilia. A literature search in the largest medical

Evaluation of prophylactic antibiotic administration in general surgery division of a teaching hospital in north of Iran

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Paniz Yousefi

2016-01-01

Full Text Available Surgical site infections are one of the most important post-surgery complications. Antimicrobial prophylaxis has been used routinely in surgeries to reduce infection incidence. However, inappropriate selection of antimicrobial agents or dosing can develop antimicrobial resistance, serious adverse reactions and prolong hospitalization. Current study aimed to examine prophylactic antibiotic prescription in surgeries in a teaching hospital in Sari, Mazandaran and evaluate level of adherence to the international guidelines. Between January 2015 to May 2015, 104 patients in general surgery ward were selected and enrolled in the study. The prophylactic antibiotics, dosage, timing and duration of administration were collected by reviewing patients’ records and compared to the existing guidelines. Prophylactic antibiotic was given to 85.5% of patients. Prescribed antibiotics were cefazolin (46.1%, metronidazole (24%, ceftriaxone (12.5%, ciprofloxacin (1.9% and vancomycin (0.96%. Most of the patients (62.9% received an inappropriate and delayed timing. Proper antibiotic dosage was seen in 45.2% of patients. All patients received post-operative prophylactic antibiotic. Main antibiotics include cefazolin (41.3%, metronidazole (33.7%, ceftriaxone (31.7% and clindamycin (20.2%. Only 10 (21.9% patients received cefazolin or vancomycin for a total duration of 48 hours or less. Surgical wound infection occurred in 17 (16.3% patients during hospital stay. Adherence to antimicrobial prophylaxis guidelines was completely achieved in 14.4% of cases. Results of this study signified that adherence to existing guidelines was poor and the most common mistakes were over usage, inappropriate dosage and choosing of antibiotics.

Radioembolization: Is Prophylactic Embolization of Hepaticoenteric Arteries Necessary? A Systematic Review

Energy Technology Data Exchange (ETDEWEB)

Borggreve, Alicia S., E-mail: alicia.borggreve@gmail.com; Landman, Anadeijda J. E. M. C., E-mail: ajemclandman@gmail.com; Vissers, Coco M. J., E-mail: coco.vissers@hotmail.com; De Jong, Charlotte D., E-mail: charlotte-dejong@live.nl; Lam, Marnix G. E. H., E-mail: m.lam@umcutrecht.nl [University Medical Center Utrecht, Division of Radiology and Nuclear Medicine (Netherlands); Monninkhof, Evelyn M., E-mail: e.monninkhof@umcutrecht.nl [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care (Netherlands); Prince, Jip F., E-mail: jipfprince@gmail.com [University Medical Center Utrecht, Division of Radiology and Nuclear Medicine (Netherlands)

2016-05-15

PurposeTo study the effectiveness of prophylactic embolization of hepaticoenteric arteries to prevent gastrointestinal complications during radioembolization.MethodsA PubMed, Embase and Cochrane literature search was performed. We included studies assessing both a group of patients with and without embolization.ResultsOur search revealed 1401 articles of which title and abstract were screened. Finally, eight studies were included investigating 1237 patients. Of these patients, 456 received embolization of one or more arteries. No difference was seen in the incidence of gastrointestinal complications in patients with prophylactic embolization of the gastroduodenal artery (GDA), right gastric artery (RGA), cystic artery (CA) or hepatic falciform artery (HFA) compared to patients without embolization. Few complications were reported when microspheres were injected distal to the origin of these arteries or when reversed flow of the GDA was present. A high risk of confounding by indication was present because of the non-randomized nature of the included studies.ConclusionIt is advisable to restrict embolization to those hepaticoenteric arteries that originate distally or close to the injection site of microspheres. There is no conclusive evidence that embolization of hepaticoenteric arteries influences the risk of complications.

Radioembolization: Is Prophylactic Embolization of Hepaticoenteric Arteries Necessary? A Systematic Review

International Nuclear Information System (INIS)

Borggreve, Alicia S.; Landman, Anadeijda J. E. M. C.; Vissers, Coco M. J.; De Jong, Charlotte D.; Lam, Marnix G. E. H.; Monninkhof, Evelyn M.; Prince, Jip F.

2016-01-01

PurposeTo study the effectiveness of prophylactic embolization of hepaticoenteric arteries to prevent gastrointestinal complications during radioembolization.MethodsA PubMed, Embase and Cochrane literature search was performed. We included studies assessing both a group of patients with and without embolization.ResultsOur search revealed 1401 articles of which title and abstract were screened. Finally, eight studies were included investigating 1237 patients. Of these patients, 456 received embolization of one or more arteries. No difference was seen in the incidence of gastrointestinal complications in patients with prophylactic embolization of the gastroduodenal artery (GDA), right gastric artery (RGA), cystic artery (CA) or hepatic falciform artery (HFA) compared to patients without embolization. Few complications were reported when microspheres were injected distal to the origin of these arteries or when reversed flow of the GDA was present. A high risk of confounding by indication was present because of the non-randomized nature of the included studies.ConclusionIt is advisable to restrict embolization to those hepaticoenteric arteries that originate distally or close to the injection site of microspheres. There is no conclusive evidence that embolization of hepaticoenteric arteries influences the risk of complications.

Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease.

Science.gov (United States)

Gan-Or, Ziv; Dion, Patrick A; Rouleau, Guy A

2015-01-01

Parkinson disease (PD), once considered as a prototype of a sporadic disease, is now known to be considerably affected by various genetic factors, which interact with environmental factors and the normal process of aging, leading to PD. Large studies determined that the hereditary component of PD is at least 27%, and in some populations, single genetic factors are responsible for more than 33% of PD patients. Interestingly, many of these genetic factors, such as LRRK2, GBA, SMPD1, SNCA, PARK2, PINK1, PARK7, SCARB2, and others, are involved in the autophagy-lysosome pathway (ALP). Some of these genes encode lysosomal enzymes, whereas others correspond to proteins that are involved in transport to the lysosome, mitophagy, or other autophagic-related functions. Is it possible that all these factors converge into a single pathway that causes PD? In this review, we will discuss these genetic findings and the role of the ALP in the pathogenesis of PD and will try to answer this question. We will suggest a novel hypothesis for the pathogenic mechanism of PD that involves the lysosome and the different autophagy pathways.

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

Science.gov (United States)

Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G.

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins. PMID:29515558

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role.

Science.gov (United States)

Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4 + /CD25 + T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.

Directory of Open Access Journals (Sweden)

Philip O Scumpia

2017-07-01

Full Text Available Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs by pathogen recognition receptors (PRRs to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways contributing to the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, two PRR pathways-the Toll-like receptor (TLR and Stimulator of Interferon Gene (STING pathways-were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated a pro-inflammatory program while STING signaling activated an antiviral/type I interferon response with live but not killed S. aureus. This STING response was largely dependent on the cytosolic DNA sensor cyclic guanosine-adenosine synthase (cGAS. Using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus. TLR signaling was required for host defense, with its absence reducing interleukin (IL-1β production and neutrophil recruitment, resulting in increased bacterial growth. In contrast, absence of STING signaling had the opposite effect, enhancing the ability to restrict the infection. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered by S. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus.

Prophylactic Swallowing Exercises in Head and Neck Cancer Radiotherapy

DEFF Research Database (Denmark)

Mortensen, H R; Jensen, Kenneth; Aksglæde, K

2015-01-01

Many head and neck cancer (HNC) survivors experience reduced quality of life due to radiotherapy (RT)-related dysphagia. The aim of this prospective randomized trial was to evaluate the impact of prophylactic swallowing exercises on swallowing-related outcomes in HNC patients treated with curative...... of the dysphagia outcomes during and after treatment. Adherence to exercises was poor and dropouts due to especially fatigue were very frequent in both groups. Systematic swallowing exercises had no impact on swallowing outcomes within the first year after RT. Despite repeated supervised sessions, adherence...

Transcriptional repressor role of PocR on the 1,3-propanediol biosynthetic pathway by Lactobacillus panis PM1.

Science.gov (United States)

Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2014-06-01

The regulatory role of a transcriptional regulator (PocR) in the 1,3-propanediol biosynthetic pathway of Lactobacillus panis PM1 contributes to the optimization of 1,3-propanediol production by this strain, which potentially will lead to 1,3-propanediol manufacturing efficiencies. Lactobacillus panis PM1 can utilize a 1,3-propanediol (1,3-PDO) biosynthetic pathway, consisting of diol dehydratase (PduCDE) and 1,3-PDO dehydrogenase, as a NADH recycling system, to survive under various environmental conditions. In this study, we identified a key transcriptional repressor (PocR) which was annotated as a transcriptional factor of AraC family as part of the 1,3-PDO biosynthetic pathway of L. panis PM1. The over-expression of the PocR gene resulted in the significant repression (81 %) of pduC (PduCDE large subunit) transcription, and subsequently, the decreased activity of PduCDE by 22 %. As a result of the regulation of PduCDE, production of both 3-hydroxypropionaldehyde and 1,3-PDO in the PocR over-expressing strain were significantly decreased by 40 % relative to the control strain. These results clearly demonstrate the transcriptional repressor role of PocR in the 1,3-PDO biosynthetic pathway.

Radioprotective role of H2S/CSE pathway in Chang liver cells

International Nuclear Information System (INIS)

Pan Yan; Ye Shuang; Yuan Dexiao; Zhang Jianghong; Bai Yang; Shao Chunlin

2012-01-01

Radiation-induced liver cell damage may be life-threatening. Here, we investigated whether hydrogen sulfide (H 2 S)/cystathionine γ-lyase (CSE) pathway could serve the protective role toward radiation in normal human liver cells. Our data showed that pretreatment of cells with H 2 S donor, sodium hydrosulfide (NaHS) significantly attenuated radiation induced micronuclei formation and improved cell viability. However, the use of DL-propargylglycine (PPG), a potent inhibitor of CSE, markedly enhanced the cell-killing effect induced by radiation. Exposure of cells to 2 Gy γ-radiation led to significant increases of the endogenous H 2 S content. The mRNA and protein expressions of CSE also increased after radiation in a time-dependent manner, while the expression of cystathionine β-synthase (CBS), another endogenous H 2 S synthetase, did not change significantly. Notably, radiation induced production of reactive oxygen species (ROS) was significantly reversed by the pretreatment of NaHS, while blockage of CSE activity resulted in an enhanced ROS production in irradiated cells. Moreover, NaHS markedly suppressed radiation-induced phosphorylation of P53, decrease of Bcl-2/Bax, and activity of nuclear factor kappaB (NF-κB). In conclusion, our finding demonstrates that H 2 S/CSE pathway plays a radioprotection role by inhibiting radiation-induced ROS production, P53 phosphorylation, NF-κB activation and decrease of Bcl-2/Bax, indicating that modulation of H 2 S may be a novel protection strategy for liver radiation injury in radiotherapy.

The Salt Overly Sensitive (SOS) pathway: established and emerging roles.

Science.gov (United States)

Ji, Hongtao; Pardo, José M; Batelli, Giorgia; Van Oosten, Michael J; Bressan, Ray A; Li, Xia

2013-03-01

Soil salinity is a growing problem around the world with special relevance in farmlands. The ability to sense and respond to environmental stimuli is among the most fundamental processes that enable plants to survive. At the cellular level, the Salt Overly Sensitive (SOS) signaling pathway that comprises SOS3, SOS2, and SOS1 has been proposed to mediate cellular signaling under salt stress, to maintain ion homeostasis. Less well known is how cellularly heterogenous organs couple the salt signals to homeostasis maintenance of different types of cells and to appropriate growth of the entire organ and plant. Recent evidence strongly indicates that different regulatory mechanisms are adopted by roots and shoots in response to salt stress. Several reports have stated that, in roots, the SOS proteins may have novel roles in addition to their functions in sodium homeostasis. SOS3 plays a critical role in plastic development of lateral roots through modulation of auxin gradients and maxima in roots under mild salt conditions. The SOS proteins also play a role in the dynamics of cytoskeleton under stress. These results imply a high complexity of the regulatory networks involved in plant response to salinity. This review focuses on the emerging complexity of the SOS signaling and SOS protein functions, and highlights recent understanding on how the SOS proteins contribute to different responses to salt stress besides ion homeostasis.

Prophylactic first-line antibiotics reduce infectious fever and shorten hospital stay during chemotherapy-induced agranulocytosis in childhood acute myeloid leukemia.

Science.gov (United States)

Feng, Xiaoqin; Ruan, Yongsheng; He, Yuelin; Zhang, Yuming; Wu, Xuedong; Liu, Huayin; Liu, Xuan; He, Lan; Li, Chunfu

2014-01-01

There exists few pediatric data on the safety and efficacy of prophylactic antibiotics during chemotherapy-induced agranulocytosis. We prospectively studied the incidence of infection-related fever in 38 children, aged 2-16 years, with acute myeloid leukemia (AML) over 121 chemotherapy treatment cycles. A prophylactic group (n = 18) was given either vancomycin/cefepime (400 mg/m(2), q12 h/50 mg/kg, q12 h) or piperacillin/tazobactam (110 mg/kg, q12 h). Control patients (n = 20) received no preventive antibiotics. The prophylactic group (59 treatment cycles) experienced fever less frequently than the control group (0.4 vs. 0.9 events; p chemotherapy-induced agranulocytosis can effectively reduce the incidence of infectious fever and can shorten the average length of hospital stay, improving treatment success and quality of life. © 2014 S. Karger AG, Basel.

Indications and Outcomes of Prophylactic and Therapeutic Extracranial-to-intracranial Arterial Bypass for Cerebral Revascularization

Directory of Open Access Journals (Sweden)

Emre Gazyakan, MD, MSc

2015-04-01

Conclusions: The collaboration of neurosurgeons and plastic surgeons in performing EC-IC bypass can result in excellent outcomes with a high bypass patency rate and few complications, particularly for prophylactic EC-IC bypass.

General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review

DEFF Research Database (Denmark)

Hougaard, Anders; Tfelt-Hansen, Peer

2016-01-01

of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying...... reports of RCTs. RESULTS: A placebo arm was used in requiring more than 75,000 patient days, no difference...... was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine...

The psychological impact of breast reconstruction after prophylactic or therapeutic mastectomy for breast cancer

NARCIS (Netherlands)

Gopie, Jessica Premdee

2013-01-01

In this thesis the psychological impact of two types of breast reconstruction after prophylactic or therapeutic mastectomy for breast cancer was investigated with a prospective study including 202 patients from different hospitals in the South-West of the Netherlands between 2007-2012. With

Long-standing prophylactic therapy vs. episodic treatment in young people with severe haemophilia

DEFF Research Database (Denmark)

Ingerslev, J; Lethagen, Stefan Rune; Poulsen, Lone Hvitfeldt

2014-01-01

A was to challenge our hypothesis that on-demand treatment is inferior to prophylactic substitution in prevention of chronic joint disease at young age. The method involved an investigation of 40 patients from Russia (n = 27) and Denmark (n = 13) born between 1975 and 1990 with no history of inhibitors; Russian...

Predictors for contralateral prophylactic mastectomy in breast cancer patients

Science.gov (United States)

Fu, Yun; Zhuang, Zhigang; Dewing, Michelle; Apple, Sophia; Chang, Helena

2015-01-01

Background: In recent years, radical breast cancer surgery has been largely replaced by breast conservation treatment, due to early diagnosis and more effective adjuvant treatment. While breast conservation is mostly preferred, the trend of bilateral mastectomy has risen in the United States. The aim of this study is to determine factors influencing patients’ choice for having contralateral prophylactic mastectomy (CPM). Methods: This is a retrospective study of 373 patients diagnosed with primary invasive breast cancer who were treated by bilateral or unilateral mastectomy (BM or UM) at the Revlon/UCLA Breast Center between Jan. 2002 and Dec. 2010. In the BM group, only those with unilateral breast cancer who chose CPM were included in the analysis. Results: When compared with the UM group, the following factors were found to be associated with BM: younger age, pre-menopausal, a family history of breast/ovarian cancer, BRCA mutation, more breast biopsies, history of breast augmentation, having MRI study within 6 months before the surgery, more likely to have reconstruction and sentinel lymph node biopsy (SLNB) and fewer had neoadjuvant/adjuvant chemotherapy/radiation. When patients with bilateral breast cancer were excluded, multivariate logistic regression analysis indicated younger patients with negative nodes, SLNB as the only nodal surgery and positive family history were significant factors predicting CPM and immediate reconstruction using tissue expanders or implants. Conclusion: Younger age, lower TN stage, requiring only SLNB and high risk family history predict contralateral prophylactic mastectomy. Tissue expander/implant-based reconstructions were more frequently chosen by patients with BM. PMID:26097557

A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2.

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Cormier, J N; Hurst, R; Vasselli, J; Lee, D; Kim, C J; McKee, M; Venzon, D; White, D; Marincola, F M; Rosenberg, S A

1997-07-01

The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B. Despite differences in urine flow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). The overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2.

Plant-based solutions for veterinary immunotherapeutics and prophylactics.

Science.gov (United States)

Kolotilin, Igor; Topp, Ed; Cox, Eric; Devriendt, Bert; Conrad, Udo; Joensuu, Jussi; Stöger, Eva; Warzecha, Heribert; McAllister, Tim; Potter, Andrew; McLean, Michael D; Hall, J Christopher; Menassa, Rima

2014-12-31

An alarming increase in emergence of antibiotic resistance among pathogens worldwide has become a serious threat to our ability to treat infectious diseases according to the World Health Organization. Extensive use of antibiotics by livestock producers promotes the spread of new resistant strains, some of zoonotic concern, which increases food-borne illness in humans and causes significant economic burden on healthcare systems. Furthermore, consumer preferences for meat/poultry/fish produced without the use of antibiotics shape today's market demand. So, it is viewed as inevitable by the One Health Initiative that humans need to reduce the use of antibiotics and turn to alternative, improved means to control disease: vaccination and prophylactics. Besides the intense research focused on novel therapeutic molecules, both these strategies rely heavily on the availability of cost-effective, efficient and scalable production platforms which will allow large-volume manufacturing for vaccines, antibodies and other biopharmaceuticals. Within this context, plant-based platforms for production of recombinant therapeutic proteins offer significant advantages over conventional expression systems, including lack of animal pathogens, low production costs, fast turnaround and response times and rapid, nearly-unlimited scalability. Also, because dried leaves and seeds can be stored at room temperature for lengthy periods without loss of recombinant proteins, plant expression systems have the potential to offer lucrative benefits from the development of edible vaccines and prophylactics, as these would not require "cold chain" storage and transportation, and could be administered in mass volumes with minimal processing. Several biotechnology companies currently have developed and adopted plant-based platforms for commercial production of recombinant protein therapeutics. In this manuscript, we outline the challenges in the process of livestock immunization as well as the current

A risk prediction model for severe intraventricular hemorrhage in very low birth weight infants and the effect of prophylactic indomethacin.

Science.gov (United States)

Luque, M J; Tapia, J L; Villarroel, L; Marshall, G; Musante, G; Carlo, W; Kattan, J

2014-01-01

Develop a risk prediction model for severe intraventricular hemorrhage (IVH) in very low birth weight infants (VLBWI). Prospectively collected data of infants with birth weight 500 to 1249 g born between 2001 and 2010 in centers from the Neocosur Network were used. Forward stepwise logistic regression model was employed. The model was tested in the 2011 cohort and then applied to the population of VLBWI that received prophylactic indomethacin to analyze its effect in the risk of severe IVH. Data from 6538 VLBWI were analyzed. The area under ROC curve for the model was 0.79 and 0.76 when tested in the 2011 cohort. The prophylactic indomethacin group had lower incidence of severe IVH, especially in the highest-risk groups. A model for early severe IVH prediction was developed and tested in our population. Prophylactic indomethacin was associated with a lower risk-adjusted incidence of severe IVH.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

Science.gov (United States)

Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

2014-07-01

To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A peffect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

Prophylactic Breast Bud Radiotherapy for Patients Taking Bicalutamide: Should This Still Be Practised for Patients with Prostate Cancer?

Directory of Open Access Journals (Sweden)

R. Lewis

2012-01-01

Full Text Available Prophylactic breast bud radiotherapy is used to prevent gynaecomastia and mastalgia in patients with prostate cancer who are being treated with antiandrogen and oestrogen therapy. Here a case is presented of a patient who developed soft-tissue sarcoma of the breast subsequent to breast bud radiotherapy prior to bicalutamide hormone treatment. Bicalutamide is often prescribed for younger men in the adjuvant setting or as monotherapy for locally advanced disease. The data regarding the efficacy of prophylactic breast bud radiotherapy is reviewed, and it is proposed that alternative therapies should be considered such as tamoxifen.

Prophylactic ibuprofed administration during pelvic irradiation

International Nuclear Information System (INIS)

Stryker, J.A.; Demers, L.M.; Mortel, R.

1979-01-01

Thirty-five patients who were to begin pelvic irradiation for malignant disease were randomized to receive ibuprofen 400 mg P.O. q.i.d. during their radiotherapy or standard therapy for radiation-induced gastrointestinal symptoms. Seventeen of 19 patients in the ibuprofen group completed the protocol. There was no significant difference in the daily stool frequency between the ibuprofen and control patients during the 5 to 6 week course of pelvic irradiation; the incidence and severity of diarrhea was the same. There was no significant difference in the incidence of nausea reported by the patients but the severity of nausea was less in the ibuprofen group; none of the 17 patients in the ibuprofen group reported vomiting at any time, whereas, 27% of the patients in the control group reported vomiting. The difference was statistically significant (p < 0.05). The data suggest that prophylactic ibuprofen administration may be beneficial in reducing the severity of nausea and preventing radiation-induced vomiting in patients who receive pelvic irradiation

The causative role and therapeutic potential of the kynurenine pathway in neurodegenerative disease.

Science.gov (United States)

Amaral, Marta; Outeiro, Tiago F; Scrutton, Nigel S; Giorgini, Flaviano

2013-06-01

Metabolites of the kynurenine pathway (KP), which arise from the degradation of tryptophan, have been studied in detail for over a century and garnered the interest of the neuroscience community in the late 1970s and early 1980s with work uncovering the neuromodulatory potential of this pathway. Much research in the following decades has found that perturbations in the levels of KP metabolites likely contribute to the pathogenesis of several neurodegenerative diseases. More recently, it has become apparent that targeting KP enzymes, in particular kynurenine 3-monooxygenase (KMO), may hold substantial therapeutic potential for these disorders. Here we provide an overview of the KP, the neuroactive properties of KP metabolites and their role in neurodegeneration. We also discuss KMO as a therapeutic target for these disorders, and our recent resolution of the crystallographic structure of KMO, which will permit the development of new and improved KMO inhibitors which may ultimately expedite clinical application of these compounds.

The properties and Roles of Resonance-Stabilized Radicals in Photochemical Pathways in Titan's Atmosphere

Science.gov (United States)

Sebree, Joshua A.; Kidwell, Nathan; Zwier, Timothy

2010-11-01

In recent years, the Cassini satellite has been providing details about the composition of Titan's atmosphere. Recent data has shown the existence of polycyclic aromatic hydrocarbons (PAHs) at higher altitudes than previously expected including masses tentatively ascribed to naphthalene and anthracene. The formation of indene (C9H9) and naphthalene (C10H8), the simplest PAHs, and their derivatives are of great interest as similar mechanisms may lead to the formation of larger fused-ring systems. In recent years it has been proposed that resonance-stabilized radicals (RSRs) may play an important role as intermediates along these pathways. RSRs gain extra stability by delocalizing the unpaired electron through a neighboring conjugated π-system. Because of this extra stability, RSRs are able to build up in concentration, allowing for the creation of larger, more complex systems through their recombination with other RSRs. Mass-selective UV-visible spectra of two RSRs, phenylallyl and benzylallenyl radicals, have been recorded under jet-cooled conditions. These two radicals, while sharing the same radical conjugation, have unique properties. The roles these radicals may play in the formation of fused ring systems will be discussed along with recent photochemical results on reaction pathways starting from benzylallene through the benzylallenyl radical.

In vitro antiplasmodial activity and prophylactic potentials of extract and fractions of Trema orientalis (Linn.) stem bark.

Science.gov (United States)

Olanlokun, John Oludele; David, Oluwole Moses; Afolayan, Anthony Jide

2017-08-15

Trema orientalis (T. orientalis Linn) has been used in the management of malaria in the western part of Nigeria and despite its application in ethnomedicine, there is dearth of scientific evidence to justify the acclaimed prophylactic antimalarial usage of the plant. The aim of this study is to assess the in vitro antiplasmodial cell-free assay and chemopreventive efficacy of the methanol extract of the stem bark of T. orientalis and its fractions as a prophylactic regimen for malaria prevention. Also, the antimicrobial activities of the extract and the fractions were investigated. Vacuum liquid chromatography was used to obtain dichloromethane, ethylacetate and methanol fractions from the methanol extract of T. orientalis. The fractions were tested for their prophylactic and cell-free antimalarial activity using murine models and β-hematin formation assay respectively. Disc diffusion method was used to determine the antibacterial activity of the extract and its fractions against both Gram-positive and Gram-negative bacteria. In the prophylactic experiment, dichloromethane (DCMF), methanol fraction (MF) and extract (ME) (in this order) showed significant chemopreventive effects against P. berghei invasion of the red blood cells when compared with both Sulfadoxine-Pyrimethamine (SP) and untreated controls. Results of the in vitro study showed that the DCMF had the highest effect in preventing the formation of β-hematin when compared with other fractions. The DCMF also had the highest percentage inhibition of β-hematin formation when compared with chloroquine. The extract and fractions showed a concentration dependent antibacterial activity. Methanol extract had a pronounced inhibitory effect on Enterobacter cloaca ATCC 13047 and Enterococcus faecalis ATCC 29212. Serratia mercescens ATCC 9986 and Pseudomonas aeruginosa ATCC 19582 were the most susceptible bacteria. The results obtained showed that both extract and fractions of T. orientalis possessed

Long-term prophylactic insulin treatment can prevent spontaneous diabetes and thyroiditis development in the diabetes-prone bio-breeding rat, while short-term treatment is ineffective

NARCIS (Netherlands)

Visser, J.; Klatter, F; Vis, L; Groen, Harry; Strubbe, J.H.; Rozing, Nico

Objective: Prophylactic insulin treatment has been demonstrated to reduce diabetes development in the diabetes-prone bio-breeding (DP-BB) rat. These prophylactic insulin treatments were given from 50 to 150 days of age. However, several data indicate that the diabetogenic process in DP-BB rats

Cost-effectiveness analysis alongside a pilot study of prophylactic negative pressure wound therapy.

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Heard, Christopher; Chaboyer, Wendy; Anderson, Vinah; Gillespie, Brigid M; Whitty, Jennifer A

2017-02-01

Negative pressure wound therapy (NPWT) is increasingly used prophylactically following surgery despite limited evidence of clinical or cost-effectiveness. To evaluate whether NPWT is cost-effective compared to standard care, for the prevention of surgical site infection (SSI) in obese women undergoing elective caesarean section, and inform development of a larger trial. An economic evaluation was conducted alongside a pilot randomised controlled trial at one Australian hospital, in which women were randomised to NPWT (n = 44) or standard care (n = 43). A public health care provider perspective and time horizon to four weeks post-discharge was adopted. Cost-effectiveness assessment was based on incremental cost per SSI prevented and per quality-adjusted life year (QALY) gained. Patients receiving NPWT each received health care costing AU$5887 (±1038) and reported 0.069 (±0.010) QALYs compared to AU$5754 (±1484) and 0.066 (±0.010) QALYs for patients receiving standard care. NPWT may be slightly more costly and more effective than standard care, with estimated incremental cost-effectiveness ratios (ICERs) of AU$1347 (95%CI dominant- $41,873) per SSI prevented and AU$42,340 (95%CI dominant- $884,019) per QALY gained. However, there was considerable uncertainty around these estimates. NPWT may be cost-effective in the prophylactic treatment of surgical wounds following elective caesarean section in obese women. Larger trials could clarify the cost-effectiveness of NPWT as a prophylactic treatment for SSI. Sensitive capture of QALYs and cost offsets will be important given the high level of uncertainty around the point estimate cost-effectiveness ratio which was close to conventional thresholds. ACTRN12612000171819. Copyright © 2016 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy.

Science.gov (United States)

Yu, Jin-Tai; Tan, Lan

2012-04-01

Genetic variation in clusterin gene, also known as apolipoprotein J, has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, and plasma clusterin levels are associated with brain atrophy, baseline prevalence and severity, and rapid clinical progression in patients with AD, highlighting the importance of clusterin in AD pathogenesis. Emerging data suggest that clusterin contributes to AD through various pathways, including amyloid-β aggregation and clearance, lipid metabolism, neuroinflammation, and neuronal cell cycle control and apoptosis. Moreover, epigenetic regulation of the clusterin expression also seems to play an important role in the pathogenesis of AD. Emerging knowledge of the contribution of clusterin to the pathogenesis of AD presents new opportunities for AD therapy.

Do prophylactic antibiotics in gynecologic surgery prevent postoperative inflammatory complications? A systematic review.

Science.gov (United States)

Boesch, Cedric Emanuel; Pronk, Roderick Franziskus; Medved, Fabian; Hentschel, Pascal; Schaller, Hans-Eberhard; Umek, Wolfgang

2017-06-01

The aim of this study was to systematically review the literature on antibiotic prophylaxis in gynaecologic surgeries to prevent inflammatory complications after gynaecological operations. The study was carried out as a systematic review. Only randomised controlled trials of women undergoing gynaecological surgery were included. The Medline and the Cochrane library databases were searched from 1966 to 2016. The trials must have investigated an antibiotic intervention to prevent an inflammatory complication after gynaecological surgery. Trials were excluded if they were not randomised, uncontrolled or included obstetrical surgery. Prophylactic antibiotics prevent inflammatory complications after gynaecological surgery. Prophylactic antibiotics are more effective in surgery requiring access to the peritoneal cavity or the vagina. Cefotetan appears to be more capable in preventing the overall inflammatory complication rate than cefoxitin or cefazolin. No benefit has been shown for the combination of antibiotics as prophylaxis. No difference has been shown between the long-term and short-term use of antibiotics. There is no need for the primary use of an anaerobic antibacterial agent. Antibiotics help to prevent postoperative inflammatory complications after major gynecologic surgeries.

Prophylactic treatment to the fellow eye of patients with phakic lattice retinal detachment: analysis of failures and risks of treatment.

Science.gov (United States)

Folk, J C; Bennett, S R; Klugman, M R; Arrindell, E L; Boldt, H C

1990-01-01

The authors performed a retrospective analysis on 296 phakic patients who had bilateral lattice degeneration and a retinal detachment in one eye. The analysis was done to determine the complications of full prophylactic treatment to lattice and breaks in the fellow eye and to explain the reasons that this treatment sometimes did not prevent new retinal breaks or detachments. The patients were followed for a mean +/- SD of 7.415 +/- 5.422 years after their first detachment. Twenty-four new tears occurred in the fellow eyes during this time, seven (29.2%) of which were away from areas of visible lattice. Prophylactic treatment did not appear to cause new tears or increase the risk of detachment if a new tear occurred. It also did not compromise the surgical repair in those patients who had eyes in which new breaks or detachments developed. The risk of visual loss was similar in those patients receiving prophylactic treatment compared with those not receiving treatment.

Diuron treatment reveals the different roles of two cyclic electron transfer pathways in photosystem II in Arabidopsis thaliana.

Science.gov (United States)

Jin, Yujian; Chen, Si; Fan, Xiaoji; Song, Hao; Li, Xingxing; Xu, Jiahui; Qian, Haifeng

2017-04-01

Three ecotypes of Arabidopsis thaliana, ecotype Columbia (Wild type, Wt) and two mutants (pgr5 and ndf4), were used to evaluate the effects of diuron on photosynthetic activity of A. thaliana. It was found that diuron adversely affected the fresh weight and chlorophyll content of the plants. Chlorophyll fluorescence studies determined that the pgr5 mutant was more sensitive to diuron than Wt and the ndf4 mutant. Gene expression analysis revealed different roles for the two cyclic electron transfer (CET) pathways, NAD(P)H dehydrogenase (NDH) and proton gradient regulation (PGR5) pathways, in the plant after diuron treatment. For example, a gene in the NDH pathway, lhca5, was activated in the low dose (LD) group in the pgr5 mutant, but was down-regulated in the moderate dose (MD) group, along with two other NDH-related genes (ppl2 and ndhH). In the PGR5 pathway, the pgr5 gene was functional under conditions of increased stress (MD group), and was up-regulated to a greater extent in the ndf4 mutant than that in the Wt and pgr5 mutant. Our results suggest that the PGR5 pathway in plants is more important than the NDH pathway during resistance to environmental stress. Deficiencies in the PGR5 pathway could not be counteracted by the NDH pathway, but deficiencies in the NDH pathway could be overcome by stimulating PGR5. Copyright © 2016 Elsevier B.V. All rights reserved.

Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

Directory of Open Access Journals (Sweden)

Juan Rodríguez-Vita

Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

Effect of Prophylactic Ankle-Brace Use During a High School Competitive Basketball Season on Dynamic Postural Control.

Science.gov (United States)

Crockett, Nathan J; Sandrey, Michelle A

2015-08-01

Few studies have evaluated the long-term effects of prophylactic ankle-brace use during a sport season. To determine the effects of prophylactic ankle-brace use during a high school basketball season on dynamic postural control and functional tests. Prospective repeated-measures design. High school athletic facility. 21 healthy high school basketball athletes (13 girls, 8 boys). The order of testing was randomized using the Star Excursion Balance Test (SEBT) for posteromedial (PM), medial (M), and anteromedial (AM) directions and 3 functional tests (FT) consisting of the single-leg crossover hop, single-leg vertical jump, and the single-leg 6-m hop for time at pre-, mid-, and postseason. After pretesting, the ankle brace was worn on both limbs during the entire 16-wk competitive basketball season. SEBT for PM, M, and AM and 3 single-leg FTs. Dynamic postural control using the SEBT and the 3 FTs improved over time, notably from pretest to posttest. The left limb was different from the right limb during the single-leg vertical jump. Effect sizes were large for pretest to posttest for the 3 SEBT directions and 2 of the 3 FTs. The 16-wk basketball prophylactic ankle-brace intervention significantly improved dynamic postural control and single-limb FTs over time.

The role of the Fanconi anemia pathway in DNA repair and maintenance of genome stability

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Aleksandra M. Koczorowska

2014-05-01

Full Text Available The Fanconi anemia (FA pathway is one of the DNA repair systems involved in removal of DNA crosslinks. Proteins which belong to this pathway are crucial to the protection of genetic information, whereas disturbances in their function have serious implications for the whole organism. Biallelic mutations in FA genes are the cause of Fanconi anemia – a genetic disease which manifests itself through numerous congenital abnormalities, chromosomal instability and increased predisposition to cancer. The FA pathway is composed of fifteen proteins. Eight of them, in the presence of DNA interstrand crosslinks (ICLs, form a nuclear core complex responsible for monoubiquitination of FANCD2 and FANCI, which is a key step of ICL repair. FA proteins which are not involved in the monoubiquitination step participate in repair of DNA double strand breaks via homologous recombination. Some of the FA proteins, besides having a direct role in the repair of DNA damage, are engaged in replication, cell cycle control and mitosis. The unperturbed course of those processes determines the maintenance of genome stability.

Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

DEFF Research Database (Denmark)

Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

2010-01-01

To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).......To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

[DEONTOLOGICAL QUESTIONS IN PROPHYLACTIC OF ENDOSCOPIC COMPLICATIONS: THE SIGNIFICANCE OF RATIONAL AND PSYCHOLOGICAL FACTORS (analytical overview)].

Science.gov (United States)

Vernik, N V; Ivantsova, M A; Yashin, D I

2015-01-01

To evaluate the ways of reduction complications during endoscopic procedures based on principals of professional ethics and improving the quality of working area. Data of fundamental literature, evidence based medicine, science publications and internet portals. Deontology is the fundamental principle of medical practice and one of the main factors of professional effectiveness. Complications in endoscopy are often the investigations of deviation from the deontological principals. The whole number of psychological factors influences on professional activity of endoscopists, where the emotional "burn-out" syndrome (EBS) occupies one of the main places. Prophylactic and timely relief of EBS serves improvement of the practical work quality. Creation of favorable working area is the strategically important task in prophylactics of endoscopy complications. The questions of practical realization of deontological principles in endoscopy are the subject of further discussion.

Role of prophylactic ondansetron for prevention of spinal anaesthesia induced hypotension in lower segment caesarean section

International Nuclear Information System (INIS)

Abbas, N.

2016-01-01

Objective: To determine the efficacy of prophylactic administration of intravenous Ondansetron for prevention of spinal anaesthesia induced hypotension in lower segment caesarean section. Study Design: Double blinded randomized controlled trial. Place and Duration of Study: It was conducted in Anesthesiology department, CMH Rawalakot; from 3 Mar to 4 Jun 2014. Material and Methods: One hundred patients were selected for this study, and randomly divided in two groups of 50 each, using random numbers table. Both groups were preloaded with Ringer's lactate at dose of 10ml/kg. Group A received 04 mg of IV ondansetron 5 min prior to spinal anaesthesia, whereas Group B received normal saline 05 minutes before administration of Spinal Anaesthesia. Results: Average age of Group A was 28.62 +- 4.64 years, whereas that of Group B was 27.88 +- 3.98 (p-value= 0.394). Average weight of Group A was 70.30 +- 6.25 kg, whereas that of Group B was 70.74 +- 6.17 kg (p-value= 0.724). Hypotension was noted in 21 patients in group A (42 percent), whereas it was observed in 34 Patients in Group B (68 percent) (p-value= 0.009). Bradycardia was noted in 9 patients in Group A (18 percent) and 19 patients in Group B (p=0.026). Conclusion: Intravenous administration of 04 mg of intravenous ondansetron, 05 minutes prior to subarachnoid block, is effective in decreasing frequency of hypotension. (author)

The role of the stress-activated protein kinase (SAPK/JNK) signaling pathway in radiation-induced apoptosis

International Nuclear Information System (INIS)

Verheij, M.; Ruiter, G.A.; Zerp, S.F.; Bartelink, H.; Blitterswijk, W.J. van; Fuks, Z.; Haimovitz-Friedman, A.

1998-01-01

Ionizing radiation, like a variety of other cellular stress factors, initiates apoptosis, or programmed cell death, in many cell systems. This mode of radiation-induced cell kill should be distinguished from clonogenic cell death due to unrepaired DNA damage. Ionizing radiation not only exerts its effect on the nuclear DNA, but also at the plasma membrane level where it may activate multiple signal transduction pathways. One of these pathways is the stress-activated protein kinase (SAPK) cascade which transduces death signals from the cell membrane to the nucleus. This review discusses recent evidence on the critical role of this signaling system in radiation- and stress-induced apoptosis. An improved understanding of the mechanisms involved in radiation-induced apoptosis may ultimately provide novel strategies of intervention in specific signal transduction pathways to favorably alter the therapeutic ratio in the treatment of human malignancies. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Predicting adherence to prophylactic medication in adolescents with asthma: an application of the ASE-model

NARCIS (Netherlands)

van Es, S.M.; Kaptein, A.A.; Bezemer, P.D.; Nagelkerke, A.F.; Colland, V.T.; Bouter, L.M.

2002-01-01

An explanatory framework, referred to as the attitude/social influence/self-efficacy-model (ASE-model), was utilised to explain future self-reported adherence of adolescents to daily inhaled prophylactic asthma medication. The objective was to investigate the long-term influence of these earlier

Predicting adherence to prophylactic medication in adolescents with asthma : an application of the ASE-model

NARCIS (Netherlands)

van Es, Saskia M; Kaptein, Adrian A; Bezemer, P Dick; Nagelkerke, Ad F; Colland, Vivian T; Bouter, Lex M

An explanatory framework, referred to as the attitude/social influence/self-efficacy-model (ASE-model), was utilised to explain future self-reported adherence of adolescents to daily inhaled prophylactic asthma medication. The objective was to investigate the long-term influence of these earlier

Lack of benefit for prophylactic drugs of tension-type headache in adults : a systematic review

NARCIS (Netherlands)

Verhagen, Arianne P.; Damen, Leonie; Berger, Marjolein Y.; Passchier, Jan; Koes, Bart W.

Methods. We searched several databases from inception to August 2009. We selected randomized trials that reported the effects of prophylactic drugs in patients with TTH, with a pain measure (intensity, frequency, duration, improvement or index) as outcome measure. Two authors independently assessed

MicroRNA Roles in the NF-κB Signaling Pathway during Viral Infections

Directory of Open Access Journals (Sweden)

Zeqian Gao

2014-01-01

Full Text Available NF-κB signaling network is a crucial component of innate immunity. miRNAs are a subtype of small noncoding RNAs, involved in regulation of gene expression at the posttranscriptional level. Increasing evidence has emerged that miRNAs play an important role in regulation of NF-κB signaling pathway during viral infections. Both host and viral miRNAs are attributed to modulation of NF-κB activity, thus affecting viral infection and clearance. Understandings of the mechanisms of these miRNAs will open a direction for development of novel antivirus drugs.

Assessing the roles of impulsivity, food-related cognitions, BMI, and demographics in the dual pathway model of binge eating among men and women.

Science.gov (United States)

Mason, Tyler B; Lewis, Robin J

2015-08-01

The dual pathway model is a widely accepted model of binge eating that focuses on the role of sociocultural factors, negative affect, and dietary restraint. However, less is known about demographic (e.g., gender and ethnicity) differences in the model and the role of other variables in the model. To further our understanding of the dual pathway model of binge eating, the current study examined the role of demographics (i.e., gender, race, BMI, parental education and obesity), impulsivity, and food-related cognitions in the dual pathway model. A sample of college students completed a battery of measures. Multi-group structural equation modeling was used to evaluate the dual pathway model separately for men and women. Results supported the dual pathway model of binge eating among men and women, and also supported food-related cognitions as an important variable prior to binge eating. In other words, body shame was associated with more dietary restraint and negative affect, and in turn, dietary restraint and negative affect were associated with increased negative food-related cognitions. Then, food-related cognitions predicted binge eating. Additionally impulsivity was related to body shame, negative affect, and food-related cognitions, but was unrelated to binge eating after controlling for the other variables. Racial differences existed among women in BMI and body shame, but there were no racial differences among men. Our results suggest that the dual pathway model adequately explains binge eating among men and women, but that food-related cognitions may be an imporant anteceden to binge eating. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effective connectivity reveals important roles for both the hyperdirect (fronto-subthalamic) and indirect (fronto-striatal-pallidal) fronto-basal ganglia pathways during response inhibition

NARCIS (Netherlands)

Jahfari, S.; Waldorp, L.; van den Wildenberg, W.P.M.; Scholte, H.S.; Ridderinkhof, K.R.; Forstmann, B.U.

2011-01-01

Fronto-basal ganglia pathways play a crucial role in voluntary action control, including the ability to inhibit motor responses. Response inhibition might be mediated via a fast hyperdirect pathway connecting the right inferior frontal gyrus (rIFG) and the presupplementary motor area (preSMA) with

The EBI2 signalling pathway plays a role in cellular crosstalk between astrocytes and macrophages.

Science.gov (United States)

Rutkowska, Aleksandra; O'Sullivan, Sinead A; Christen, Isabelle; Zhang, Juan; Sailer, Andreas W; Dev, Kumlesh K

2016-05-11

EBI2 is a G protein-coupled receptor activated by oxysterol 7α, 25-dihydroxycholesterol (7α25HC) and regulates T cell-dependant antibody response and B cell migration. We recently found EBI2 is expressed in human astrocytes, regulates intracellular signalling and modulates astrocyte migration. Here, we report that LPS treatment of mouse astrocytes alters mRNA levels of EBI2 and oxysterols suggesting that the EBI2 signalling pathway is sensitive to LPS-mediated immune challenge. We also find that conditioned media obtained from LPS-stimulated mouse astrocytes induces macrophage migration, which is inhibited by the EBI2 antagonist NIBR189. These results demonstrate a role for the EBI2 signalling pathway in astrocytes as a sensor for immune challenge and for communication with innate immune cells such as macrophages.

[Cefamandole as prophylactic A.B. in abdominal surgery. Comparative study of cefamandole versus clindamycin/tobramycin (author's transl)].

Science.gov (United States)

Iarchy, J

1980-01-01

A prospective, randomized and controlled study of prophylactic A.B. was made in 100 patients prior to abdominal surgery. Fifty patients received 3 x 2 g of cefamandole I.V. within 24 hrs, the first dose being given at the time of anesthetic induction. Postoperative infections occurred in 2% of this group. Fifty patients received the association Clindamycin-Tobramycin (clindamycin 600 mg - tobramycin 80 mg/8 hrs) for 24 hrs, the first dose also at the induction of anesthesia. The complication rate in this group was 18%. The difference between those 2 groups is statistically significant (p less than 0.01). Cefamandole used as a prophylactic antibiotic in abdominal surgery reduces the incidence of postoperative wound infections when compared to the association clindamycin-tobramycin.

[HPV prophylactic vaccine coverage in France: Results of a survey among high school and university students in Marseilles' area].

Science.gov (United States)

Sabiani, L; Bremond, A; Mortier, I; Lecuyer, M; Boubli, L; Carcopino, X

2012-04-01

To assess HPV prophylactic vaccine coverage among French high school and university students as well as their level of education about this vaccine. An anonymous survey was conducted among 2500 high school and university students from the area of Marseilles, France, from December 2009 to April 2010. A total of 2018 questionnaires were collected (80.7% participation rate). Mean age of participants was 20 years (range, 15-45 years). Only 671 (35.4%) participants reported having been vaccinated against HPV, of whom 510 (73.4%) had completed the three injections scheme. Practice of cytological cervical cancer screening was not significantly influenced by vaccination status. Thus, 578 (45.2%) participants who had not been vaccinated already had had a cervical cytology performed, versus 295 (43.3%) vaccinated ones (P=0.445). Among those not being vaccinated, 671 (49.8%) fulfilled criteria for a catch-up vaccination, of whom only 325 (48.4%) agreed for such a catch-up. Main reasons given for refusal for a catch-up vaccination were the lack of information about HPV vaccine and fear of side effects. In total, 1722 (90%) considered themselves as educated about the HPV vaccine. Source of education was attributed to doctors and media by 54.4% and 53.7% of participants, respectively. Educational role attributed to school and university was poor (3.4%). Despite apparent satisfactory level of education, HPV prophylactic vaccine coverage among high school and university students appears to be insufficient. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Current Evidence regarding Prophylactic Antibiotics in Head and Neck and Maxillofacial Surgery

Science.gov (United States)

2014-01-01

Antibiotic prophylaxis is commonly used to decrease the rate of infections in head and neck surgery. The aim of this paper is to present the available evidence regarding the application of antibiotic prophylaxis in surgical procedures of the head and neck region in healthy patients. A systemic literature review based on Medline and Embase databases was performed. All reviews and meta-analyses based on RCTs in English from 2000 to 2013 were included. Eight out of 532 studies fulfilled all requirements. Within those, only seven different operative procedures were analyzed. Evidence exists for the beneficial use of prophylactic antibiotics for tympanostomy, orthognathic surgery, and operative tooth extractions. Unfortunately, little high-level evidence exists regarding the use of prophylactic antibiotics in head and neck surgery. In numerous cases, no clear benefit of antibiotic prophylaxis has been shown, particularly considering their potential adverse side effects. Antibiotics are often given unnecessarily and are administered too late and for too long. Furthermore, little research has been performed on the large number of routine cases in the above-mentioned areas of specialization within the last few years, although questions arising with respect to the treatment of high-risk patients or of specific infections are discussed on a broad base. PMID:25110703

Prophylactic Bracing Has No Effect on Lower Extremity Alignment or Functional Performance.

Science.gov (United States)

Hueber, Garrett A; Hall, Emily A; Sage, Brad W; Docherty, Carrie L

2017-07-01

Prophylactic ankle bracing is commonly used during physical activity. Understanding how bracing affects body mechanics is critically important when discussing both injury prevention and sport performance. The purpose is to determine if ankle bracing affects lower extremity mechanics during the Landing Error Scoring System test (LESS) and Sage Sway Index (SSI). Thirty physically active participants volunteered for this study. Participants completed the LESS and SSI in both a braced and unsupported conditions. Total errors were recorded for the LESS. Total errors and time (seconds) were recorded for the SSI. The Wilcoxon signed-rank test was utilized to evaluate any differences between the brace conditions for each dependent variable. A priori alpha level was set at pWilcoxon signed-rank test yielded no significant difference between the braced and unsupported conditions for the LESS (Z=-0.35, p=0.72), SSI time (Z=-0.36, p=0.72), or SSI Errors (Z=-0.37, p=0.71). Ankle braces had no effect on subjective clinical assessments of lower extremity alignment or postural stability. Utilization of a prophylactic support at the ankle did not substantially alter the proximal components of the lower kinetic chain. © Georg Thieme Verlag KG Stuttgart · New York.

Should prophylactic antibiotics be used routinely in epistaxis patients with nasal packs?

Science.gov (United States)

Nightingale, K; Patel, NN; Salib, RJ

2013-01-01

Introduction The current mainstream practice in otolaryngology departments relating to the use of prophylactic antibiotics in epistaxis patients requiring nasal packing is highly variable. This is due primarily to the lack of any validated guidelines. As such, we introduced a new treatment algorithm resulting in significant reduction of use in the systemic antibiotics, with emphasis instead on the use of topical antibiotics. The results were validated through a complete audit cycle. Methods A total of 57 patients undergoing nasal packing for spontaneous epistaxis were studied. Reaudit occurred after the implementation of new guidelines. Telephone surveys were conducted six weeks after hospital discharge, assessing infective nasal symptoms as well as rebleeding and readmission rates. Results Systemic antibiotic prescribing in anterior nasal packing fell by 58.2% between audit cycles with no statistically significant associated increase in infective nasal symptoms, rebleeding or readmission rates six weeks following hospital discharge. Conclusions Systemic prophylactic antibiotics are unnecessary in the majority of epistaxis patients with nasal packs. The use of topical antibiotics such as Naseptin® may be more appropriate, cheaper and as effective. Implementation of this treatment algorithm will help standardise systemic antibiotic usage in epistaxis patients with nasal packing and should reduce costs associated with unnecessary use of such medication. PMID:23317726

Balanites aegyptiaca ameliorates insulin secretion and decreases pancreatic apoptosis in diabetic rats: Role of SAPK/JNK pathway.

Science.gov (United States)

Hassanin, Kamel M A; Mahmoud, Mohamed O; Hassan, Hossam M; Abdel-Razik, Abdel-Razik H; Aziz, Lourin N; Rateb, Mostafa E

2018-06-01

SAPK-JNK pathway performs a significant role in the pathogenesis of type 2 diabetes. Balanites aegyptiaca (BA) is used as an anti-diabetic agent in folk medicine however its hypoglycemic mechanism is not fully elucidated. The current study aimed to evaluate the effect of crude extract, butanol, and dichloromethane fractions from BA on the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK-JNK) pathway in experimental diabetic rats. Six groups of male Wistar rats were included: normal control, diabetic, diabetic rats treated with crude, butanol or dichloromethane fraction from BA (50 mg/kg BW) and diabetic rats treated with gliclazide as a reference drug for one month. Our results suggested a protective role of treatment of diabetic rats with BA against oxidative stress-induced SAPK-JNK pathway. Moreover, BA treatment produced a reduction in plasma glucose, HbA 1c , lactic acid, lipid profile, malondialdehyde levels and produced an increase in insulin, reduced glutathione levels, catalase and superoxide dismutase activities compared with untreated diabetic rats. Moreover, it decreased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase 1, protein 53 and increased insulin receptor substrate 1 in rat pancreas while it increased glucose transporter 4 in rat muscle. Analysis of BA extracts by LC-HRMS revealed the presence of different saponins with reported hypoglycemic effect. In conclusion, BA exerted hypoglycemic, hypolipidemic, insulinotropic and antioxidant effects. Additionally, it reduced apoptosis in pancreatic β-cells and increased glucose uptake in muscle. These results suggest that the hypoglycemic effect of BA is due to the inhibition of the SAPK-JNK pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Mechanism of Notch Pathway Activation and Its Role in the Regulation of Olfactory Plasticity in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Simon Kidd

Full Text Available The neural plasticity of sensory systems is being increasingly recognized as playing a role in learning and memory. We have previously shown that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila melanogaster olfactory receptor neurons (ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. In this paper we address how long-term exposure to odor activates Notch and how Notch in conjunction with chronic odor mediates olfactory plasticity. We show that upon chronic odor exposure a non-canonical Notch pathway mediates an increase in the volume of glomeruli by a mechanism that is autonomous to ORNs. In addition to activating a pathway that is autonomous to ORNs, chronic odor exposure also activates the Notch ligand Delta in second order projection neurons (PNs, but this does not appear to require acetylcholine receptor activation in PNs. Delta on PNs then feeds back to activate canonical Notch signaling in ORNs, which restricts the extent of the odor induced increase in glomerular volume. Surprisingly, even though the pathway that mediates the increase in glomerular volume is autonomous to ORNs, nonproductive transsynaptic Delta/Notch interactions that do not activate the canonical pathway can block the increase in volume. In conjunction with chronic odor, the canonical Notch pathway also enhances cholinergic activation of PNs. We present evidence suggesting that this is due to increased acetylcholine release from ORNs. In regulating physiological plasticity, Notch functions solely by the canonical pathway, suggesting that there is no direct connection between morphological and physiological plasticity.

Decision making regarding prophylactic mastectomy: stability of preferences and the impact of anticipated feelings of regret.

Science.gov (United States)

van Dijk, Sandra; van Roosmalen, Mariëlle S; Otten, Wilma; Stalmeier, Peep F M

2008-05-10

Women who test positive for a BRCA1/2 mutation face difficult choices to manage their breast cancer risk; one of these choices is whether to opt for prophylactic mastectomy. Few data are available about this decision-making process. The current study provides data regarding the stability of risk-management preferences over time and the factors that are associated with these preferences. We analyzed data from 338 women who opted for breast cancer antigen (BRCA) testing. First, we prospectively assessed preferences of 80 BRCA mutation carriers at five different points in time ranging from 1 week after blood sampling up to 9 months after BRCA-test disclosure. Second, we applied univariate and multivariate regression analyses to examine which medical, sociodemographic, and psychological factors are related to a preference for prophylactic mastectomy. Ninety percent of the women already indicated a preference regarding risk management at baseline. Moreover, most women had stable preferences over time. Furthermore, anticipated feelings of regret in case of a hypothetical breast cancer diagnosis in the near future were strongly related to risk-management preference (odds ratio = 8.93; P preferences. Many of them may be sensitive to the possibility of regret in case of a bad outcome. We discuss whether possible regret in the future is a rational reason for opting for prophylactic mastectomy, or whether it signifies an emotional coping process or strategy in which the future costs are no longer fully considered.

Prophylactic interventions after delivery of placenta for reducing bleeding during the postnatal period.

Science.gov (United States)

Yaju, Yukari; Kataoka, Yaeko; Eto, Hiromi; Horiuchi, Shigeko; Mori, Rintaro

2013-11-26

There are several Cochrane systematic reviews looking at postpartum haemorrhage (PPH) prophylaxis in the third stage of labour and another Cochrane review investigating the timing of prophylactic uterotonics in the third stage of labour (i.e. before or after delivery of the placenta). There are, however, no Cochrane reviews looking at the use of interventions given purely after delivery of the placenta. Ergometrine or methylergometrine are used for the prevention of PPH in the postpartum period (the period after delivery of the infant) after delivery of the placenta in some countries. There are, furthermore, no Cochrane reviews that have so far considered herbal therapies or homeopathic remedies for the prevention of PPH after delivery of the placenta. To assess the effectiveness of available prophylactic interventions for PPH including prophylactic use of ergotamine, ergometrine, methylergometrine, herbal therapies, and homeopathic remedies, administered after delivery of the placenta, compared with no uterotonic agents as well as with different routes of administration for prevention of PPH after delivery of the placenta. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013), The Food and Drug Administration (FDA) (USA),  Medicines and Healthcare Products Regulatory Agency (MHRA) (UK), European Medicines Agency (EMA) (EU), Pharmaceuticals and Medical Devices Agency (PMDA) (Japan),  Therapeutic Goods Administration (TGA) (Australia), ClinicalTrials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform (ICTRP), University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; Japan), Japan Pharmaceutical Information Center Clinical Trials Information (Japic-CTI; Japan), Japan Medical Association Clinical Trial Registration (JMACCT CTR; Japan) (all on 30 April 2013) and reference lists of retrieved studies All randomised or quasi-randomised controlled trials comparing prophylactic

Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

Directory of Open Access Journals (Sweden)

Gabriela López-Armas

2016-01-01

Full Text Available Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1 control, (2 REMSD, (3 melatonin (10 mg/kg plus REMSD, (4 melatonin and intraperitoneal luzindole (once a day at 5 mg/kg plus REMSD, and (5 luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P<0.021. The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.

Aesthetic outcome, patient satisfaction, and health-related quality of life in women at high risk undergoing prophylactic mastectomy and immediate breast reconstruction.

Science.gov (United States)

Isern, A E; Tengrup, I; Loman, N; Olsson, H; Ringberg, A

2008-10-01

Prophylactic mastectomy is an effective risk-reducing option in women with hereditary increased risk of breast cancer. It may be combined with immediate reconstruction, with the intention of improving aesthetic outcome and health-related quality of life. Sixty-one women underwent prophylactic mastectomy and immediate breast reconstruction in Malmö, Sweden, between 1995 and 2003. Forty women underwent bilateral prophylactic mastectomy and immediate reconstruction. Ten of these had a previous breast cancer diagnosis. Twenty-one women underwent contralateral prophylactic mastectomy and immediate reconstruction after a previous breast cancer. Fifty-four of the women (89%) were evaluated clinically for aesthetic results and complications. Patient satisfaction and quality of life were evaluated with one study-specific and two standardised health-related questionnaires administered at time of clinical follow-up. Median follow-up time was 42 months (range 7-99 months). The position of the reconstructed breasts was judged as satisfactory in 77% of breasts. Symmetry in relation to the midline was adequate in 89% of breasts. A capsular contracture grade III according to Baker and indentation tonometry was observed in 1% of breasts (1/104). The complication rate was 18% (7% early and 11% late). Secondary corrections were carried out in 11% of breasts. The study-specific questionnaire revealed a high degree of satisfaction. No woman regretted the procedure, and all women would have chosen the same type of surgery again. An age-stratified comparison of Swedish women using the Short Form 36 Health Survey Questionnaire (SF-36) questionnaire was carried out for this study. The study population scores were high, suggesting that prophylactic mastectomy and immediate reconstruction on both physical and psychological issues in this retrospective study had no negative effect. Also, the Hospital Anxiety and Depression Scale (HAD) questionnaire did not suggest any increased anxiety or

Prophylactic transabdominal amnioinfusion in oligohydramnios for preterm premature rupture of membranes: increase of amniotic fluid index during latency period.

Science.gov (United States)

Garzetti, G G; Ciavattini, A; De Cristofaro, F; La Marca, N; Arduini, D

1997-01-01

This study was designed to: (i) evaluate the effect of amnioinfusion on the latency period in patients with oligohydramnios for preterm premature rupture of membranes, and (ii) to investigate the relationship between changes in the amniotic fluid index and fetal heart rate short-term variability by computerized Hewlett-Packard cardiotocography, longitudinally estimated before and after prophylactic amnioinfusion. All singleton pregnancies with prolonged premature rupture of membranes after 25 weeks of gestation and seen at the Institute of Obstetrics and Gynecology, University of Ancona (Italy), between January 1994 and June 1995 were included in the study. Transabdominal amnioinfusion with 150-350 ml warmed normal saline (25-50 ml/min) was performed at weekly intervals. Amniotic fluid volume was assessed ultrasonographically by means of the four-quadrant technique on a weekly basis before and after each amnioinfusion, as well as the short-term variability by a Hewlett-Packard computerized cardiotocographic system. 18 women were enrolled and underwent prophylactic transabdominal amnioinfusion at weekly intervals until delivery. Eighteen controls, who did not undergo prophylactic amnioinfusion, were recruited from our 1992-1993 series and included in the study. The median interval between premature rupture of membranes and delivery was 3.0 weeks (range 1-8 weeks), with an average delivery age of 33.0 weeks (range 27-36 weeks). The latency period was significantly longer in patients who underwent prophylactic amnioinfusion (mean +/- SD, 4.1 +/- 1.7 weeks) than in controls(1.7 +/- 1.0 weeks; p amnioinfusion. A direct relationship was observed between the amniotic fluid index and short-term variability (linear regression analysis r = 0.54, p = 0.04). The mean values of fetal movements recorded by computerized tomography during the 20 min of observation significantly increased after amnioinfusion in comparison with those before it (2.6 +/- 0.9 and 0.9 +/- 0

Value of prophylactic epilepsy surgery in contemporary neurosurgical practice

International Nuclear Information System (INIS)

Sugano, Hidenori; Arai, Hajime

2010-01-01

We have examined the value of prophylactic epilepsy surgery in diseases leading to intractable epilepsy. We reviewed 11 glioneuronal tumors (GNT) including gangliogliomas and dysembryoplastic neuroepithelial tumors, 11 cortical dysplasia (CD), and 33 cavernous angiomas (CA) diagnosed with MRI between the years 2000 and 2008 at the Department of Neurosurgery of Juntendo University in this study. We analyzed retrospectively the followings. Age of seizure onset and seizure severity. Region of each disease leading to intractable epilepsy. Seizure outcome after the surgery. Surgical morbidity. Ages of seizure onset of GNT, CD, and CA were 21.0±12.1, 1.3±7.5, 24.8±18.1 years, respectively. 81.8% of CD and GNT were intractable, however CA progresses to intractable epilepsy in 48.5%. The 66.7% of GNT with intractable seizures located in the mesial temporal lobe and 66.7% of CD had entra-temporal location. CA located in the mesial temporal lobe progressed to intractable epilepsy in 80%. Seizure free ratios of GNT, CD, and CA were 87.5%, 50.0%, 81.3%, respectively. In CDs where was impossible to carry out complete resection resulted in residual seizures. Neurological sequelae after surgery were observed in 3 cases. Morbidity ratios of motor weakness, speech difficulty, and memory disturbances are 4.6%, 4.6%, 2.3%, respectively. Majority of CD, GNT, and CA located in the mesial temporal lobe progress towards intractable epilepsy. Prophylactic epilepsy surgery by experienced surgeon with low complication rates can be an acceptable alternative for these pathological conditions. Seizure outcome of surgery for CD does not reach the success rates of those in GNT and CA. The cause of the unfavorable result in CD is the inapplicability to eloquent areas. Aggressive early surgery for CD may improve outcome considering neuronal plasticity of childhood. (author)

A novel murine model for evaluating bovine papillomavirus prophylactics/therapeutics for equine sarcoid-like tumours.

Science.gov (United States)

Bogaert, Lies; Woodham, Andrew W; Da Silva, Diane M; Martens, Ann; Meyer, Evelyne; Kast, W Martin

2015-09-01

Equine sarcoids are highly recurrent bovine papillomavirus (BPV)-induced fibroblastic neoplasms that are the most common skin tumours in horses. In order to facilitate the study of potential equine sarcoid prophylactics or therapeutics, which can be a slow and costly process in equines, a murine model for BPV-1 protein-expressing equine sarcoid-like tumours was developed in mice through stable transfection of BPV-1 E5 and E6 in a murine fibroblast tumour cell line (K-BALB). Like equine sarcoids, these murine tumour cells (BPV-KB) were of fibroblast origin, were tumorigenic and expressed BPV-1 proteins. As an initial investigation of the preclinical potential of this tumour model for equine sarcoids prophylactics, mice were immunized with BPV-1 E5E6 Venezuelan equine encephalitis virus replicon particles, prior to BPV-KB challenge, which resulted in an increased tumour-free period compared with controls, indicating that the BPV-KB murine model may be a valuable preclinical alternative to equine clinical trials.

Clinical and psychological impact of prophylactic implantable cardioverter-defibrillators in a community heart failure population.

LENUS (Irish Health Repository)

Arnous, S

2012-02-01

AIMS: ICD implantation for primary prevention of sudden cardiac death in patients with left ventricular systolic dysfunction (ejection fraction <\\/= 35%) has increased since the publication of the SCD-HEFT and MADIT-II data. The aim of this study is to examine the effectiveness and safety of prophylactic ICD use in a community heart failure population and to assess the impact on patient\\'s quality of life. METHODS AND RESULTS: Seventy-one ICDs were inserted between the years 2002 and 2006. The mean follow-up from time of insertion was 24 +\\/- 11 months. Eighteen patients (25%) had potentially life-saving therapy. Seven (10%) patients received inappropriate shocks. Complications were encountered in five patients (7%). CONCLUSION: In a community heart failure population, prophylactic ICD implantation is associated with a high incidence of life-saving therapy, a low complication rate and a high level of tolerability. These data indicate translation of clinical trial benefits to the general heart failure population.

The role of maternal perceptions and ethnic background in the mental health help-seeking pathway of adolescent girls

NARCIS (Netherlands)

I.J.E. Flink (Ilse); T.M.J. Beirens (Tinneke); D. Butte (Dick); H. Raat (Hein)

2013-01-01

textabstractMothers play a crucial role in the help-seeking pathway of adolescents. This study examined how mothers with different ethnic backgrounds perceive the issue of help-seeking for internalizing problems (e.g. depression) in adolescent girls. Seven focus group discussions were conducted with

Growth in children treated for acute lymphoblastic leukemia with and without prophylactic cranial irradiation

International Nuclear Information System (INIS)

Moell, C.; Garwicz, S.; Marky, L.; Melander, L.; Karlberg, J.

1988-01-01

Growth and weight gain were studied longitudinally over a period of four years in thirty-nine children treated for acute lymphoblastic leukemia. The children were divided into two groups according to treatment. Twenty-eight children were given prophylactic cranial irradiation and eleven children were treated without such irradiation. The duration of cytostatic treatment was three years in all cases. Average growth during the first two years was similar in the two groups, and the standard deviation scores (SDS) were below average. The rate of growth during the fourth year was significantly higher among those children who had not received cranial irradiation. After four years the average attained height had declined 0.5 SD for children treated with cranial irradiation and 0.2 SD for children without such treatment. Attained weight after four years had increased 0.4 SD more among those children who had not received irradiation. The results suggest that prophylactic cranial irradiation is responsible for the greater part of the prepubertal growth inhibition in these children. (authors)

Benefit of brain prophylactic irradiation in patients suffering from a small-cell bronchial cancer: retrospective study on 289 cases

International Nuclear Information System (INIS)

Assouline, A.; Tai, P.; Jancewicz, M.; Joseph, K.; Krzisch, C.; Yu, E.

2011-01-01

The authors report a study which aimed at determining the benefit of a brain prophylactic irradiation for patients suffering from a localized small-cell bronchial cancer and in partial response to the local-regional treatment of their disease. A retrospective analysis has been performed on a set of 289 patients who had been treated by chemo-radiotherapy with or without brain prophylactic irradiation between 1981 and 2007. Data are discussed in terms of remission level, survival with respect to the level of response to the local-regional treatment. Depending on this response level the irradiation increases or not the probability of global survival, or the probability of specific survival. Short communication

The prophylactic effect of neck irradiation combined with intra-oral electron beam irradiation for early tongue cancer

International Nuclear Information System (INIS)

Kawamori, Jiro; Kamata, Rikisaburo; Sanuki, Eiichi

1993-01-01

Between 1967 and 1988, 102 patients with Stage T1-2N0 squamous cell carcinoma of the tongue were treated with uneven fractional irradiation therapy (intra-oral electron beam irradiation with and without prophylactic ipsilateral upper neck irradiation at the Dept. of Radiology, Nihon University School of Medicine. Of 102 primary lesions, 89 cases were controlled with this therapy. In this study, these 89 cases were investigated in order to analyze the prophylactic effect of upper neck irradiation. Of the 89 patients, 42 received only intra-oral electron beam irradiation, while the remaining 47 received a combination of intra-oral electron beam irradiation and prophylactic irradiation to the ipsilateral upper neck. Twenty three of the 89 (25.8%) developed metastasis to the neck after the radiotherapy. A breakdown of these 23 cases reveals that 3/21 (14.3%) received 40-50 Gy to the neck, 9/26 (34.6%) received 20-40 Gy to the neck, and 11/42 (26.2%) received no irradiation to the neck (p<0.05 between first and second groups, and between first and third groups). The neck metastasis was classified into one of three categories based on the region in which it first appeared (ipsilateral upper neck, ipsilateral lower neck or contralateral neck). The first metastasis was seen in the ipsilateral upper neck, in the ipsilateral lower neck and in the contralateral neck in 17, 4 and 2 patients, respectively. In 1/19 who had received 40-50 Gy, in 5/21 who had received 20-40 Gy and in 11/42 who had not received neck irradiation the first metastasis appeared in the ipsilateral upper neck. The five year survival rate was 94%, 75% and 85% in the patients receiving 40-50 Gy, 20-40 Gy and no neck irradiation, respectively. These results suggest that prophylactic irradiation of 40-50 Gy to the ipsilateral upper neck might decrease the incidence of neck metastasis and slightly prolong survival time. (author)

Emerging Signaling Pathway in Arcuate Feeding-Related Neurons: Role of the Acbd7

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Damien Lanfray

2017-06-01

Full Text Available The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC and cocaine and amphetamine regulated transcript (CART and the neurons co-localizing agouti-related peptide (AgRP, neuropeptide Y (NPY, and gamma-aminobutyric acid (GABA. These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation. More recently, the metabolic involvement of further hypothalamic uncharacterized neuron populations has been suggested. In this review, we discuss the potential homeostatic implication of hypothalamic GABAergic neurons that produce Acyl-Coa-binding domain containing protein 7 (ACBD7, precursor of the nonadecaneuropeptide (NDN, which has recently been characterized as a potent anorexigenic neuropeptide capable of relaying the leptin anorectic/thermogenic effect via the melanocortin system.

Impact of Prophylactic Continuous Positive Airway Pressure on Transient Tachypnea of the Newborn and Neonatal Intensive Care Admission in Newborns Delivered by Elective Cesarean Section.

Science.gov (United States)

Celebi, Miray Yilmaz; Alan, Serdar; Kahvecioglu, Dilek; Cakir, Ufuk; Yildiz, Duran; Erdeve, Omer; Arsan, Saadet; Atasay, Begum

2016-01-01

This study aims to evaluate the effect of the prophylactic continuous positive airway pressure (CPAP) administration in the delivery room to newborns who were delivered by elective cesarean section (CS). Inborn infants with gestational age between 34(0/7) to 38(6/7) and born by elective CS were prospectively randomized to receive either prophylactic CPAP for 20 minutes via face mask or standardized care without CPAP in the delivery room. Primary outcomes were the incidence of transient tachypnea of the newborn (TTN) and neonatal intensive care unit (NICU) admission due to respiratory distress. A total of 259 infants with a mean gestational age of 37.7 ± 0.8 weeks and birth weight of 3,244 ± 477 g were included. A total of 134 infants received prophylactic CPAP and 125 received control standard care. The rate of NICU admission was significantly lower in prophylactic CPAP group (p = 0.045). Although the rate of TTN was lower in the prophylactic CPAP group, the difference was not statistically significant (p = 0.059). The rate of NICU admission due to respiratory distress was significantly higher in late-preterm cohort than early-term cohort (p CPAP administration decreases the rate of NICU admission without any side effect in late-preterm and early-term infants delivered by elective CS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.

Science.gov (United States)

Abraham, Karan J; Zhang, Xiao; Vidal, Ricardo; Paré, Geneviève C; Feilotter, Harriet E; Tron, Victor A

2016-04-01

Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Essential role of the NO signaling pathway in the hippocampal CA1 in morphine-associated memory depends on glutaminergic receptors.

Science.gov (United States)

Shen, Fang; Wang, Xue-Wei; Ge, Fei-Fei; Li, Yi-Jing; Cui, Cai-Lian

2016-03-01

The nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP-dependent protein kinase (PKG) signaling pathway has been reported to play a key role in memory processing. However, little is known about its role in drug-associated reward memory. Here, we report the following. 1) The NO pathway in the CA1 is critical for the retrieval of morphine-associated reward memory. Specifically, the nNOS, sGC and PKG protein levels in the CA1 were increased after the expression of morphine conditioned place preference (CPP). Intra-CA1 injection of an NOS, sGC or PKG inhibitor prevented morphine CPP expression. 2) The involvement of the NO pathway in morphine CPP requires NR2B-containing NMDA receptors (NR2B-NMDARs). NR2B-NMDAR expression was elevated in the CA1 following morphine CPP expression, and intra-CA1 injection of the NR2B-NMDAR antagonist Ro25-6981 not only blocked morphine CPP expression but also inhibited the up-regulation of nNOS, sGC and PKG. Moreover, the Ro25-6981-induced blockade of morphine CPP was abolished by intra-CA1 injection of a NOS substrate or an sGC activator. 3) The NR2B-NMDAR stimulated the NO pathway by up-regulating the phosphorylation of Akt(Ser473). Morphine CPP expression enhanced the pAkt(Ser473) level, which has been corroborated to regulate nNOS activity, and this effect was reversed by intra-CA1 injection of Ro25-6981. 4) GluR1 acted downstream of the NO pathway. The membrane level of GluR1 in the CA1 was increased after morphine CPP expression, and this effect was prevented by pre-injection of a PKG inhibitor into the CA1. Additionally, co-immunoprecipitation revealed an interaction between PKG and GluR1; this result further indicated a role of PKG in regulating GluR1 trafficking. Collectively, the results of our study demonstrated that the activation of the NR2B-NMDAR/NO/sGC/PKG signaling pathway is necessary for the retrieval of morphine-associated reward memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification

DEFF Research Database (Denmark)

Harboe, Morten; Garred, Peter; Karlstrøm, Ellen

2009-01-01

Complement activation plays an important role in human pathophysiology. The effect of classical pathway activation is largely dependent on alternative pathway (AP) amplification, whereas the role of AP for the down-stream effect of mannan-induced lectin pathway (LP) activation is poorly understood...... that AP amplification is quantitatively responsible for the final effect of initial specific LP activation. TCC generation on the solid phase was distinctly but less inhibited by anti-fD. C2 bypass of the LP pathway could be demonstrated, and AP amplification was also essential during C2 bypass in LP...... as shown by complete inhibition of TCC generation in C2-deficient serum by anti-fD and anti-properdin antibodies. In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway....

ROLE OF PI3K-AKT-mTOR AND Wnt SIGNALING PATHWAYS IN G1-S TRANSITION OF CELL CYCLE IN CANCER CELLS

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LAKSHMIPATHI eVADLAKONDA

2013-04-01

Full Text Available The PI3K–Akt pathway together with one of its downstream targets, the mechanistic target of rapamycin (mTOR is a highly deregulated pathway in cancers. There is a reciprocal relation between the Akt phosphorylation and mTOR complexes. Akt phosphorylated at T308 activates mTORC1 by inhibition of the tuberous sclerosis complex (TSC1/2, where as mTORC2 is recognized as the kinase that phosphorylates Akt at S473. Recent developments in the research on regulatory mechanisms of autophagy places mTORC1 mediated inhibition of autophagy at the central position in activation of proliferation and survival pathways in cells. Autophagy is a negative regulator of Wnt signaling pathway and the downstream effectors of Wnt signaling pathway, cyclin D1 and the c-Myc, are the key players in initiation of cell cycle and regulation of the G1-S transition in cancer cells. Production of reaction oxygen species (ROS, a common feature of a cancer cell metabolism, activates several downstream targets like the transcription factors FoxO, which play key roles in promoting the progression of cell cycle. A model is presented on the role of PI3K -Akt - mTOR and Wnt pathways in regulation of the progression of cell cycle through Go-G1-and S phases.

Alteration of intestinal microbiota in mice orally administered with salmon cartilage proteoglycan, a prophylactic agent.

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Krisana Asano

Full Text Available Proteoglycan (PG extracted from salmon nasal cartilage has potential to be a prophylactic agent. Daily oral administration of the PG attenuates systemic inflammatory response in the experimental mouse models. In this study, we applied the culture-independent approach to investigate an alteration of intestinal microbiota composition in PG-administered mice. The results indicated that the population level of bacilli increased in the small and large intestine upon PG administration. On the other hand, the population level of clostridia decreased in the large intestine. The proportion of bacteria that are able to ferment saccharides and produce short-chain fatty acids increased in the small intestine and decreased in the large intestine. Importantly, population level of probiotic lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the PG-administered mice. In addition, several disease-associated bacteria decreased upon PG administration. These results provided an understanding of the specific role of PG involved in host immune modulation and supported our hypothesis that daily oral administration of PG improves the overall balance in composition of the intestinal microbial community.

Prophylactic antibiotic regimen and dental implant failure: a meta-analysis.

Science.gov (United States)

Chrcanovic, B R; Albrektsson, T; Wennerberg, A

2014-12-01

The aim of this meta-analysis was to investigate whether there are any positive effects of prophylactic antibiotic regimen on implant failure rates and post-operative infection when performing dental implant treatment in healthy individuals. An electronic search without time or language restrictions was undertaken in March 2014. Eligibility criteria included clinical human studies, either randomised or not. The search strategy resulted in 14 publications. The I(2) statistic was used to express the percentage of the total variation across studies due to heterogeneity. The inverse variance method was used with a fixed- or random-effects model, depending on the heterogeneity. The estimates of relative effect were expressed in risk ratio (RR) with 95% confidence interval. Six studies were judged to be at high risk of bias, whereas one study was considered at moderate risk, and six studies were considered at low risk of bias. The test for overall effect showed that the difference between the procedures (use versus non-use of antibiotics) significantly affected the implant failure rates (P = 0.0002), with a RR of 0.55 (95% CI 0.41-0.75). The number needed to treat (NNT) to prevent one patient having an implant failure was 50 (95% CI 33-100). There were no apparent significant effects of prophylactic antibiotics on the occurrence of post-operative infections in healthy patients receiving implants (P = 0.520). A sensitivity analysis did not reveal difference when studies judged as having high risk of bias were not considered. The results have to be interpreted with caution due to the presence of several confounding factors in the included studies. © 2014 John Wiley & Sons Ltd.

Efficacy of Prophylactic Antibiotics at Peritoneal Catheter Insertion on Early Peritonitis: Data from the Catheter Section of the French Language Peritoneal Dialysis Registry.

Science.gov (United States)

Lanot, Antoine; Lobbedez, Thierry; Bechade, Clémence; Verger, Christian; Fabre, Emmanuel; Dratwa, Max; Vernier, Isabelle

2016-01-01

International guidelines recommend the use of a prophylactic antibiotic before the peritoneal dialysis (PD) catheter can be inserted. The main objective of this study was to assess whether this practice is associated with a lower risk of early peritonitis and to estimate the magnitude of the centre effect. A retrospective, multi-centric study was conducted, in which data from the French Language Peritoneal Dialysis Registry was analysed. Patients were separated into 2 groups based on whether or not prophylactic antibiotics were used prior to catheter placement. Out of the 2,014 patients who had a PD catheter placed between February 1, 2012 and December 31, 2014, 1,105 were given a prophylactic antibiotic. In a classical logit model, the use of prophylactic antibiotics was found to protect the individual against the risk of early peritonitis (OR 0.67, 95% CI 0.49-0.92). However, this association lost significance in a mixed logistic regression model with centre as a random effect: OR 0.73 (95% CI 0.48-1.09). Covariates associated with the risk of developing early peritonitis were age over 65: OR 0.73 (95% CI 0.39-0.85), body mass index over 35 kg/m2: OR 1.99 (95% CI 1.13-3.47), transfer to PD due to graft failure: OR 2.24 (95% CI 1.22-4.11), assisted PD: OR 1.96 (95% CI 1.31-2.93), and the use of the Moncrief technique: OR 3.07 (95% CI 1.85-5.11). There is a beneficial effect of prophylactic antibiotic used prior to peritoneal catheter placement, on the occurence of early peritonitis. However, the beneficial effect could be masked by a centre effect. © 2016 S. Karger AG, Basel.

Educators' expectations of roles, employability and career pathways of registered and enrolled nurses in Australia.

Science.gov (United States)

Jacob, Elisabeth R; McKenna, Lisa; D'Amore, Angelo

2016-01-01

In Australia, like other countries, two levels of nurse are registered for entry to practice. Educational changes for second level nurses in Australia have led to questions regarding roles and career options. This paper reports on interviews with nursing course coordinators to examine educator expectations of roles and career pathways of registered and enrolled nurses. Coordinators of eight degree (registered) and diploma (enrolled) nursing programs were interviewed to determine their opinions on roles and careers that students were prepared for. Transcripts were thematically analysed. Educators reported similar graduate roles, although high acuity care was primarily the role of registered nurses. Career expectations differed with enrolled nurses having limited advancement opportunity, and registered nurses greater career options. Health organisations were unprepared to accommodate increased practice scope of enrolled nurses and limited work practice through policies stipulating who could perform procedures. Organisational health policies need to accommodate increased enrolled nurse skill base. Education of practising nurses is necessary regarding increased scope of enrolled nurse practice to ensure they are used to their full potential. Increasing patient acuity requires more registered nurses, as enrolled nurses are unprepared to care for complex or deteriorating patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness and Value of Prophylactic 5-Layer Foam Sacral Dressings to Prevent Hospital-Acquired Pressure Injuries in Acute Care Hospitals: An Observational Cohort Study.

Science.gov (United States)

Padula, William V

The purpose of this study was to examine the effectiveness and value of prophylactic 5-layer foam sacral dressings to prevent hospital-acquired pressure injury rates in acute care settings. Retrospective observational cohort. We reviewed records of adult patients 18 years or older who were hospitalized at least 5 days across 38 acute care hospitals of the University Health System Consortium (UHC) and had a pressure injury as identified by Patient Safety Indicator #3 (PSI-03). All facilities are located in the United States. We collected longitudinal data pertaining to prophylactic 5-layer foam sacral dressings purchased by hospital-quarter for 38 academic medical centers between 2010 and 2015. Longitudinal data on acute care, hospital-level patient outcomes (eg, admissions and PSI-03 and pressure injury rate) were queried through the UHC clinical database/resource manager from the Johns Hopkins Medicine portal. Data on volumes of dressings purchased per UHC hospital were merged with UHC data. Mixed-effects negative binomial regression was used to test the longitudinal association of prophylactic foam sacral dressings on pressure injury rates, adjusted for hospital case-mix and Medicare payments rules. Significant pressure injury rate reductions in US acute care hospitals between 2010 and 2015 were associated with the adoption of prophylactic 5-layer foam sacral dressings within a prevention protocol (-1.0 cases/quarter; P = .002) and changes to Medicare payment rules in 2014 (-1.13 cases/quarter; P = .035). Prophylactic 5-layer foam sacral dressings are an effective component of a pressure injury prevention protocol. Hospitals adopting these technologies should expect good value for use of these products.

A pivotal role of the jasmonic acid signal pathway in mediating radiation-induced bystander effects in Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Wang, Ting; Xu, Wei; Deng, Chenguang; Xu, Shaoxin; Li, Fanghua; Wu, Yuejin; Wu, Lijun [Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Key Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province, Hefei 230031 (China); Bian, Po, E-mail: bianpo@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Key Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province, Hefei 230031 (China)

2016-09-15

Highlights: • The JA signal pathway plays a pivotal role in mediating radiation-induced bystander effects in Arabidopsis thaliana. • The JA signal pathway is involved in both the generation of bystander signals in irradiated roots and radiation responses in bystander aerial plants. • Over-accumulation of endogenous JA enhances the radiosensitivity of plants in terms of RIBE. - Abstract: Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have been well demonstrated in vivo, little is known about their underlying mechanisms, particularly with regard to the participating signaling molecules and signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive derivatives are well accepted as systemic signal transducers that are produced in response to various environmental stresses. It is therefore speculated that the JA signal pathway might play a potential role in mediating radiation-induced bystander signaling of root-to-shoot. In the present study, pretreatment of seedlings with Salicylhydroxamic acid, an inhibitor of lipoxigenase (LOX) in JA biosynthesis, significantly suppressed RIBE-mediated expression of the AtRAD54 gene. After root irradiation, the aerial parts of A. thaliana mutants deficient in JA biosynthesis (aos) and signaling cascades (jar1-1) showed suppressed induction of the AtRAD54 and AtRAD51 genes and TSI and 180-bp repeats, which have been extensively used as endpoints of bystander genetic and epigenetic effects in plants. These results suggest an involvement of the JA signal pathway in the RIBE of plants. Using the root micro-grafting technique, the JA signal pathway was shown to participate in both the generation of bystander signals in irradiated root cells and radiation responses in the bystander aerial parts of plants. The over-accumulation of endogenous JA in mutant fatty acid oxygenation up-regulated 2 (fou2), in which mutation of the Two Pore Channel 1 (TPC1) gene up-regulates expression of the LOX

Initiation of CPAP therapy for OSA: does prophylactic humidification during CPAP pressure titration improve initial patient acceptance and comfort?

Science.gov (United States)

Wiest, G H; Harsch, I A; Fuchs, F S; Kitzbichler, S; Bogner, K; Brueckl, W M; Hahn, E G; Ficker, J H

2002-01-01

Heated humidifiers (HH) enable effective treatment of upper airway dryness during nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnoea (OSA), but the role of prophylactic use of HH during the initiation of nCPAP treatment has not been studied so far. The aim of the present study was to investigate whether prophylactic HH during the initiation of CPAP would result in improved initial patient comfort and acceptance. In 44 consecutive, previously untreated OSA patients with no history of upper airway dryness, CPAP titration with and without HH was performed on two consecutive nights in a randomised order. The patients were interviewed after each treatment night in order to establish the comfort of the treatment, and, after the second treatment, they were asked which of the two nights they considered more pleasant, and which treatment they would prefer for long-term use. Following CPAP titration with HH, 32 patients (73%) claimed to have had a better night's sleep than usual (i.e. without CPAP treatment) compared with 33 patients (75%) saying the same following CPAP treatment without HH. For 21 patients (47.7%) treatment with HH was more pleasant, 23 (52.3%) saw no difference or said that treatment without HH was more pleasant. Nineteen patients (43.2%) gave preference to treatment with HH for long-term use, while 25 patients (56.8%) had no preference or said they would prefer treatment without HH. The use of HH during the initiation phase of CPAP treatment was associated neither with an initial improvement in comfort nor with greater initial treatment acceptance. Copyright 2002 S. Karger AG, Basel

Prophylactic Antibiotics for Elective Laparoscopic Cholecystectomy.

Science.gov (United States)

Smith, J Patrick; Samra, Navdeep S; Ballard, David H; Moss, Jonathan B; Griffen, Forrest D

2018-04-01

Surgical site infections with elective laparoscopic cholecystectomy are less frequent and less severe, leading some to suggest that prophylactic antibiotics (PA) are no longer indicated. We compared the incidence of surgical site infections before and after an institutional practice change of withholding PA for elective laparoscopic cholecystectomy. Between May 7, 2013, and March 11, 2015, no PA were given to patients selected for elective cholecystectomy by two surgeons at a single center. The only patients excluded were those who received antibiotics before surgery for any reason. All others, including those at high risk for infection, were included. The incidence and severity of infections were compared with historical controls treated with prophylaxis by the same two surgeons from November 6, 2011, to January 13, 2013. There were 268 patients in the study group and 119 patients in the control group. Infection occurred in 3.0 per cent in the study group compared with 0.9 per cent in the controls (P = 0.29). All infections were mild except one. Based on these data, the routine use of PA for elective laparoscopic cholecystectomy is not supported.

The prophylactic reduction of aluminium intake.

Science.gov (United States)

Lione, A

1983-02-01

The use of modern analytical methods has demonstrated that aluminium salts can be absorbed from the gut and concentrated in various human tissues, including bone, the parathyroids and brain. The neurotoxicity of aluminium has been extensively characterized in rabbits and cats, and high concentrations of aluminium have been detected in the brain tissue of patients with Alzheimer's disease. Various reports have suggested that high aluminium intakes may be harmful to some patients with bone disease or renal impairment. Fatal aluminium-induced neuropathies have been reported in patients on renal dialysis. Since there are no demonstrable consequences of aluminium deprivation, the prophylactic reduction of aluminium intake by many patients would appear prudent. In this report, the major sources of aluminium in foods and non-prescription drugs are summarized and alternative products are described. The most common foods that contain substantial amounts of aluminium-containing additives include some processed cheeses, baking powders, cake mixes, frozen doughs, pancake mixes, self-raising flours and pickled vegetables. The aluminium-containing non-prescription drugs include some antacids, buffered aspirins, antidiarrhoeal products, douches and haemorrhoidal medications. The advisability of recommending a low aluminium diet for geriatric patients is discussed in detail.

Prophylactic Efficacy of Quercetin 3-β-O-d-Glucoside against Ebola Virus Infection.

Science.gov (United States)

Qiu, Xiangguo; Kroeker, Andrea; He, Shihua; Kozak, Robert; Audet, Jonathan; Mbikay, Majambu; Chrétien, Michel

2016-09-01

Ebola outbreaks occur on a frequent basis, with the 2014-2015 outbreak in West Africa being the largest one ever recorded. This outbreak has resulted in over 11,000 deaths in four African countries and has received international attention and intervention. Although there are currently no approved therapies or vaccines, many promising candidates are undergoing clinical trials, and several have had success in promoting recovery from Ebola. However, these prophylactics and therapeutics have been designed and tested only against the same species of Ebola virus as the one causing the current outbreak. Future outbreaks involving other species would require reformulation and possibly redevelopment. Therefore, a broad-spectrum alternative is highly desirable. We have found that a flavonoid derivative called quercetin 3-β-O-d-glucoside (Q3G) has the ability to protect mice from Ebola even when given as little as 30 min prior to infection. Furthermore, we have demonstrated that this compound targets the early steps of viral entry. Most promisingly, antiviral activity against two distinct species of Ebola virus was seen. This study serves as a proof of principle that Q3G has potential as a prophylactic against Ebola virus infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications.

Science.gov (United States)

Kou, Jinghong; Yang, Junling; Lim, Jeong-Eun; Pattanayak, Abhinandan; Song, Min; Planque, Stephanie; Paul, Sudhir; Fukuchi, Ken-Ichiro

2015-02-01

Accumulation of amyloid beta-peptide (Aβ) in the brain is hypothesized to be a causal event leading to dementia in Alzheimer's disease (AD). Aβ vaccination removes Aβ deposits from the brain. Aβ immunotherapy, however, may cause T cell- and/or Fc-receptor-mediated brain inflammation and relocate parenchymal Aβ deposits to blood vessels leading to cerebral hemorrhages. Because catalytic antibodies do not form stable immune complexes and Aβ fragments produced by catalytic antibodies are less likely to form aggregates, Aβ-specific catalytic antibodies may have safer therapeutic profiles than reversibly-binding anti-Aβ antibodies. Additionally, catalytic antibodies may remove Aβ more efficiently than binding antibodies because a single catalytic antibody can hydrolyze thousands of Aβ molecules. We previously isolated Aβ-specific catalytic antibody, IgVL5D3, with strong Aβ-hydrolyzing activity. Here, we evaluated the prophylactic and therapeutic efficacy of brain-targeted IgVL5D3 gene delivery via recombinant adeno-associated virus serotype 9 (rAAV9) in an AD mouse model. One single injection of rAAV9-IgVL5D3 into the right ventricle of AD model mice yielded widespread, high expression of IgVL5D3 in the unilateral hemisphere. IgVL5D3 expression was readily detectable in the contralateral hemisphere but to a much lesser extent. IgVL5D3 expression was also confirmed in the cerebrospinal fluid. Prophylactic and therapeutic injection of rAAV9-IgVL5D3 reduced Aβ load in the ipsilateral hippocampus of AD model mice. No evidence of hemorrhages, increased vascular amyloid deposits, increased proinflammatory cytokines, or infiltrating T-cells in the brains was found in the experimental animals. AAV9-mediated anti-Aβ catalytic antibody brain delivery can be prophylactic and therapeutic options for AD.

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

Science.gov (United States)

Crighton, Gemma L; Estcourt, Lise J; Wood, Erica M; Trivella, Marialena; Doree, Carolyn; Stanworth, Simon

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004 and updated in 2012 that addressed four separate questions: therapeutic-only versus prophylactic platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. We have now split this review into four smaller reviews looking at these questions individually; this review is the first part of the original review. Objectives To determine whether a therapeutic-only platelet transfusion policy (platelet transfusions given when patient bleeds) is as effective and safe as a prophylactic platelet transfusion policy (platelet transfusions given to prevent bleeding, usually when the platelet count falls below a given trigger level) in patients with haematological disorders undergoing myelosuppressive chemotherapy or stem cell transplantation. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 July 2015. Selection criteria RCTs involving transfusions of platelet concentrates prepared either from individual units of whole blood or by apheresis, and given to prevent or treat bleeding in patients with malignant haematological disorders receiving myelosuppressive chemotherapy or undergoing HSCT. Data collection and analysis We used standard methodological procedures

The use of prophylactic partial exchange tranfusion in pregnancies associated with sickle cell hemoglobinopathies.

Science.gov (United States)

Morrison, J C; Wiser, W L

1976-11-01

Sickle cell anemia is associated with an alarming attrition rate during pregnancy. The maternal morbidity rate, perinatal wastage rate, and the incidence of severe morbidity in both mother and child are elevated above acceptable limits. In most cases, these statistics have been compiled using conservative therapeutic modalities. In contrast, this report utilizes prophylactic partial exchange transfusion therapy in patients with severe sickle cell hemoglobinopathies. The protocol involves the introduction of 750-1000 cc of buffy coat, poor washed red cells exchanged with 1000-1500 cc whole blood during phlebotomy at 28 weeks' gestation and again prior to term. Thirty-six consecutive pregnant patients with sickle cell anemia have been managed in this fashion. The one maternal mortality occurred in a patient who did not complete the protocol. Major maternal morbidity and perinatal wastage rates were significantly decreased. Two cases of serum hepatitis occurred. It appears from these data that the use of prophylactic partial exchange transfusion in pregnant patients with severe sickle cell hemoglobinopathies can be of benefit. Further trials of this method seem justified by these results to assess completely the benefit-risk ratio of this procedure.

Efficacy and Safety of Prophylactic Uterine Artery Embolization in Pregnancy Termination with Placenta Previa

Energy Technology Data Exchange (ETDEWEB)

Pei, Renguang, E-mail: mediprg@bjmu.edu.cn; Wang, Guoxiang; Wang, Heping; Huang, Xinyu; Yan, Xiaoxing; Yang, Xiaohua [Yijishan Hospital of Wannan Medical College, Department of Interventional Therapy (China)

2017-03-15

PurposeTo appraise the efficacy and safety of prophylactic uterine artery embolization in pregnancy termination with placenta previa.MethodsA cohort of 54 consecutive patients with placenta previa underwent prophylactic uterine artery embolization before vaginal delivery from February 2012 to March 2015. Vaginal delivery was attempted in all patients. Cesarean section or hysterectomy was introduced when vaginal delivery failed.ResultsVaginal delivery succeeded in 50 patients (93.6%) and failed in 4 patients (6.4%), thereupon converted to cesarean delivery. No patients resorted to hysterectomy. Six patients (11.1%) underwent blood transfusion. None of clinical characteristics, including maternal age, gestational age, history of abortion, history of cesarean delivery, and volume of vaginal bleeding, was significantly associated with complete placenta previa (P > 0.05). However, patients with complete placenta previa had a significantly lower successful rate of vaginal delivery than did patients without complete placenta previa (81 vs 100%, P = 0.038). The rate of complications was 3.7%. No major complications were observed.ConclusionUterine artery embolization is an effective and safe technique to assist pregnancy termination with placenta previa, which may lower the risk of cesarean section, hysterectomy, and blood transfusion.

Efficacy and Safety of Prophylactic Uterine Artery Embolization in Pregnancy Termination with Placenta Previa

International Nuclear Information System (INIS)

Pei, Renguang; Wang, Guoxiang; Wang, Heping; Huang, Xinyu; Yan, Xiaoxing; Yang, Xiaohua

2017-01-01

PurposeTo appraise the efficacy and safety of prophylactic uterine artery embolization in pregnancy termination with placenta previa.MethodsA cohort of 54 consecutive patients with placenta previa underwent prophylactic uterine artery embolization before vaginal delivery from February 2012 to March 2015. Vaginal delivery was attempted in all patients. Cesarean section or hysterectomy was introduced when vaginal delivery failed.ResultsVaginal delivery succeeded in 50 patients (93.6%) and failed in 4 patients (6.4%), thereupon converted to cesarean delivery. No patients resorted to hysterectomy. Six patients (11.1%) underwent blood transfusion. None of clinical characteristics, including maternal age, gestational age, history of abortion, history of cesarean delivery, and volume of vaginal bleeding, was significantly associated with complete placenta previa (P > 0.05). However, patients with complete placenta previa had a significantly lower successful rate of vaginal delivery than did patients without complete placenta previa (81 vs 100%, P = 0.038). The rate of complications was 3.7%. No major complications were observed.ConclusionUterine artery embolization is an effective and safe technique to assist pregnancy termination with placenta previa, which may lower the risk of cesarean section, hysterectomy, and blood transfusion.

Prophylactic clipping for the prevention of bleeding following wide-field endoscopic mucosal resection of laterally spreading colorectal lesions: an economic modeling study.

Science.gov (United States)

Bahin, Farzan F; Rasouli, Khalid N; Williams, Stephen J; Lee, Eric Y T; Bourke, Michael J

2016-08-01

Clinically significant bleeding (CSPEB) is the most common adverse event following endoscopic mucosal resection (EMR) of large sessile and laterally spreading colorectal lesions (LSLs), and is associated with morbidity and resource utilization. CSPEB occurs more frequently with proximal LSLs. Prophylactic clipping of the post-EMR defect may be beneficial in CSPEB prevention. The aim of this study was to determine the cost-effectiveness of a prophylactic clipping strategy. We hypothesized that prophylactic clipping in the proximal colon was cost-effective. An economic model was applied to outcomes from the Australian Colonic Endoscopic Mucosal Resection (ACE) Study. Clip distances of 3, 5, 8, and 10 mm were analyzed. The cost of treating CSPEB was determined from an independent costing agency. The funds needed to spend (FNS) was the cost incurred in order to prevent one episode of CSPEB. A break-even analysis was performed to determine cost equivalence of the costs of clipping and CSPEB. Outcomes of 1717 LSLs (mean size 35.8 mm; 52.6 % proximal colon) that underwent EMR were analyzed. The overall rate of CSPEB was 6.4 % (proximal 8.9 %; distal 3.7 %). Endoscopic management was required in 45 % of CSPEB episodes. With a clip distance of 3 mm, the expected cost of prophylactic clipping was € 1106 per lesion compared with € 157 per lesion for the expected cost of CSPEB without clipping. At 100 % clipping efficacy, the FNS was € 14 826 (proximal and distal lesions € 9309 and € 29 540, respectively). A clip price of € 10.35 was required for the cost of clipping to offset the cost of CSPEB. A prophylactic clipping strategy is not cost-effective and at present cannot be justified for all lesions or selectively for lesions in the proximal colon. ClinicalTrials.gov (NCT01368289). © Georg Thieme Verlag KG Stuttgart · New York.

Decision making regarding prophylactic mastectomy: stability of preferences and the impact of anticipated feelings of regret.

NARCIS (Netherlands)

Dijk, S. van; Roosmalen, M.S van; Otten, W.; Stalmeier, P.F.M.

2008-01-01

PURPOSE: Women who test positive for a BRCA1/2 mutation face difficult choices to manage their breast cancer risk; one of these choices is whether to opt for prophylactic mastectomy. Few data are available about this decision-making process. The current study provides data regarding the stability of

Acute caries following radiation therapy in the nose/throat region. Prophylactic measures

Energy Technology Data Exchange (ETDEWEB)

Roella, G; Johansen, E [Oslo Univ. (Norway); Pedersen, K N [Rochester Univ., NY (USA)

1978-05-10

Recent research indicates that xerostomia caused by irradiation of the salivary glands causes rampant caries by inducing a soft sucrose rich diet in this group of patients and by reduction of the buffer capacity and volume of the secretion. Whereas total extraction of the teeth before the irradiation started was previously the normal procedure in these patients, the teeth now can be maintained by very simple and inexpensive prophylactic measures, involving use of a gel containing 1% of soldium fluoride for 5 minutes once daily.

New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

Directory of Open Access Journals (Sweden)

Robert H E Friesen

2010-02-01

Full Text Available The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.

Prophylactic total gastrectomy in hereditary diffuse gastric cancer

DEFF Research Database (Denmark)

Bardram, Linda; Hansen, Thomas V O; Gerdes, Anne-Marie

2014-01-01

Inactivating mutations in the CDH1 (E-cadherin) gene are the predisposing cause of gastric cancer in most families with hereditary diffuse gastric cancer (HDGC). The lifetime risk of cancer in mutation positive members is more than 80 % and prophylactic total gastrectomy is recommended. Not all...... mutations in the CDH1 gene are however pathogenic and it is important to classify mutations before this major operation is performed. Probands from two Danish families with gastric cancer and a history suggesting HDGC were screened for CDH1 gene mutations. Two novel CDH1 gene mutations were identified....... Hospital stay was 6-8 days and there were no complications. Small foci of diffuse gastric cancer were found in all patients-intramucosal in six and advanced in one. Preoperative endoscopic biopsies had revealed a microscopic cancer focus in two of the patients. Our data confirmed the pathogenic nature...

Status of prophylactic and therapeutic genital herpes vaccines.

Science.gov (United States)

Awasthi, Sita; Friedman, Harvey M

2014-06-01

A half billion people have genital herpes infections worldwide. Approximately one-fifth of American women between ages 14 and 49 are HSV-2 seropositive. The development of an effective genital herpes vaccine is a global health necessity based on the mental anguish genital herpes causes for some individuals, the fact that pregnant women with genital herpes risk transmitting infection to their newborn children, and the observation that HSV-2 infection is associated with a 3-fold to 4-fold increased probability of HIV acquisition. We review the strengths and limitations of preclinical animal models used to assess genital herpes vaccine candidates and the goals of prophylactic and therapeutic vaccines. We also discuss the current pipeline of vaccine candidates and lessons learned from past clinical trials that serve as a stimulus for new strategies, study designs and endpoint determinations. Copyright © 2014 Elsevier B.V. All rights reserved.

Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice

International Nuclear Information System (INIS)

Nakada, Shinichiro

2016-01-01

The E3 ubiquitin ligases ring finger protein (RNF) 8 and RNF168 transduce the DNA double-strand break (DSB) response (DDR) signal by ubiquitinating DSB sites. The depletion of RNF8 or RNF168 suppresses the accumulation of DNA-repair regulating factors such as 53BP1 and RAP80 at DSB sites, suggesting roles for RNF8- and RNF168-mediated ubiquitination in DSB repair. This mini-review provides a brief overview of the RNF8- and RNF168-dependent DDR-signaling and DNA-repair pathways. The choice of DNA-repair pathway when RNF8- and RNF168-mediated ubiquitination-dependent DDR signaling is negatively regulated by deubiquitinating enzymes (DUBs) is reviewed to clarify how the opposing roles of RNF8/RNF168 and DUBs regulate ubiquitination-dependent DDR signaling and the choice of DNA-repair pathway

Prophylactic use of Saccharomyces boulardii probiotics in preventing antibiotic-associated diarrhea: a single center hospital-based case-control study in Serbia

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Nikola Panic

2015-12-01

Full Text Available Background. Antibiotic-associated diarrhea (AAD develops through the loss of normal bacterial intestinal flora. We have conducted a case-control study in order to assess whether prophylactic administration of Saccharomyces boulardii (S. boulardii prevents occurrence of AAD among adult hospitalized patients. Methods. Single-center hospital based case-control study was conducted in University Clinic “Dr Dragisa Misovic-Dedinje”, Belgrade, Serbia. Hospital records were screened in order to identify all the patients developing AAD in period January 1. 2010 – August 31. 2015. For every case, one age and gender matched control was randomly selected among patients hospitalized at the same time at the same department who were administered with antibiotics and did not develop AAD. For both cases and controls data were extracted on demographics, medical history, indication for use of antibiotics, antibiotics used, and prophylactic use of S.boulardii probiotics. The relationship between occurrence of AAD and putative risk factors were measured using the odds ratios (ORs and their 95% confidence interval (CI derived from logistic regression analysis. Results. Number of 59 cases and 59 controls were included in the study. Most of AAD cases were associated with old age (mean age of 78.05, and almost half (49.15% were hospitalized on geriatrics department. Most prescribed class of antibiotics among cases was III generation cephalosporins (50.85%, followed by fluoroquinolones (28.81% and trimethoprim-sulfamethoxazole (20.34%. Significantly more cases than controls were treated with carbapenems (16.95% vs. 5.08% respectively, p=0.04. Significantly less cases were administered with prophylactic S. boulardii probiotics (18.64% vs. 42.37% p=0.005. We identified prophylactic use of S. boulardii to act protectively against development of AAD from both univariate (OR: 0.31, 95% CI: 0.14-0.72 and multivariate analysis (OR:0.36, 95% CI: 0.14-0.80. Use of

Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases

International Nuclear Information System (INIS)

Ohguri, Takayuki; Imada, Hajime; Kohshi, Kiyotaka; Kakeda, Shingo; Ohnari, Norihiro; Morioka, Tomoaki; Nakano, Keita; Konda, Nobuhide; Korogi, Yukunori

2007-01-01

Purpose: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). Methods and Materials: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). Radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. Results: Radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). Conclusions: The present study showed a potential value of prophylactic HBO for Radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit

Paracetamol as a prophylactic analgesic for hysterosalpingography: A double blind randomized controlled trial

International Nuclear Information System (INIS)

Elson, E.M.; Ridley, N.T.F.

2000-01-01

AIM: To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG). DESIGN: A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded. RESULTS: Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations. CONCLUSION: Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic

Paracetamol as a prophylactic analgesic for hysterosalpingography: A double blind randomized controlled trial

Energy Technology Data Exchange (ETDEWEB)

Elson, E.M.; Ridley, N.T.F

2000-09-01

AIM: To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG). DESIGN: A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded. RESULTS: Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations. CONCLUSION: Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic

Role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae

International Nuclear Information System (INIS)

Laukkanen, E.; Klonoff, H.; Allan, B.; Graeb, D.; Murray, N.

1988-01-01

Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of posttreatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated

Prophylactic antibiotic treatment in severe acute ischemic stroke: the Antimicrobial chemopRrophylaxis for Ischemic STrokE In MaceDonIa-Thrace Study (ARISTEIDIS).

Science.gov (United States)

Tziomalos, Konstantinos; Ntaios, George; Miyakis, Spiros; Papanas, Nikolaos; Xanthis, Andreas; Agapakis, Dimitrios; Milionis, Haralampos; Savopoulos, Christos; Maltezos, Efstratios; Hatzitolios, Apostolos I

2016-10-01

Infections represent a leading cause of mortality in patients with acute ischemic stroke, but it is unclear whether prophylactic antibiotic treatment improves the outcome. We aimed to evaluate the effects of this treatment on infection incidence and short-term mortality. This was a pragmatic, prospective multicenter real-world analysis of previously independent consecutive patients with acute ischemic stroke who were >18 years, and who had at admission National Institutes of Health Stroke Scale (NIHSS) >11. Patients with infection at admission or during the preceding month, with axillary temperature at admission >37 °C, with chronic inflammatory diseases or under treatment with corticosteroids were excluded from the study. Among 110 patients (44.5 % males, 80.2 ± 6.8 years), 31 (28.2 %) received prophylactic antibiotic treatment, mostly cefuroxime (n = 21). Prophylactic antibiotic treatment was administered to 51.4 % of patients who developed infection, and to 16.4 % of patients who did not (p antibiotic treatment (RR 5.84, 95 % CI 2.03-16.79, p antibiotic treatment did not differ between patients who died during hospitalization and those discharged, or between patients who died during hospitalization or during follow-up and those who were alive 3 months after discharge. Prophylactic administration of antibiotics in patients with severe acute ischemic stroke is associated with an increased risk of infection during hospitalization, and does not affect short-term mortality risk.

Prophylactic ketoconazole shampoo for tinea capitis in a high-risk pediatric population.

Science.gov (United States)

Bookstaver, P Brandon; Watson, Holly J; Winters, Shauna D; Carlson, Adrian L; Schulz, Richard M

2011-07-01

Although topical agents for the treatment of tinea capitis decrease viable fungal elements and reduce shedding, their use as a prophylactic agent has not been investigated. This study evaluated the effectiveness of a prophylactic ketoconazole shampoo (Nizoral 2%) protocol to reduce the number of clinically evident tinea capitis infections in a high-risk African American, urban population. We conducted a retrospective analysis of a ketoconazole prophylaxis protocol that was implemented at an urban pediatric clinic for medically fragile children. Patients at high risk for tinea capitis received twice-weekly ketoconazole shampoo. The primary outcome of the study was a reduction in the number of documented tinea capitis infections between the 12-month preprotocol and 12-month postprotocol periods. A secondary outcome included the evaluation of predisposing risk factors for acquiring tinea infections. Ninety-seven patients, with a mean age of 8.06 years, were included. Most patients (78%) were African American. There were a total of 13 tinea capitis infections during the 12-month preprotocol period. During the 12-month postprotocol period, 41 infections were documented: 37 (90.2%) in the prophylaxis group and 4 (9.8%) in the nonprophylaxis group. The average numbers of per-patient infections in the postprotocol period were 0.79 and 0.08 in the prophylaxis and nonprophylaxis groups, respectively. Initiation of prophylaxis did not reduce tinea capitis infections (p=NS). Previous history of infection and a high level of care were significant predictors of infections (pshampoo) prophylaxis protocol.

Long-Term Outcome and Complications Following Prophylactic Laparoscopic-Assisted Gastropexy in Dogs.

Science.gov (United States)

Loy Son, Natasha K; Singh, Ameet; Amsellem, Pierre; Kilkenny, Jessica; Brisson, Brigitte A; Oblak, Michelle L; Ogilvie, Adam T

2016-11-01

To characterize the short- and long-term outcome (>12 months), complications, and owner satisfaction following prophylactic laparoscopic-assisted gastropexy (LAG) in dogs. Retrospective study. Client-owned dogs (n = 49). Dogs that underwent prophylactic LAG at 2 veterinary academic hospitals were studied. Surgical time, anesthesia time, concurrent intra- and extra-abdominal procedures, and intraoperative and postoperative complications were recorded following review of medical records. Veterinarian and/or owner follow-up was obtained to determine outcome and satisfaction with LAG. Five of 49 dogs (10%) experienced complications related to abdominal access during LAG. Four percent (2/49) of dogs experienced an intraoperative complication. Follow-up information was available for 89% of dogs (44/49). Four dogs died of causes unrelated to LAG or gastric dilatation volvulus (GDV) in the follow-up period. Two dogs experienced major postoperative complications requiring additional veterinary intervention. Thirty percent (13 dogs) experienced a minor postoperative self-limiting wound-related complication. Median follow-up time was 698 days (range, 411-1825). No dogs experienced GDV. One hundred percent of dog owners were satisfied with LAG, would repeat the procedure in a future pet, and would recommend the procedure to a friend or family member. LAG was an effective procedure for prevention of GDV and was associated with high client satisfaction in this cohort of dogs. A moderate rate of postoperative wound complications occurred that were minor and self-limiting in nature. © Copyright 2016 by The American College of Veterinary Surgeons.

Roles of HMGA proteins in cancer: Expression, pathways, and redundancies

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Giancotti V

2016-10-01

Full Text Available The expression of the High Mobility Group A (HMGA proteins, their participation in cancer signalling pathways, and their redundant functions have been reviewed in seven types of cancer: breast, colorectal, prostate, lung, ovarian, thyroid, and brain. The analysis of cell lines and tumours revealed an elevated level of their expression in all fully transformed cancer systems, which represents a step of the main cancer signalling pathways. In breast, colorectal, prostate, and lung cancers Wnt/β-catenin pathway is a master inducer of cell transformation in which are deeply involved HMG A1 and A2 proteins. On the other hand, IL-6/Stat3 pathway is responsible for cancer transformation in breast, lung, and prostate. The expression of HMGA1 in lung and ovarian cancers is due to an active PI3K/Akt pathway. The let-7 family of microRNA represses the expression of HMGA showing specificity by its different forms: the let-7b form is able to inhibit both proteins A1 and A2, the last also inhibited by a, c, d, and g forms. Moreover, both proteins are down-regulated by the repressor couple p53/microRNA-34a. The protein A1 and A2 participate to the Epithelial-Mesenchymal Transition cooperating with the three couples of factors Twist1/2, Snai1/2, and Zeb1/2. Through a combination of pathways, there is the simultaneous presence of high levels of both A1 and A2 together with the expression of other factors: a high co-operating efficiency is reached that supplies the tumour cells with properties of self-renewal, resistance, and invasiveness.

The role of mass transport pathway in wormholelike mesoporous carbon for supercapacitors.

Science.gov (United States)

Liang, Yeru; Liang, Fengxue; Li, Zhenghui; Wu, Dingcai; Yan, Fangyu; Li, Siyu; Fu, Ruowen

2010-09-28

In the present paper, we demonstrate the importance of the role of a mass transport pathway (MTP) in wormholelike mesoporous carbon (WMC) through studying the ion diffusion behaviors within two different wormholelike mesopore networks with and without MTP. Our results reveal that the introduction of MTP is very helpful in improving ion diffusion properties. The as-prepared WMC with a MTP of ca. 9.7 nm exhibits notably better electric double layer performance as compared to the conventional WMC without a MTP. For example, even at the quick sweep rate of 50 mV s(-1), the surface specific capacitance of the former is 21.6 microF cm(-2), which is almost 4 times as high as that of the latter (5.5 microF cm(-2)).

A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining

DEFF Research Database (Denmark)

Grabarz, Anastazja; Guirouilh-Barbat, Josée; Barascu, Aurelia

2013-01-01

The choice of the appropriate double-strand break (DSB) repair pathway is essential for the maintenance of genomic stability. Here, we show that the Bloom syndrome gene product, BLM, counteracts CtIP/MRE11-dependent long-range deletions (>200 bp) generated by alternative end-joining (A-EJ). BLM...... represses A-EJ in an epistatic manner with 53BP1 and RIF1 and is required for ionizing-radiation-induced 53BP1 focus assembly. Conversely, in the absence of 53BP1 or RIF1, BLM promotes formation of A-EJ long deletions, consistent with a role for BLM in DSB end resection. These data highlight a dual role...... for BLM that influences the DSB repair pathway choice: (1) protection against CtIP/MRE11 long-range deletions associated with A-EJ and (2) promotion of DNA resection. These antagonist roles can be regulated, according to cell-cycle stage, by interacting partners such as 53BP1 and TopIII, to avoid...

Prophylactic use of antimicrobials in surgical pig models; a literature review (2012-2014).

Science.gov (United States)

Bradbury, A G; Argyle, S; Eddleston, M; Clutton, R E

2015-07-04

There are no guidelines for antimicrobial use in experimental animals even though appropriate selection is required to reduce risk of surgical site infection (SSI) and resistance development. Pigs are used extensively as experimental surgical models for people. This review compares reported antimicrobial prescription in recently published pig surgical studies (retrieved by PubMed, Web of Knowledge and Google Scholar) with human guidelines for prophylactic antimicrobial use (National Institute of Clinical Excellence and the American Society of Health-System Pharmacists). A five-point appropriate antimicrobial use index (AAUI), based on aforementioned guidelines, was used to grade 233 studies. Use of World Health Organization-designated critically important antimicrobials (CIA) was recorded. Antimicrobial use was described in 111 of 233 (48 per cent) papers. AAUI scores of 5 (maximal compliance) and 0 (no compliance) were awarded to 34 (15 per cent) and 101 (43 per cent) articles. Where reported, prophylactic antimicrobials were mostly administered after surgery (62/95, 65 per cent) and intramuscularly (36/72, 50 per cent). CIAs were described in 21 of 111 (19 per cent) papers and SSIs in 21 of 233 (9 per cent). Reported antimicrobial prophylaxis in experimental pig surgery deviates from human clinical guidelines. This has implications for antimicrobial resistance, study quality and animal welfare. Until species-specific guidelines are formulated, experimental surgical studies involving animals would probably benefit from adherence to human guidelines. British Veterinary Association.

Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer?

Science.gov (United States)

Kopelman, Tammy R; O'Neill, Patrick J; Pieri, Paola G; Salomone, Jeffrey P; Hall, Scott T; Quan, Asia; Wells, Jordan R; Pressman, Melissa S

2013-12-01

Inadequate anti-factor Xa levels and increased venous thromboembolic events occur in trauma patients receiving standard prophylactic enoxaparin dosing. The aim of this study was to test the hypothesis that higher dosing (40 mg twice daily) would improve peak anti-Xa levels and decrease venous thromboembolism. A retrospective review was performed of trauma patients who received prophylactic enoxaparin and peak anti-Xa levels over 27 months. Patients were divided on the basis of dose: group A received 30 mg twice daily, and group B received 40 mg twice daily. Demographics and rates of venous thromboembolism were compared between dose groups and patients with inadequate or adequate anti-Xa levels. One hundred twenty-four patients were included, 90 in group A and 34 in group B. Demographics were similar, except that patients in group B had a higher mean body weight. Despite this, only 9% of group B patients had inadequate anti-Xa levels, compared with 33% of those in group A (P = .01). Imaging studies were available in 69 patients and revealed 8 venous thromboembolic events (P = NS, group A vs group B) with significantly more venous thromboembolic events occurring in patients with low anti-Xa levels (P = .02). Although higher dosing of enoxaparin led to improved anti-Xa levels, this did not equate to a statistical decrease in venous thromboembolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi.

Directory of Open Access Journals (Sweden)

Haijun Xu

2010-09-01

Full Text Available Borrelia burgdorferi, the Lyme disease spirochete, dramatically alters its transcriptome and proteome as it cycles between the arthropod vector and mammalian host. During this enzootic cycle, a novel regulatory network, the Rrp2-RpoN-RpoS pathway (also known as the σ(54-σ(S sigma factor cascade, plays a central role in modulating the differential expression of more than 10% of all B. burgdorferi genes, including the major virulence genes ospA and ospC. However, the mechanism(s by which the upstream activator and response regulator Rrp2 is activated remains unclear. Here, we show that none of the histidine kinases present in the B. burgdorferi genome are required for the activation of Rrp2. Instead, we present biochemical and genetic evidence that supports the hypothesis that activation of the Rrp2-RpoN-RpoS pathway occurs via the small, high-energy, phosphoryl-donor acetyl phosphate (acetyl∼P, the intermediate of the Ack-Pta (acetate kinase-phosphate acetyltransferase pathway that converts acetate to acetyl-CoA. Supplementation of the growth medium with acetate induced activation of the Rrp2-RpoN-RpoS pathway in a dose-dependent manner. Conversely, the overexpression of Pta virtually abolished acetate-induced activation of this pathway, suggesting that acetate works through acetyl∼P. Overexpression of Pta also greatly inhibited temperature and cell density-induced activation of RpoS and OspC, suggesting that these environmental cues affect the Rrp2-RpoN-RpoS pathway by influencing acetyl∼P. Finally, overexpression of Pta partially reduced infectivity of B. burgdorferi in mice. Taken together, these findings suggest that acetyl∼P is one of the key activating molecule for the activation of the Rrp2-RpoN-RpoS pathway and support the emerging concept that acetyl∼P can serve as a global signal in bacterial pathogenesis.

Can serological methods help distinguish between prophylactic and alloimmune anti-D?

Science.gov (United States)

Irving, C; Crennan, M; Vanniasinkam, T

2017-10-01

Enzyme indirect antiglobulin test (EIAT) and polyethylene glycol IAT (PIAT) were evaluated for their potential use as tests to distinguish between prophylactic and alloimmune anti-D in plasma by comparing with a tube variation of the standard low ionic strength solution-IAT (LISS-IAT). Laboratories performing the screening of RhD-negative pregnant women are required to provide clinicians with guidance as to the source of detected RhD antibodies. Currently, this is derived from RhIg immunoprophylaxis history, agglutination scores and titration results, where performed. A serological test that can differentiate between prophylactic and alloimmune anti-D would be useful in the diagnosis of RhD alloimmunisation in pregnant women. Plasma samples (n = 273) [fresh (collected from April 2014 to February 2015) and frozen (up to 2 years)] from antenatal females, preoperative males and females over child-bearing age were used in this study. Samples were identified as containing anti-D by routine column agglutination (CAT) and were tested by tube LISS-IAT, EIAT and PIAT, and a score difference was calculated. A total of 32% of alloimmune anti-D samples demonstrated an increase in agglutination score (+2 or +3) when tested by EIAT. A significant increase in agglutination score for alloimmune samples using EIAT compared with LISS-IAT was observed. EIAT had a sensitivity (Sn) of 59%, positive predictive value (PPV) of 100% and specificity (Sp) of 100% for alloimmune anti-D. EIAT is capable of confirming but not excluding the presence of alloimmune anti-D in samples where anti-D is detected in routine antibody screening. © 2017 British Blood Transfusion Society.

Posterior epistaxis: Common bleeding sites and prophylactic electrocoagulation.

Science.gov (United States)

Liu, Juan; Sun, Xicai; Guo, Limin; Wang, Dehui

2016-01-01

Posterior epistaxis is a frequent emergency, and the key to efficient management is identification of the bleeding point. We performed a retrospective study of 318 patients with posterior epistaxis treated with endoscopic bipolar electrocautery during a 4-year period. Distribution of the bleeding sites was recorded. Patients with no definite bleeding sites in the first operation were assigned to Group A (n = 39) and Group B (n = 34). Patients in Group A were only observed in the ward. Patients in Group B were given prophylactic electrocoagulation at the common bleeding points. Of the 318 patients, bleeding sites were successfully identified and coagulated in 263 patients. All of them were located posteriorly, with 166 on the lateral nasal wall, 86 on the septum, and 11 on the anterior face of the sphenoid sinus. The rebleeding rate of Group B (8.8%) was lower than that of Group A (38.5%) (p < 0.01).

Super selective transcatheter angiographic embolization: an effective and prophylactic treatment for massive obstetric haemorrhage

International Nuclear Information System (INIS)

Zhou Yiming; Zhai Renyou; Qian Xiaojun; Wei Baojie; Gao Kun; Zhang Shilong; Liu Jinmei; Zhang Qiuhong; Jiang Lei

2008-01-01

Objective: To discuss the effect and safety of transcatheter angiographic embolization (TAE)for managing massive obstetric haemorrhage. Methods: 17 cases of obstetric massive haemorrhage or with haemorrhage tendency were treated with TAE. Among them 14 cases had haemorrhage already, including 10 cases after abortion, caesarean section or normal labor and other 4 of hydatidiform mole. 3 cases with obstetric haemorrhage tendency included 2 cases of placenta praevia and 1 case of cervical pregnancy. Selective catheterization into bilateral uterine arteries or internal iliac arteries for DSA, showed the cause and location of the haemorrhage and then embolized with gelfoam sponge chips (1-3 mm) or Polyvinyl Alcohol(PVA); and part of the cases with MTX through uterine arterial perfusion. Results: The successful rate of catheterization was 100%. The achievement in 14 cases showed no active haemorrhage immediately after the procedure and no vaginal bleeding after 1-5 days. In 3 prophylactic cases before abortion or uterine curettage, obstetric massive haemorrhage occurred in 1 case, but not so in other 2 cases. Conclusions: TAE is an effective treatment for obstetric massive haemorrhage, with the advantages of minimal trauma, fast and definite treating effect and less complications. Prophylactical application for high risk patients can reduce the bleeding and mortality. (authors)

Analgesic effectiveness of prophylactic therapy and continued therapy with naproxen sodium post simple extraction.

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Angel Asmat-Abanto

2015-02-01

Full Text Available To compare the analgesic effectiveness of the prophylactic therapy and continued therapy with naproxen sodium after a simple dental extraction. Material and methods: This prospective randomized, parallel, single-blind clinical trial was developed in the Dental Clinic of the Universidad Alas Peruanas in Trujillo (Peru. The patients, who required simple extraction due to dental caries, were randomly distributed into three groups: 30 of them took 550mg naproxen sodium in the preoperative period and then every 12 hours, other 30 took 550mg naproxen sodium in the postoperative period and then every 12 hours, and 30(control group, received 400mg ibuprofen in the postoperative period and then every 8 hours, depending on the established criteria. The procedure was standardized, analgesic effectiveness was assessed by visual analog scale and the presence of adverse drug reactions was evaluated as well. Data were analyzed using ANOVA and Duncan’s test using IBM SPSS 22 with a significance level of 5%. Results: Continued therapy with naproxen sodium showed greater analgesic effectiveness after a simple extraction at 1, 8 and 24 hours (p<0.005. Conclusion: Continued therapy with naproxen sodium presented greater effectiveness than prophylactic therapy with naproxen sodium after a simple extraction.

Prophylactic immunization against experimental leishmaniasis. III. Protection against fatal Leishmania tropica infection induced by irradiated promastigotes involves Lyt-1+2- T cells that do not mediate cutaneous DTH

International Nuclear Information System (INIS)

Liew, F.Y.; Howard, J.G.; Hale, C.

1984-01-01

Protective immunity against fatal L. tropica infection in genetically vulnerable BALB/c mice can be induced by prophylactic immunization with irradiated promastigotes even when heat-killed. Such immunity is adoptively transferable transiently into intact or durably into sub-lethally irradiated (200 or 550 rad) syngeneic recipients by splenic T but not B cells. The effector T cells are of the Lyt-1 + 2 - phenotype, devoid of demonstrable cytotoxic activity. The immune splenic T cell population expresses specific helper activity for antibody synthesis. A causal role for helper T cells in this capacity, however, seems unlikely, because it was shown that antibody does not determine the protective immunity against L. tropica. The immunized donors show no detectable cutaneous DTH or its early memory recall in response to live or killed promastigotes or a soluble L. tropica antigen preparation. Spleen, lymph node, and peritoneal exudate cells from protectively immunized donors similarly fail to transfer DTH locally or systemically. These cells also lack demonstrable suppressive activity against the expression or induction of DTH to L. tropica. Thus, protection against L. tropica induced by prophylactic i.v. immunization with irradiated promastigotes appears to be conferred by Lyt-1 + 2 - T cells that are distinguishable from T cells mediating either both DTH and T help, or cytotoxicity

Prophylactic radiotherapy of the breast in patients with prostatic carcinoma before application of contrasexual hormones

Energy Technology Data Exchange (ETDEWEB)

Arndt, D.; Heibel, J.H.

1983-08-01

Symptoms and objective parameters of gynecomastia are analysed in 113 patients, who received prophylactic irradiation of the breast (12 Gy in 3 fractions) prior to estrogen therapy of prostatic carcinoma. Another 10 patients were treated equally after estrogens had caused severe complaints. Symptoms increased from 10% to 100% in relation to 4 classes of gynecomastia. They were mild in 27.5%, moderate in 23.9% and severe in 8.8%. A correlation between metric classification and graded symptoms became more evident when only 2 groups were distinguished. With a maximum diameter of 3.5 cm only 17% of the patients had mostly slight discomfort in contrast to 70% of the patients with a gland of more than 3.5 cm in diameter; they revealed moderate or serious complaints. These results indicate that prophylactic radiotherapy may reduce severe complications to less than 10% as compared to 70-80% without irradiation. If gynecomastia has developed, regression by subsequent radiotherapy seems to be impossible; but the intensity of complaints could be reduced in our ten patients. Provided that irradiation precedes estrogen application, this sequence may be considered as a reasonable alternative to expensive antiandrogen therapy.

Inhibition of Inflammation Mediated Through the Tumor Necrosis Factor α Biochemical Pathway Can Lead to Favorable Outcomes in Alzheimer Disease.

Science.gov (United States)

Shamim, Daniah; Laskowski, Michael

2017-01-01

Tumor necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. This article extensively reviewed literature on animal studies testing these agents. The results showed a role for direct and indirect TNF-α inhibition through agents such as thalidomide, 3,6-dithiothalidomide, etanercept, infliximab, exendin-4, sodium hydrosulfide, minocycline, imipramine, and atorvastatin. Studies were performed on mice, rats, and monkeys, with induction of neurodegenerative physiology either through the use of chemical agents or through the use of transgenic animals. Most of these agents showed an improvement in cognitive function as tested with the Morris water maze, and immunohistochemical and histopathological staining studies consistently showed better outcomes with these agents. Brains of treated animals showed significant reduction in pro-inflammatory TNF-α and reduced the burden of neurofibrillary tangles, amyloid precursor protein, and β-amyloid plaques. Also, recruitment of microglial cells in the central nervous system was significantly reduced through these drugs. These studies provide a clearer mechanistic understanding of the role of TNF-α modulation in Alzheimer disease. All studies in this review explored the use of these drugs as prophylactic agents to prevent Alzheimer disease through immune modulation of the TNF inflammatory pathway, and their success highlights the need for further research of these drugs as therapeutic agents.

Identifying pathways affected by cancer mutations.

Science.gov (United States)

Iengar, Prathima

2017-12-16

Mutations in 15 cancers, sourced from the COSMIC Whole Genomes database, and 297 human pathways, arranged into pathway groups based on the processes they orchestrate, and sourced from the KEGG pathway database, have together been used to identify pathways affected by cancer mutations. Genes studied in ≥15, and mutated in ≥10 samples of a cancer have been considered recurrently mutated, and pathways with recurrently mutated genes have been considered affected in the cancer. Novel doughnut plots have been presented which enable visualization of the extent to which pathways and genes, in each pathway group, are targeted, in each cancer. The 'organismal systems' pathway group (including organism-level pathways; e.g., nervous system) is the most targeted, more than even the well-recognized signal transduction, cell-cycle and apoptosis, and DNA repair pathway groups. The important, yet poorly-recognized, role played by the group merits attention. Pathways affected in ≥7 cancers yielded insights into processes affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnocellular pathway for rotation invariant Neocognitron.

Science.gov (United States)

Ting, C H

1993-03-01

In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

The TLR13-MyD88-NF-κB signalling pathway of Cyclina sinensis plays vital roles in innate immune responses.

Science.gov (United States)

Ren, Yipeng; Ding, Dan; Pan, Baoping; Bu, Wenjun

2017-11-01

Toll-like receptors, the best known pattern recognition receptors, play important roles in recognizing non-self molecules and binding pathogen-associated molecular patterns in the innate immune system. In the present research, the cDNA and protein characterization of the TLR signalling pathway genes including IRAK4, TRAK6 and IKKα (named CsIRAK4, CsTRAF6 and CsIKKα, respectively) with the typical motifs from Cyclina sinensis showed significant similarity with their homologues from other shellfish. Furthermore, the mRNA transcripts of these three genes are ubiquitously expressed in all tissues tested and are dominantly expressed in C. sinensis haemocytes (P sinensis by RNA interference and immune challenges. The results suggested the mRNA expression patterns of CsMyD88, CsIRAK4, CsTRAF6, CsIKKα, CsIκB, CsNF-κB, CsC-LYZ and CsAMP were all down-regulated (P sinensis haemocytes, revealing the involvement of the TLR13-MyD88-NF-κB signalling pathway in innate immunity by positively adjusting internal signalling factors and immune-related genes. In summary, a TLR13-MyD88-NF-κB signalling pathway exists and plays vital roles in innate immune responses in C. sinensis. These findings collectively lay the foundation for studying the functional characterization of internal signalling factors and establishing a regulatory network for the TLR signalling pathway in molluscs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disability, anxiety and depression associated with medication-overuse headache can be considerably reduced by detoxification and prophylactic treatment

DEFF Research Database (Denmark)

Bendtsen, L; Munksgaard, Sb; Tassorelli, C

2014-01-01

OBJECTIVE: The objective of this article is to investigate whether headache-related disability, depression and anxiety can be reduced by detoxification and prophylactic treatment in patients with medication-overuse headache (MOH). METHODS: Patients with MOH were included from six centres in Europ...

Impact of the prophylactic gastrostomy for unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy on quality of life: Prospective randomized trial

International Nuclear Information System (INIS)

Salas, Sebastien; Baumstarck-Barrau, Karine; Alfonsi, Marc; Digue, Laurence; Bagarry, Danielle; Feham, Nasreddine; Bensadoun, Rene Jean; Pignon, Thierry; Loundon, Anderson; Deville, Jean-Laurent; Zanaret, Michel; Favre, Roger; Duffaud, Florence; Auquier, Pascal

2009-01-01

Background and purpose: Concomitant radio-chemotherapy is the gold standard treatment for unresectable head and neck carcinomas. Placement of prophylactic gastrostomy has been proposed to provide adequate nutrition during the therapeutic sequence. The objectives of this study were to assess the impact of prophylactic gastrostomy on the 6-month quality of life, and to determine the factors related to this quality of life. Materials and methods: Design. randomized, controlled, open study ('systematic percutaneous gastrostomy' versus 'no systematic gastrostomy'). Patients. squamous cell head and neck carcinoma (stages III and IV, UICC 1997). Setting. oncological departments of French university teaching hospitals. Treatment. optimal concomitant radio-chemotherapy. Evaluations. T0 baseline evaluation, T1 during the treatment, T2 end of the treatment, and T3 6-month post-inclusion. Primary endpoint. 6-month quality of life (Qol) assessed using SF36, EORTC QLQ-C30, EORTC QLQ H and N35 questionnaires. Results: The Qol changes from baseline included a decline (T1 and T2) followed by an improvement (T3). Qol at 6 months was significantly higher in the group receiving systematic prophylactic gastrostomy (p = 10 -3 ). Higher initial BMI and lower initial Karnofsky index were significant factors related to a higher 6-month Qol. Conclusions: The study results suggest that prophylactic gastrostomy improves post-treatment quality of life for unresectable head and neck cancer patients, after adjusting for other potential predictive quality of life factors.

Realities of the prophylactic health care of workers in Poland

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Jerzy A. Kopias

2015-12-01

Full Text Available Background: The Polish occupational health system (OHS, existing over the past 17 years, has recently been contested as never before. Critical voices pertain to both legislative and executive aspects of the system, in which key roles are played by employers and occupational medicine service. There are some reasons for making a hypothesis that relevant norms are not always respected by the main actors. Material and methods: The data on the observance of norms by entities responsible for providing workers with prophylactic health care were analyzed. They were obtained from the existing external resources and materials collected during the implementation of tasks assigned by the Ministry of Health. Results: Legal norms, which constitute OHS in Poland are generally neither respected by the employers, nor by the representatives of occupational medicine service. Nearly half (45–47% of employers infringe provisions relating to medical examinations of workers. Such a degree of non-observance of respective laws would have not been the case if it was not for the attitudes and “silent approval” of many (but not all occupational physicians. Laws defining the responsibilities of occupational medicine service units on one hand, and of employers on the other, are for many reasons infringed by both groups. Conclusions: The data analyses indicate that the Polish OHS is, to a large extent, not acceptable and should be replaced with another one founded on other assumptions and responsive to contemporary occupational health challenges. New provisions should be formulated on the basis of merit and guided by socially accepted norms. Med Pr 2015;66(6:815–825

[Realities of the prophylactic health care of workers in Poland].

Science.gov (United States)

Kopias, Jerzy A

2015-01-01

The Polish occupational health system (OHS), existing over the past 17 years, has recently been contested as never before. Critical voices pertain to both legislative and executive aspects of the system, in which key roles are played by employers and occupational medicine service. There are some reasons for making a hypothesis that relevant norms are not always respected by the main actors. The data on the observance of norms by entities responsible for providing workers with prophylactic health care were analyzed. They were obtained from the existing external resources and materials collected during the implementation of tasks assigned by the Ministry of Health. Legal norms, which constitute OHS in Poland are generally neither respected by the employers, nor by the representatives of occupational medicine service. Nearly half (45-47%) of employers infringe provisions relating to medical examinations of workers. Such a degree of non-observance of respective laws would have not been the case if it was not for the attitudes and "silent approval" of many (but not all) occupational physicians. Laws defining the responsibilities of occupational medicine service units on one hand, and of employers on the other, are for many reasons infringed by both groups. The data analyses indicate that the Polish OHS is, to a large extent, not acceptable and should be replaced with another one founded on other assumptions and responsive to contemporary occupational health challenges. New provisions should be formulated on the basis of merit and guided by socially accepted norms. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

CONTRALATERAL PROPHYLACTIC MASTECTOMY AND SIMULTANEOUS BREAST RECONSTRUCTION WITH IMPLANTS AFTER ONE SIDED BREAST CANCER: ANALYSIS OF 12 CASES IN CONTEXT OF THE CURRENT TRENDS

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Roman Romansky

2016-08-01

Full Text Available The contemporary tendency for increase of prophylactic surgical procedures as part of the sophisticated treatment of breast cancer is the foundation for the present study. Evaluation of risk factors for developing contralateral breast cancer, factors for an increase in prophylactic mastectomies and indications for performing those operations are briefly commented. Analysis of 12 cases of the authors surgical practice is presented regarding treatment approach from the oncological, reconstructive and aesthetic point of view. Results, complications, alternative methods, clinical importance and possible future aspects are discussed.

Postoperative Complications After Prophylactic Thyroidectomy for Very Young Patients With Multiple Endocrine Neoplasia Type 2

Science.gov (United States)

Kluijfhout, Wouter P.; van Beek, Dirk-Jan; Verrijn Stuart, Annemarie A.; Lodewijk, Lutske; Valk, Gerlof D.; van der Zee, David C.; Vriens, Menno R.; Borel Rinkes, Inne H.M.

2015-01-01

Abstract The aim of this study was to investigate whether younger age at surgery is associated with the increased incidence of postoperative complications after prophylactic thyroidectomy in pediatric patients with multiple endocrine neoplasia (MEN) 2. The shift toward earlier thyroidectomy has resulted in significantly less medullary thyroid carcinoma (MTC)-related morbidity and mortality. However, very young pediatric patients might have a higher morbidity rate compared with older patients. Hardly any literature exists on complications in the very young. A retrospective single-center analysis was performed on the outcomes of MEN2 patients undergoing a prophylactic total thyroidectomy at the age of 17 or younger. Forty-one MEN2A and 3 MEN2B patients with thyroidectomy after January 1993 and at least 6 months of follow-up were included, subdivided in 9 patients younger than 3 years, 15 patients 3 to 6 years, and 20 patients older than 6 years. Postoperative hypocalcemia and other complications were registered. Twelve (27%) patients developed transient hypocalcemia and 9 (20%) patients suffered from permanent hypocalcemia, with a nonsignificant trend toward higher incidence with decreasing age. Three (7%) patients had other complications, of whom 2 were younger than 3 years. For patients younger than 3 years, the average length of stay (LOS) was 6.7 days, versus 1.7 and 3.5 days, respectively, for the older patient groups (P < 0.05). Patients with complications had a longer LOS compared with patients without (5.0 vs 2.0, P < 0.01). None of the patients had clinical signs of recurrent MTC after a mean follow-up of 10.5 years. Prophylactic thyroidectomy in very young children is associated with a higher rate of complications, causing a significant increased LOS. Irrespective age of surgery, MTC did not recur in any patient. In planning optimal timing of surgery, clinicians should take the risk of complications into account. We advise not to perform total

Crosstalk of Autophagy and the Secretory Pathway and Its Role in Diseases.

Science.gov (United States)

Zahoor, Muhammad; Farhan, Hesso

2018-01-01

The secretory and autophagic pathways are two fundamental, evolutionary highly conserved endomembrane processes. Typically, secretion is associated with biosynthesis and delivery of proteins. In contrast, autophagy is usually considered as a degradative pathway. Thus, an analogy to metabolic pathways is evident. Anabolic (biosynthetic) and catabolic (degradative) pathways are usually intimately linked and intertwined, and likewise, the secretory and autophagy pathways are intertwined. Investigation of this link is an emerging area of research, and we will provide an overview of some of the major advances that have been made to contribute to understanding of how secretion regulates autophagy and vice versa. Finally, we will highlight evidence that supports a potential involvement of the autophagy-secretion crosstalk in human diseases. © 2018 Elsevier Inc. All rights reserved.

Endoscopic Therapy of Refractory Post-Papillotomy Bleeding With Electrocautery Forceps Coagulation Method Combined With Prophylactic Pancreatic Stenting

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Zsolt Dubravcsik

2014-01-01

Conclusion: We presented a new, effective and safe second line endoscopic hemostatic method in patients with therapy resistant post-papillotomy bleeding. Combination of prophylactic pancreatic stenting and thermal coagulation with coagulation forceps might be suggested as a rescue treatment in patients with severe post-papillotomy bleeding, resistant to standard endoscopic therapy.

Quantitative trait loci and metabolic pathways

Science.gov (United States)

McMullen, M. D.; Byrne, P. F.; Snook, M. E.; Wiseman, B. R.; Lee, E. A.; Widstrom, N. W.; Coe, E. H.

1998-01-01

The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for “channeling” of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits. PMID:9482823

An In-vitro Study of the Load Deflection Characteristics of the Thermal Wires Immersed in Different Fluoride Prophylactic Agents

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Sami K. Al-Joubori

2018-04-01

Full Text Available Background: Fluoridated prophylactic agents have been reported to cause corrosion and discoloration of titanium alloys. Degradation in the mechanical properties lead to a decrease in a suitable orthodontic force, thereby causing delayed leveling of crooked teeth. This study was designed to evaluate the load deflection characteristics of thermal nickel titanium arch wires during unloading phase after ninety minutes immersion in three different fluoride agents. Material and methods: Forty specimens of thermal wires were obtained from Ortho Technology Company, which had 0.019” × 0.025” rectangular in cross section. Ten specimens from the wire size were immersed in one of the tested fluoride prophylactic agents (neutral sodium fluoride gel, stannous fluoride gel or Phos-Flur® mouth rinse or in the controlled medium of normal saline and incubated at 37°C for ninety minutes. A Wp 300 universal material testing machine was modified and used to perform a three-point bending test in a water path at 37 ± 1°C. The statistical difference between the different agents was analyzed using ANOVA and least significant difference tests. Results: The unloading forces at 0.5 mm, 1.0 mm, and 1.5 mm where significantly reduced especially in acidulated phosphate fluoride treated specimens followed by neutral fluoride treated specimens. Conclusion: Based on the results found in this study it can be preferred to use fluoride prophylactic agents with the least acidity and fluoride ions concentration.

Role of Notch signalling pathway in cancer and its association with ...

Indian Academy of Sciences (India)

The Notch signalling pathway is an evolutionarily conserved cell signalling pathway involved in the development of organ- ... Abnormal Notch signalling is seen in many cancers like T-cell acute ...... Morgan T. H. 1917 The theory of the gene.

Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli.

Science.gov (United States)

Yang, Chen; Gao, Xiang; Jiang, Yu; Sun, Bingbing; Gao, Fang; Yang, Sheng

2016-09-01

Isoprene, a key building block of synthetic rubber, is currently produced entirely from petrochemical sources. In this work, we engineered both the methylerythritol phosphate (MEP) pathway and the mevalonate (MVA) pathway for isoprene production in E. coli. The synergy between the MEP pathway and the MVA pathway was demonstrated by the production experiment, in which overexpression of both pathways improved the isoprene yield about 20-fold and 3-fold, respectively, compared to overexpression of the MEP pathway or the MVA pathway alone. The (13)C metabolic flux analysis revealed that simultaneous utilization of the two pathways resulted in a 4.8-fold increase in the MEP pathway flux and a 1.5-fold increase in the MVA pathway flux. The synergy of the dual pathway was further verified by quantifying intracellular flux responses of the MEP pathway and the MVA pathway to fosmidomycin treatment and mevalonate supplementation. Our results strongly suggest that coupling of the complementary reducing equivalent demand and ATP requirement plays an important role in the synergy of the dual pathway. Fed-batch cultivation of the engineered strain overexpressing the dual pathway resulted in production of 24.0g/L isoprene with a yield of 0.267g/g of glucose. The synergy of the MEP pathway and the MVA pathway also successfully increased the lycopene productivity in E. coli, which demonstrates that it can be used to improve the production of a broad range of terpenoids in microorganisms. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

[A prophylactic program for strain urinary incontinence].

Science.gov (United States)

Stadnicka, Grazyna; Iwanowicz-Palus, Grazyna J; Bień, Agnieszka M

2002-01-01

The aim of the study was to work out a prophylactic program for strain urinary incontinence. Analysis of literature on the subject and results of own investigations presented in the first part of the paper indicate that the program of prophylaxis of strain urinary incontinence should primarily include: (1) Preparation of the medical staff (nurses, midwives) for propagating health education among women on prevention of strain urinary incontinence. (2) Preparation of adequate educational materials in the form of brochures, leaflets, information posters about symptoms, causes and prophylaxis of urinary incontinence indicating health care institutions available to all women when the disease is suspected or already present. (3) Propagation of problems connected with strain urinary incontinence in the mass media providing information to a wide audience in order to make people realize the significance of this social problem and break stereotypes associated with this disease of "shame". (4) Preparation of sets of exercises for the muscles of the base of the pelvis to be performed during pregnancy, confinement and menopause to maintain their proper function. (5) Indicating factors predisposing to strain urinary incontinence with focus on possibilities of their reduction or elimination.

Prophylactic therapy with omeprazole for prevention of equine gastric ulcer syndrome (EGUS) in horses in active training: A meta-analysis.

Science.gov (United States)

Mason, L V; Moroney, J R; Mason, R J

2018-04-17

Guidelines regarding the impact and value of prophylaxis or maintenance therapy in equine gastric ulcer syndrome (EGUS) are not well-established or defined. The merits and the magnitude of effects of prophylaxis for spontaneous or recurrent squamous gastric ulceration in horses in training are uncertain. To pool data from randomised controlled trials (RCTs) to eliminate reporting bias and evaluate the efficacy of prophylactic omeprazole in the prevention of EGUS in training horses, and secondarily to compare prophylactic dosages of omeprazole. Meta-analysis. This meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search identified RCTs comparing omeprazole prophylaxis with sham in prevention of EGUS. Data were analysed using the Mantel-Haenszel test method to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Primary outcome was efficacy of prophylaxis. Secondary outcome was endoscopic severity of ulceration. The influence of study characteristics on the outcomes was examined by subgroup analyses. In preventing gastric ulcer occurrence, omeprazole prophylaxis was superior to sham in training horses (7 trials, 566 horses, RR 0.28, 95% CI 0.18-0.43; 23.4% in omeprazole prophylaxis vs. 77.2% in sham; high quality evidence). Prevalence of ulceration was 75.3 and 87.2% in the sham arms of the 1 mg/kg and 2 mg/kg omeprazole groups, respectively. Severity scores were significantly lower for omeprazole vs. sham (mean difference [MD] -1.05; 95% CI -1.35 to -0.69). Subgroup analyses comparing prophylactic omeprazole dosages resulted in a mean difference of -0.94 and -1.60 for the 1 and 2 mg/kg groups, respectively. Studies showed heterogeneity with regard to prophylactic dose. Omeprazole prophylaxis in active training horses significantly reduces gastric ulceration compared with no prophylaxis (sham) with the

Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

Institute of Scientific and Technical Information of China (English)

Hui Wang; Rui-Yun Peng

2016-01-01

With key roles in essential brain functions ranging from the long-term potentiation (LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor (NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca2+,postsynaptic density 95 (PSD-95),calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ),protein kinase A (PKA),mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.

The secret role of microRNAs in cancer stem cell development and potential therapy: A Notch-pathway approach.

Directory of Open Access Journals (Sweden)

Marianna eProkopi

2015-02-01

Full Text Available MicroRNAs (miRNAs have been implicated in the development of some if not all cancer types and have been identified as attractive targets for prognosis, diagnosis and therapy of the disease. MiRNAs are a class of small non-coding RNAs (20-22 nucleotides in length that bind imperfectly to the 3’-untranslated region of target mRNA regulating gene expression. Aberrantly expressed miRNAs in cancer, sometimes known as oncomiRNAs, have been shown to play a major role in oncogenesis, metastasis and drug resistance. Amplification of oncomiRNAs during cancer development correlates with the silencing of tumor suppressor genes; on the other hand, down-regulation of miRNAs has also been observed in cancer and cancer stem cells (CSCs. In both cases, miRNA regulation is inversely correlated with cancer progression. Growing evidence indicates that miRNAs are also involved in the metastatic process by either suppressing or promoting metastasis-related genes leading to the reduction or activation of cancer cell migration and invasion processes. In particular, circulating miRNAs (vesicle-encapsulated or non-encapsulated have significant effects on tumorigenesis: membrane-particles, apoptotic bodies and exosomes have been described as providers of a cell-to-cell communication system transporting oncogenic miRNAs from tumors to neighboring cells and distant metastatic sites. It is hypothesized that MiRNAs control cancer development in a traditional manner, by regulating signaling pathways and factors. In addition, recent developments indicate a non-conventional mechanism of cancer regulation by stem cell reprogramming via a regulatory network consisting of miRNAs and Wnt/β-catenin, Notch, and Hedgehog signaling pathways, all of which are involved in controlling stem cell functions of CSCs. In this review, we focus on the role of miRNAs in the Notch pathway and how they regulate CSC self-renewal, differentiation and tumorigenesis by direct/indirect targeting of

Prophylactic Granisetron Vs Pethidine for the Prevention of Postoperative Shivering: A Randomized Control Trial

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Asif lqbal

2009-01-01

The three groups did not differ significantly regarding patient characteristics. The numbers of patients shivering on arrival in the recovery room at 15 minutes after operation were significantly less in Group P (7% and Group G (17% than in Group S (60%. Groups P and G differ significantly than in Group S (p0.05. The prophylactic use of granisetron (40mcg.kg -1 and pethidine(25mg intravenous were found to be effective in preventing postoperative shivering.

Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies

KAUST Repository

Cannistraci, Carlo

2013-02-14

Background: Cryptorchidism is the most frequent congenital disorder in male children; however the genetic causes of cryptorchidism remain poorly investigated. Comparative integratomics combined with systems biology approach was employed to elucidate genetic factors and molecular pathways underlying testis descent. Methods. Literature mining was performed to collect genomic loci associated with cryptorchidism in seven mammalian species. Information regarding the collected candidate genes was stored in MySQL relational database. Genomic view of the loci was presented using Flash GViewer web tool (http://gmod.org/wiki/Flashgviewer/). DAVID Bioinformatics Resources 6.7 was used for pathway enrichment analysis. Cytoscape plug-in PiNGO 1.11 was employed for protein-network-based prediction of novel candidate genes. Relevant protein-protein interactions were confirmed and visualized using the STRING database (version 9.0). Results. The developed cryptorchidism gene atlas includes 217 candidate loci (genes, regions involved in chromosomal mutations, and copy number variations) identified at the genomic, transcriptomic, and proteomic level. Human orthologs of the collected candidate loci were presented using a genomic map viewer. The cryptorchidism gene atlas is freely available online: http://www.integratomics-time.com/cryptorchidism/. Pathway analysis suggested the presence of twelve enriched pathways associated with the list of 179 literature-derived candidate genes. Additionally, a list of 43 network-predicted novel candidate genes was significantly associated with four enriched pathways. Joint pathway analysis of the collected and predicted candidate genes revealed the pivotal importance of the muscle-contraction pathway in cryptorchidism and evidence for genomic associations with cardiomyopathy pathways in RASopathies. Conclusions: The developed gene atlas represents an important resource for the scientific community researching genetics of cryptorchidism. The

BIOADEQUATE APPROACH IS IN PROPHYLACTIC MEDICINE. PROJECT “SMILE OF HEALTH”

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Alexander V. Zakharov

2016-01-01

Full Text Available Importance of forming of thinking of personality is shown as a risk of morbidity factor. Methodology of realization of social initiative is described on development of the new stomatological thinking for doctors-specialists and teachers, and also children and teenagers. The integral going is offered near organization of prophylactic work of doctor, providing success of inlightening with the areas of stomatological knowledge and subsequent forming of stomatological culture and healthy kind of being. Methodology of “residence” of material of employment is offered on the basis of the personal experience, allowing to save interest in a hygiene and prophylaxis with outgrowing of him in the internal necessity of developing personality of child. 

Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?

DEFF Research Database (Denmark)

Murray, Robin M; Quattrone, Diego; Natesan, Sridhar

2016-01-01

over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss...... of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should...

Prophylactic peritoneal dialysis following cardiopulmonary bypass in children is associated with decreased inflammation and improved clinical outcomes.

Science.gov (United States)

Sasser, William C; Dabal, Robert J; Askenazi, David J; Borasino, Santiago; Moellinger, Ashley B; Kirklin, James K; Alten, Jeffrey A

2014-01-01

To investigate impact of prophylactic peritoneal dialysis (PD) on clinical outcomes and inflammatory cytokines in children following cardiac surgery with cardiopulmonary bypass. Prospective before-and-after nonrandomized cohort study. Pediatric cardiovascular intensive care unit in tertiary hospital. Fifty-two consecutive neonates and infants at high risk for postoperative fluid overload following cardiopulmonary bypass. All had PD catheters placed during primary cardiac surgery. Initial 27 patients were managed with passive peritoneal drainage and diuretics (controls). Following 25 patients were started on prophylactic PD in immediate postoperative period and managed per PD protocol (+PD). Cumulative fluid balance, indices of disease severity, and clinical outcomes were prospectively collected. Plasma interleukin-6 and interleukin-8 were measured immediately before-and-after cardiopulmonary bypass and at 24 and 48 hours post-cardiopulmonary bypass. Demographics, diagnoses, and intraoperative variables were similar. Median net fluid balance was more negative in +PD at 24 hours, -24 mL/kg (interquartile range: -62, 11) vs. +18 mL/kg (interquartile range: -26, 11), P = .003, and 48 hours, -88 mL/kg (interquartile range: -132, -54) vs. -46 mL/kg (interquartile range: -84, -12), P = .004. +PD had median 55 mL/kg less fluid intake at 24 hours, P = .058. Peritoneal drain, urine, and chest tube output were comparable over first 24 hours. Mean inotrope score was lower in +PD at 24 hours. +PD had earlier sternal closure--24 hours (interquartile range: 20, 40) vs. 63 hours (interquartile range: 44, 72), P interquartile range: 49, 135) vs. 125 hours (interquartile range: 70, 195), P = .10. +PD experienced lower serum concentrations of interleukin-6 and interleukin-8 at 24 hours. Prophylactic PD is associated with greater net negative fluid balance, decreased inotrope requirements, and lower serum concentrations of inflammatory cytokines in the early postoperative

Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Virus Infection in a Murine Model▿

Science.gov (United States)

Norton, Elizabeth B.; Clements, John D.; Voss, Thomas G.; Cárdenas-Freytag, Lucia

2010-01-01

Prophylactic or therapeutic immunomodulation is an antigen-independent strategy that induces nonspecific immune system activation, thereby enhancing host defense to disease. In this study, we investigated the effect of prophylactic immunomodulation on the outcome of influenza virus infection using three bacterially derived immune-enhancing agents known for promoting distinct immunological profiles. BALB/c mice were treated nasally with either cholera toxin (CT), a mutant form of the CT-related Escherichia coli heat-labile enterotoxin designated LT(R192G), or CpG oligodeoxynucleotide. Mice were subsequently challenged with a lethal dose of influenza A/PR/8/34 virus 24 h after the last immunomodulation treatment and either monitored for survival or sacrificed postchallenge for viral and immunological analysis. Treatment with the three immunomodulators prevented or delayed mortality and weight loss, but only CT and LT(R192G) significantly reduced initial lung viral loads as measured by plaque assay. Analysis performed 4 days postinfection indicated that prophylactic treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers of CD4 T cells, B cells, and dendritic cells and altered costimulatory marker expression in the airways of infected mice, coinciding with reduced expression of pulmonary chemokines and the appearance of inducible bronchus-associated lymphoid tissue-like structures in the lungs. Collectively, these results suggest that, despite different immunomodulatory mechanisms, CT, LT(R192G), and CpG induce an initial inflammatory process and enhance the immune response to primary influenza virus challenge while preventing potentially damaging chemokine expression. These studies provide insight into the immunological parameters and immune modulation strategies that have the potential to enhance the nonspecific host response to influenza virus infection. PMID:20053748

The hippo pathway in heart development, regeneration, and diseases.

Science.gov (United States)

Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang

2015-04-10

The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. © 2015 American Heart Association, Inc.

Fracture prevention by prophylactic femoroplasty of the proximal femur--metallic compared with cemented augmentation.

Science.gov (United States)

Springorum, Hans-Robert; Gebauer, Matthias; Mehrl, Alexander; Stark, Olaf; Craiovan, Benjamin; Püschel, Klaus; Amling, Michael; Grifka, Joachim; Beckmann, Johannes

2014-07-01

To compare 2 different femoral neck augmentation techniques at improving the mechanical strength of the femoral neck. Twenty pairs of human cadaveric femora were randomly divided into 2 groups. In 1 group, the femora were augmented with a steel spiral; the other group with the cemented technique. The untreated contralateral side served as an intraindividual control. Fracture strength was evaluated using an established biomechanical testing scenario mimicking a fall on the greater trochanter (Hayes fall). The peak load to failure was significantly higher in the steel spiral group (P = 0.0024) and in the cemented group (P = 0.001) compared with the intraindividual controls. The peak load to failure showed a median of 3167 N (1825-5230 N) in the spiral group and 2485 N (1066-4395 N) in the spiral control group. The peak load to failure in the cemented group was 3698 N (SD ± 1249 N) compared with 2763 N (SD ± 1335 N) in the cement control group. Furthermore, fracture displacement was clearly reduced in the steel spiral group. Femoral augmentations using steel spirals or cement-based femoroplasty are technically feasible procedures. Our results demonstrate that a prophylactic reinforced proximal femur has higher strength when compared with the untreated contralateral limb. Prophylactic augmentation has potential to become an auxiliary treatment option to protect the osteoporotic proximal femur against fracture.

A randomized, double blind trial of prophylactic fibrinogen to reduce bleeding in cardiac surgery

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Mostafa Sadeghi

2014-07-01

Full Text Available BACKGROUND AND OBJECTIVES: Postoperative bleeding has a great clinical importance and can contribute to increased mortality and morbidity in patients undergoing coronary artery bypass graft surgery. In this prospective, randomized, double-blind study, we evaluated the effect of prophylactic administration of fibrinogen concentrate on post-coronary artery bypass graft surgery bleeding. METHODS: A total of 60 patients undergoing coronary artery bypass surgery were randomly divided into two groups. Patients in the fibrinogen group received 1 g of fibrinogen concentrate 30 min prior to the operation, while patients in the control group received placebo. Post-operative bleeding volumes, prothrombin time, partial thromboplastin time, INR, hemoglobin and transfused blood products in both groups were recorded. A strict red blood cell transfusion protocol was used in all patients. RESULTS: There were no significant differences between intra-operative packed red blood cells infusion in the studied groups (1.0 ± 1.4 in fibrinogen group, and 1.3 ± 1.1 in control group. Less postoperative bleeding was observed in the fibrinogen group (477 ± 143 versus 703 ± 179, p = 0.0001. Fifteen patients in the fibrinogen group and 21 in the control group required post-op packed red blood cells infusion (p = 0.094. No thrombotic event was observed through 72 h after surgery. CONCLUSION: Prophylactic fibrinogen reduces post-operative bleeding in patients undergoing coronary artery bypass graft.

Hedgehog pathway does not play a role in hidradenitis suppurativa pathogenesis

DEFF Research Database (Denmark)

Mozeika, E.; Jemec, G.B.E.; Nürnberg, B.M.

2011-01-01

in normal embryonic skin, hair follicle, sebaceous and sweat gland development. Mutations of hedgehog pathway in adult skin have previously been found in basal cell carcinomas and in alopecia as well as in epidermal cysts and in odontogenic keratocysts. Therefore, we suggested that the hedgehog pathway...

Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory.

Science.gov (United States)

Shen, Fang; Li, Yi-Jing; Shou, Xiao-Jing; Cui, Cai-Lian

2012-09-01

Evidence suggests that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP dependent protein kinase (PKG) signaling pathway plays a key role in memory processing, but the actual participation of this signaling cascade in the hippocampal CA1 during morphine-induced reward memory remains unknown. In this study, we investigated the role of the NO/sGC/PKG signaling pathway in the CA1 on morphine-induced reward memory using a conditioned place preference (CPP) paradigm. We found that rats receiving an intraperitoneal (i.p.) injection of 4mg/kg morphine exhibited CPP, whereas rats treated with only 0.2mg/kg morphine failed to produce CPP. Intra-CA1 injection of the neuronal NO synthase (nNOS) inhibitor 7-NI, the sGC inhibitor ODQ or the PKG inhibitor Rp-8-Br-PET-cGMPS had no effect on the acquisition of CPP by 4mg/kg morphine. Intra-CA1 injection of 7-NI blocked the consolidation of CPP induced by 4mg/kg morphine, and this amnesic effect of 7-NI was mimicked by ODQ and Rp-8-Br-PET-cGMPS. Intra-CA1 injection of the NOS substrate L-arg or the sGC activator YC-1 with an ineffective dose of morphine (0.2mg/kg, i.p.) elicited CPP. This response induced by L-arg or YC-1 was reversed by pre-microinjection of Rp-8-Br-PET-cGMPS in the CA1. These results indicated that the activation of the NO/sGC/PKG signaling pathway in the CA1 is necessary for the consolidation of morphine-related reward memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy

NARCIS (Netherlands)

M.B.M. Tan; E.M.A. Bleiker (Eveline); M.B.E. Menke-Pluymers (Marian); A.R. van Gool (Arthur); S. van Dooren (Silvia); B.N. van Geel (Bert); M.M.A. Tilanus-Linthorst (Madeleine); C.C.M. Bartels (Carina); J.G.M. Klijn (Jan); C.T. Brekelmans (Cecile); C.M. Seynaeve (Caroline)

2009-01-01

textabstractBackground: Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this

A systematic review and meta-analysis of the effect of prophylactic tranexamic acid treatment in major benign uterine surgery

DEFF Research Database (Denmark)

Topsoee, Märta F; Settnes, Annette; Ottesen, Bent

2017-01-01

BACKGROUND: The value of tranexamic acid (TA) treatment as bleeding prophylaxis in major uterine surgery is unclear. OBJECTIVES: To evaluate the antihemorrhagic effect of prophylactic TA treatment in major benign uterine surgery. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, and Web of Science...

White matter pathways in persistent developmental stuttering: Lessons from tractography.

Science.gov (United States)

Kronfeld-Duenias, Vered; Civier, Oren; Amir, Ofer; Ezrati-Vinacour, Ruth; Ben-Shachar, Michal

2018-03-01

Fluent speech production relies on the coordinated processing of multiple brain regions. This highlights the role of neural pathways that connect distinct brain regions in producing fluent speech. Here, we aim to investigate the role of the white matter pathways in persistent developmental stuttering (PDS), where speech fluency is disrupted. We use diffusion weighted imaging and tractography to compare the white matter properties between adults who do and do not stutter. We compare the diffusion properties along 18 major cerebral white matter pathways. We complement the analysis with an overview of the methodology and a roadmap of the pathways implicated in PDS according to the existing literature. We report differences in the microstructural properties of the anterior callosum, the right inferior longitudinal fasciculus and the right cingulum in people who stutter compared with fluent controls. Persistent developmental stuttering is consistently associated with differences in bilateral distributed networks. We review evidence showing that PDS involves differences in bilateral dorsal fronto-temporal and fronto-parietal pathways, in callosal pathways, in several motor pathways and in basal ganglia connections. This entails an important role for long range white matter pathways in this disorder. Using a wide-lens analysis, we demonstrate differences in additional, right hemispheric pathways, which go beyond the replicable findings in the literature. This suggests that the affected circuits may extend beyond the known language and motor pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Current gout treatment and flare in South Korea: Prophylactic duration associated with fewer gout flares.

Science.gov (United States)

Choi, Hyo Jin; Lee, Chan Hee; Lee, Joo Hyun; Yoon, Bo Young; Kim, Hyoun Ah; Suh, Chang Hee; Choi, Sang Tae; Song, Jung Soo; Joo, Ho Yeon; Choi, Sung Jae; Lee, Ji Soo; Shin, Kee Chul; Baek, Han Joo

2017-04-01

To evaluate treatment patterns and clinical factors affecting gout flare in South Korea. We retrospectively examined data from 401 patients seen at nine rheumatology multicenter clinics, under urate lowering therapy (ULT) more than 6 months after stopping prophylactic medication. Demographic data, clinical and laboratory features were collected at the initiation of ULT, upon stopping prophylaxis, and 6 months after. The mean age was 52.2 years and mean disease duration was 25.0 months. The male-to-female count was 387 : 14. The most common ULT starting agent was allopurinol 83.8%. Colchicine (62.3%) was the most commonly prescribed prophylactic agent. During ULT, 134 of the 401 patients (33.4%) experienced at least one gouty attack in the period from stopping prophylaxis to 6 months later. The duration of prophylaxis was different between those with serum uric acid levels below 6 mg/dL and those over 6 mg/dL (P = 0.001). Of the 179 patients (44.6%) who attained target serum uric acid (SUA) levels (6 mg/dL) at the end of prophylaxis, those taking gout flares during ULT. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Efficacy of Prophylactic Mesh in End-Colostomy Construction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Science.gov (United States)

Wang, Shuanhu; Wang, Wenbin; Zhu, Bing; Song, Guolei; Jiang, Congqiao

2016-10-01

Parastomal hernia is a very common complication after colostomy, especially end-colostomy. It is unclear whether prophylactic placement of mesh at the time of stoma formation could prevent parastomal hernia formation after surgery for rectal cancer. A systematic review and meta-analysis were conducted to evaluate the efficacy of prophylactic mesh in end-colostomy construction. PubMed, Embase, and the Cochrane Library were searched, covering records entered from their inception to September 2015. Randomized controlled trials (RCTs) comparing stoma with mesh to stoma without mesh after surgery for rectal cancer were included. The primary outcome was the incidence of parastomal hernia. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were obtained using random effects models. Six RCTs containing 309 patients were included. Parastomal hernia occurred in 24.4 % (38 of 156) of patients with mesh and 50.3 % (77 of 153) of patients without mesh. Meta-analysis showed a lower incidence of parastomal hernia (RR, 0.42; 95 % CI 0.22-0.82) and reoperation related to parastomal hernia (RR, 0.23; 95 % CI 0.06-0.89) in patients with mesh. Stoma-related morbidity was similar between mesh group and non-mesh group (RR, 0.65; 95 % CI 0.33-1.30). Prophylactic placement of a mesh at the time of a stoma formation seems to be associated with a significant reduction in the incidence of parastomal hernia and reoperation related to parastomal hernia after surgery for rectal cancer, but not the rate of stoma-related morbidity. However, the results should be interpreted with caution because of the heterogeneity among the studies.

Supraclavicular failure after breast-conserving therapy in patients with four or more positive axillary lymph nodes when prophylactic supraclavicular irradiation is omitted

International Nuclear Information System (INIS)

Hamamoto, Yasushi; Kataoka, Masaaki; Semba, Takatoshi

2009-01-01

The incidence of supraclavicular metastasis as the initial failure and the failure patterns in patients with four or more positive axillary lymph nodes (PALNs) after breast-conserving therapy (BCT) without prophylactic supraclavicular irradiation were investigated. Between 1991 and 2002, a total of 48 women with four or more PALNs underwent BCT without prophylactic supraclavicular irradiation (33 patients with 4-9 PALNs; 15 patients with ≥10 PALNs). The median follow-up time was 50 months. Among the patients with 4-9 PALNs, 3% had isolated supraclavicular metastasis as the initial failure, and 30% had distant metastasis as the initial failure. Among patients with ≥10 PALNs, 7% had isolated supraclavicular metastasis as the initial failure, and 40% had distant metastasis as the initial failure. The 4-year isolated supraclavicular failure rates were 5% for all patients, 3% for patients with 4-9 PALNs, and 8% for patients with ≥10 PALNs. In patients who had undergone BCT and had had four or more PALNs, the major failure pattern was distant failure with or without locoregional failure; isolated supraclavicular failure as the initial failure comprised a less common failure pattern. Omission of prophylactic supraclavicular irradiation may be acceptable for this subset of patients. (author)

Stochasticity in the yeast mating pathway

International Nuclear Information System (INIS)

Hong-Li, Wang; Zheng-Ping, Fu; Xin-Hang, Xu; Qi, Ouyang

2009-01-01

We report stochastic simulations of the yeast mating signal transduction pathway. The effects of intrinsic and external noise, the influence of cell-to-cell difference in the pathway capacity, and noise propagation in the pathway have been examined. The stochastic temporal behaviour of the pathway is found to be robust to the influence of inherent fluctuations, and intrinsic noise propagates in the pathway in a uniform pattern when the yeasts are treated with pheromones of different stimulus strengths and of varied fluctuations. In agreement with recent experimental findings, extrinsic noise is found to play a more prominent role than intrinsic noise in the variability of proteins. The occurrence frequency for the reactions in the pathway are also examined and a more compact network is obtained by dropping most of the reactions of least occurrence

RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia.

Science.gov (United States)

Edwards, Holly; Xie, Chengzhi; LaFiura, Katherine M; Dombkowski, Alan A; Buck, Steven A; Boerner, Julie L; Taub, Jeffrey W; Matherly, Larry H; Ge, Yubin

2009-09-24

RUNX1 (AML1) encodes the core binding factor alpha subunit of a heterodimeric transcription factor complex which plays critical roles in normal hematopoiesis. Translocations or down-regulation of RUNX1 have been linked to favorable clinical outcomes in acute leukemias, suggesting that RUNX1 may also play critical roles in chemotherapy responses in acute leukemias; however, the molecular mechanisms remain unclear. The median level of RUNX1b transcripts in Down syndrome (DS) children with acute megakaryocytic leukemia (AMkL) were 4.4-fold (P regulation of PIK3CD by RUNX1 was further confirmed by chromatin immunoprecipitation and promoter reporter gene assays. Further, a PI3-kinase inhibitor, LY294002, and cytosine arabinoside synergized in antileukemia effects on Meg-01 and primary pediatric AMkL cells. Our results suggest that RUNX1 may play a critical role in chemotherapy response in AMkL by regulating the PI3-kinase/Akt pathway. Thus, the treatment of AMkL may be improved by integrating PI3-kinase or Akt inhibitors into the chemotherapy of this disease.

The role of the ubiquitination–proteasome pathway in breast cancer: Use of mouse models for analyzing ubiquitination processes

International Nuclear Information System (INIS)

Rossi, Sabrina; Loda, Massimo

2003-01-01

Turnover of several regulatory proteins results from targeted destruction via ubiquitination and subsequent degradation through the proteosome. The timely and irreversible degradation of critical regulators is essential for normal cellular function. The precise biochemical mechanisms that are involved in protein turnover by ubiquitin-mediated degradation have been elucidated using in vitro assays and cell culture systems. However, pathways that lead to ubiquitination of critical regulatory proteins in vivo are more complex, and have both temporal and tissue-specific differences. In vivo models will allow identification of substrates and enzymes of the ubiquitin–proteosome pathway that play important roles in selected tissues and diseases. In addition, assessment of the therapeutic efficacy of drugs designed to inhibit or enhance protein turnover by ubiquitination requires in vivo models. In the present review we describe selected examples of transgenic and knockout models of proteins that are known either to be regulated by ubiquitin-mediated degradation or to have a catalytic function in this process, and to play an important role in breast cancer. We outline the functions of these proteins in vivo and focus on knowledge gained in the comparison of in vivo behavior predicted from cell-free in vitro data or from experiments conducted in cell culture systems

Evolution of mitochondrial cell death pathway: Proapoptotic role of HtrA2/Omi in Drosophila

International Nuclear Information System (INIS)

Igaki, Tatsushi; Suzuki, Yasuyuki; Tokushige, Naoko; Aonuma, Hiroka; Takahashi, Ryosuke; Miura, Masayuki

2007-01-01

Despite the essential role of mitochondria in a variety of mammalian cell death processes, the involvement of mitochondrial pathway in Drosophila cell death has remained unclear. To address this, we cloned and characterized DmHtrA2, a Drosophila homolog of a mitochondrial serine protease HtrA2/Omi. We show that DmHtrA2 normally resides in mitochondria and is up-regulated by UV-irradiation. Upon receipt of apoptotic stimuli, DmHtrA2 is translocated to extramitochondrial compartment; however, unlike its mammalian counterpart, the extramitochondrial DmHtrA2 does not diffuse throughout the cytosol but stays near the mitochondria. RNAi-mediated knock-down of DmHtrA2 in larvae or adult flies results in a resistance to stress stimuli. DmHtrA2 specifically cleaves Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), a cellular caspase inhibitor, and induces cell death both in vitro and in vivo as potent as other fly cell death proteins. Our observations suggest that DmHtrA2 promotes cell death through a cleavage of DIAP1 in the vicinity of mitochondria, which may represent a prototype of mitochondrial cell death pathway in evolution

Contralateral prophylactic mastectomy: current perspectives

Science.gov (United States)

Yao, Katharine; Sisco, Mark; Bedrosian, Isabelle

2016-01-01

There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) in the United States among women diagnosed with unilateral breast cancer, particularly young women. Approximately one-third of women CPM in the US. Most studies have shown that the CPM trend is mainly patient-driven, which reflects a changing environment for newly diagnosed breast cancer patients. The most common reason that women choose CPM is based on misperceptions about CPM’s effect on survival and overestimation of their contralateral breast cancer (CBC) risk. No prospective studies have shown survival benefit to CPM, and the CBC rate for most women is low at 10 years. Fear of recurrence is also a big driver of CPM decisions. Nonetheless, studies have shown that women are mostly satisfied with undergoing CPM, but complications and subsequent surgeries with reconstruction have been associated with dissatisfaction with CPM. Studies on surgeon’s perspectives on CPM are sparse but show that the most common reasons surgeons discuss CPM with patients is because of a suspicious family history or for a patient who is a confirmed BRCA mutation carrier. Studies on the cost–effectiveness of CPM have been conflicting and are highly dependent on patient’s quality of life after CPM. Most recent guidelines for CPM are contradictory. Future areas of research include the development of interventions to better inform patients about CPM, modification of the guidelines to form a more consistent statement, longer term studies on CBC risk and CPM’s effect on survival, and prospective studies that track the psychosocial effects of CPM on body image and sexuality. PMID:27382334

Radioinduced intestinal fibrosis: from molecular mechanisms to therapy applications. Contribution of the TGF--{beta}1, of the CTGF and of the transduction pathway of the Rho/ROCK signal; La fibrose intestinale radio-induite: des mecanismes moleculaires aux applications therapeutiques. Roles du TGF-{beta}1, du CTGF et de la voie de transduction du signal Rho/ROCK

Energy Technology Data Exchange (ETDEWEB)

Haydont, V

2006-12-15

Delayed radiation enteritis is an intestinal fibrosis induced by accidental or therapeutic radiation for pelvic and abdominal cancer treatments. Studies of molecular mechanisms involved in the development and maintenance of fibrosis have showed the respective contribution of CTGF, low TGF-{beta}1 concentrations and Rho/ROCK pathway. Thus, based on the relationship between CTGF, TGF-{beta}1 and Rho pathway, 2 therapeutics strategies have been develop. First, a pravastatin curative gift leads to a fibro-lysis involving an inhibition of Rho and in cascade a reduction of CTGF expression and extracellular matrix deposition. The data suggest that reversal of established radiation fibrosis in the gut is possible. Second, a pravastatin prophylactic gift prevents the installation of a chronic fibrosis but does not protect the tumor. On the base of these results, the radiation therapy department of the Institut Gustave Roussy will soon initiate 2 clinical trials. (author)

Prophylactic role of taurine and its derivatives against diabetes mellitus and its related complications.

Science.gov (United States)

Sarkar, Poulami; Basak, Priyanka; Ghosh, Sumit; Kundu, Mousumi; Sil, Parames C

2017-12-01

Taurine is a conditionally essential amino acid present in the body in free form. Mammalian taurine is synthesized in the pancreas via the cysteine sulfinic acid pathway. Anti-oxidation and anti-inflammation are two main properties through which it exerts its therapeutic effects. Many studies have shown its excellent therapeutic potential against diabetes mellitus and related complications like diabetic neuropathy, retinopathy, nephropathy, hematological dysfunctions, reproductive dysfunctions, liver and pancreas related complications etc. Not only taurine, a number of its derivatives have also been reported to be important in ameliorating diabetic complications. The present review has been aimed to describe the importance of taurine and its derivatives against diabetic metabolic syndrome and related complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer.

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Marshall, Stephen

2006-08-01

Traditionally, nutrients such as glucose and amino acids have been viewed as substrates for the generation of high-energy molecules and as precursors for the biosynthesis of macromolecules. However, it is now apparent that nutrients also function as signaling molecules in functionally diverse signal transduction pathways. Glucose and amino acids trigger signaling cascades that regulate various aspects of fuel and energy metabolism and control the growth, proliferation, and survival of cells. Here, we provide a functional and regulatory overview of three well-established nutrient signaling pathways-the hexosamine signaling pathway, the mTOR (mammalian target of rapamycin) signaling pathway, and the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Nutrient signaling pathways are interconnected, coupled to insulin signaling, and linked to the release of metabolic hormones from adipose tissue. Thus, nutrient signaling pathways do not function in isolation. Rather, they appear to serve as components of a larger "metabolic regulatory network" that controls fuel and energy metabolism (at the cell, tissue, and whole-body levels) and links nutrient availability with cell growth and proliferation. Understanding the diverse roles of nutrients and delineating nutrient signaling pathways should facilitate drug discovery research and the search for novel therapeutic compounds to prevent and treat various human diseases such as diabetes, obesity, and cancer.

Combined Transcriptomic Analysis Revealed AKR1B10 Played an Important Role in Psoriasis through the Dysregulated Lipid Pathway and Overproliferation of Keratinocyte

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Yunlu Gao

2017-01-01

Full Text Available RNA-seq has enabled in-depth analysis of the pathogenesis of psoriasis on the transcriptomic level, and many biomarkers have been discovered to be related to the immune response, lipid metabolism, and keratinocyte proliferation. However, few studies have combined analysis from various datasets. In this study, we integrated different psoriasis RNA-seq datasets to reveal the pathogenesis of psoriasis through the analysis of differentially expressed genes (DEGs, pathway analysis, and functional annotation. The revealed biomarkers were further validated through proliferation phenotypes. The results showed that DEGs were functionally related to lipid metabolism and keratinocyte differentiation dysregulation. The results also showed new biomarkers, such as AKR1B10 and PLA2G gene families, as well as pathways that include the PPAR signaling pathway, cytokine-cytokine receptor interaction, alpha-linoleic acid metabolism, and glycosphingolipid biosynthesis. Using siRNA knockdown assays, we further validated the role that the AKR1B10 gene plays in proliferation. Our study demonstrated not only the dysfunction of the AKR1B10 gene in lipid metabolizing but also its important role in the overproliferation and migration of keratinocyte, which provided evidence for further therapeutic uses for psoriasis.

Role of HIF-1α signaling pathway in osteoarthritis: a systematic review

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Javier Fernández-Torres

Full Text Available Abstract Osteoarthritis (OA is the most common form of arthritis and is frequently diagnosed and managed in primary care; it is characterized by loss of articular hyaline cartilage, which is a unique connective tissue that physiologically lacks blood vessels. Articular cartilage survives in a microenvironment devoid of oxygen, which is regulated by hypoxia inducible factor (HIF-1α. HIF-1α is considered the main transcriptional regulator of cellular and developmental response to hypoxia. To date, the relevance of HIF-1α in the assessment of cartilage has increased since its participation is essential in the homeostasis of this tissue. Taking into account the new emerging insights of HIF-1α in the scientific literature in the last years, we focused the present review on the potential role of HIF-1α signaling pathway in OA development, especially in how some genetic factors may influence the maintenance or breakdown of articular cartilage.

Role of spared pathways in locomotor recovery after body-weight-supported treadmill training in contused rats.

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Singh, Anita; Balasubramanian, Sriram; Murray, Marion; Lemay, Michel; Houle, John

2011-12-01

Body-weight-supported treadmill training (BWSTT)-related locomotor recovery has been shown in spinalized animals. Only a few animal studies have demonstrated locomotor recovery after BWSTT in an incomplete spinal cord injury (SCI) model, such as contusion injury. The contribution of spared descending pathways after BWSTT to behavioral recovery is unclear. Our goal was to evaluate locomotor recovery in contused rats after BWSTT, and to study the role of spared pathways in spinal plasticity after BWSTT. Forty-eight rats received a contusion, a transection, or a contusion followed at 9 weeks by a second transection injury. Half of the animals in the three injury groups were given BWSTT for up to 8 weeks. Kinematics and the Basso-Beattie-Bresnahan (BBB) test assessed behavioral improvements. Changes in Hoffmann-reflex (H-reflex) rate depression property, soleus muscle mass, and sprouting of primary afferent fibers were also evaluated. BWSTT-contused animals showed accelerated locomotor recovery, improved H-reflex properties, reduced muscle atrophy, and decreased sprouting of small caliber afferent fibers. BBB scores were not improved by BWSTT. Untrained contused rats that received a transection exhibited a decrease in kinematic parameters immediately after the transection; in contrast, trained contused rats did not show an immediate decrease in kinematic parameters after transection. This suggests that BWSTT with spared descending pathways leads to neuroplasticity at the lumbar spinal level that is capable of maintaining locomotor activity. Discontinuing training after the transection in the trained contused rats abolished the improved kinematics within 2 weeks and led to a reversal of the improved H-reflex response, increased muscle atrophy, and an increase in primary afferent fiber sprouting. Thus continued training may be required for maintenance of the recovery. Transected animals had no effect of BWSTT, indicating that in the absence of spared pathways this

Antagonism between Hedgehog and Wnt signaling pathways regulates tumorigenicity.

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Ding, Mei; Wang, Xin

2017-12-01

The crosstalk of multiple cellular signaling pathways is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation and metastasis. The Hedgehog (Hh) and Wnt signaling pathways are both considered to be essential regulators of cell proliferation, differentiation and oncogenesis. Recent studies have indicated that the Hh and Wnt signaling pathways are closely associated and involved in regulating embryogenesis and cellular differentiation. Hh signaling acts upstream of the Wnt signaling pathway, and negative regulates Wnt activity via secreted frizzled-related protein 1 (SFRP1), and the Wnt/β-catenin pathway downregulates Hh activity through glioma-associated oncogene homolog 3 transcriptional regulation. This evidence suggests that the imbalance of Hh and Wnt regulation serves a crucial role in cancer-associated processes. The activation of SFRP1, which inhibits Wnt, has been demonstrated to be an important cross-point between the two signaling pathways. The present study reviews the complex interaction between the Hh and Wnt signaling pathways in embryogenesis and tumorigenicity, and the role of SFRP1 as an important mediator associated with the dysregulation of the Hh and Wnt signaling pathways.

A proposed clinical research support career pathway for noninvestigators.

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Smith, Sheree; Gullick, Janice; Ballard, Jacqueline; Perry, Lin

2018-03-08

To discuss the international experience of clinical research support for noninvestigator roles and to propose a new pathway for Australia, to promote a sustainable research support workforce capable of delivering high-quality clinical research. Noninvestigator research support roles are currently characterized by an ad hoc approach to training, with limited role delineation and perceived professional isolation with implications for study completion rates and participant safety. A focused approach to developing and implementing research support pathways has improved patient recruitment, study completion, job satisfaction, and research governance. The Queensland and New South Wales state-based Nurses' Awards, the Australian Qualifications Framework, and a University Professional (Research) Staff Award. Research nurses in the clinical environment improve study coordination, adherence to study protocol, patient safety, and clinical care. A career pathway that guides education and outlines position descriptions and skill sets would enhance development of the research support workforce. This pathway could contribute to changing the patient outcomes through coordination and study completion of high-quality research. A wide consultative approach is required to determine a cost-effective and feasible approach to implementation and evaluation of the proposed pathway. © 2018 John Wiley & Sons Australia, Ltd.

The value of prophylactic vaccinations and antibiotic treatment in post-splenectomy patients: a review

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Lammers AJ

2012-06-01

Full Text Available AJ Jolanda LammersDepartment of Infectious diseases, Tropical Medicine and AIDS, Academic Medical Center, Amsterdam, The NetherlandsAbstract: Although spleen preservation surgery and non-operative management are first-line treatment options, total splenectomy is frequently performed. Splenectomy is performed for a number of indications including idiopathic thrombocytopenic purpura, high-energetic trauma, and hematological malignancy. Following splenectomy, patients are at risk for overwhelming post-splenectomy infection (OPSI, a syndrome that presents with mild symptoms at onset but irreversible multi-organ-failure occurs within hours to days. Since the spleen plays an important role in the immune response to polysaccharide antigens, encapsulated bacteria such as pneumococci are the most frequently described causative organisms of OPSI. Although the incidence of OPSI is low, the associated mortality is reported to be as high as 80%. Because of the overwhelming and frequently irreversible nature of this syndrome, prophylactic measures to prevent OPSI have been recommended. These recommendations include vaccination, use of antibiotics, and continuous patient education. After splenectomy, patients should receive immunizations against the encapsulated bacteria S. pneumoniae, H. influenza, and N. meningitidis. Antibiotic therapy should include prophylaxis as well as “on-demand” antibiotics when infection is suspected. Importantly, patients should receive ongoing education regarding the risks associated with asplenia and precautions to take when infection occurs and when traveling.Keywords: S. pneumoniae, sepsis, splenectomy, vaccination

Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy.

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Cheng, Chi-Hui; Tsai, Ming-Horng; Huang, Yhu-Chering; Su, Lin-Hui; Tsau, Yong-Kwei; Lin, Chi-Jen; Chiu, Cheng-Hsun; Lin, Tzou-Yien

2008-12-01

The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum beta-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum beta-lactamase-producing bacteria or multidrug-resistant uropathogens

Optimizing Prophylactic CPAP in Patients Without Obstructive Sleep Apnoea for High-Risk Abdominal Surgeries: A Meta-regression Analysis.

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Singh, Preet Mohinder; Borle, Anuradha; Shah, Dipal; Sinha, Ashish; Makkar, Jeetinder Kaur; Trikha, Anjan; Goudra, Basavana Gouda

2016-04-01

Prophylactic continuous positive airway pressure (CPAP) can prevent pulmonary adverse events following upper abdominal surgeries. The present meta-regression evaluates and quantifies the effect of degree/duration of (CPAP) on the incidence of postoperative pulmonary events. Medical databases were searched for randomized controlled trials involving adult patients, comparing the outcome in those receiving prophylactic postoperative CPAP versus no CPAP, undergoing high-risk abdominal surgeries. Our meta-analysis evaluated the relationship between the postoperative pulmonary complications and the use of CPAP. Furthermore, meta-regression was used to quantify the effect of cumulative duration and degree of CPAP on the measured outcomes. Seventy-three potentially relevant studies were identified, of which 11 had appropriate data, allowing us to compare a total of 362 and 363 patients in CPAP and control groups, respectively. Qualitatively, Odds ratio for CPAP showed protective effect for pneumonia [0.39 (0.19-0.78)], atelectasis [0.51 (0.32-0.80)] and pulmonary complications [0.37 (0.24-0.56)] with zero heterogeneity. For prevention of pulmonary complications, odds ratio was better for continuous than intermittent CPAP. Meta-regression demonstrated a positive correlation between the degree of CPAP and the incidence of pneumonia with a regression coefficient of +0.61 (95 % CI 0.02-1.21, P = 0.048, τ (2) = 0.078, r (2) = 7.87 %). Overall, adverse effects were similar with or without the use of CPAP. Prophylactic postoperative use of continuous CPAP significantly reduces the incidence of postoperative pneumonia, atelectasis and pulmonary complications in patients undergoing high-risk abdominal surgeries. Quantitatively, increasing the CPAP levels does not necessarily enhance the protective effect against pneumonia. Instead, protective effect diminishes with increasing degree of CPAP.

Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

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Gállego Pérez-Larraya, Jaime; Palma, José Alberto; Carmona-Iragui, María; Fernández-Torrón, Roberto; Irimia, Pablo; Rodríguez-Otero, Paula; Panizo, Carlos; Martínez-Vila, Eduardo

2011-07-01

Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

Pharmacotherapy as prophylactic treatment of post-traumatic stress disorder: a review of the literature.

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Roque, Autumn Pearl

2015-01-01

Post-traumatic stress disorder has a lifetime prevalence of almost 9% in the United States. The diagnosis is associated with increased rates of comorbid substance abuse and increased rates of depression. Providers are taught how to diagnose and treat PTSD, but little discussion is devoted to how to prevent the disorder. Behavioral research in animal studies has provided some evidence for the use of medications in decreasing the fear response and the reconsolidation of memories. A heightened fear response and the re-experience of traumatic memory are key components for diagnosis. The purpose of this literature review is to examine the evidence for pharmacotherapy as prophylactic treatment in acute stress/trauma in order to prevent the development of post-traumatic stress disorder. The body of the review includes discussions on medications, medications as adjunct to script-driven imagery, and special considerations for military, first responders, and women. This article concludes with implications for practice and recommendations for future research. The key words used for the literature search were "prophylactic treatment of PTSD," "pharmacotherapy and trauma," "pharmacological prevention of PTSD," "beta blockers and the prevention of PTSD," "acute stress and prevention of PTSD," "propranolol and PTSD," "secondary prevention of PTSD," and "medications used to prevent PTSD." Findings were categorized by medications and medications as adjunct to script-driven imagery. The literature suggests that hydrocortisone, propranolol, and morphine may decrease symptoms and diagnosis of post-traumatic stress disorder.

The evolution of the TOR pathway and its role in cancer.

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Beauchamp, E M; Platanias, L C

2013-08-22

The target of rapamycin (TOR) pathway is highly conserved among eukaryotes and has evolved to couple nutrient sensing to cellular growth. TOR is found in two distinct signaling complexes in cells, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). These complexes are differentially regulated and act as effectors for the generation of signals that drive diverse cellular processes such as growth, proliferation, protein synthesis, rearrangement of the cytoskeleton, autophagy, metabolism and survival. Mammalian TOR (mTOR) is very important for development in embryos, while in adult organisms it is linked to aging and lifespan effects. In humans, the mTOR pathway is implicated in the tumorigenesis of multiple cancer types and its deregulation is associated with familial cancer syndromes. Because of its high biological relevance, different therapeutic strategies have been developed to target this signaling cascade, resulting in the emergence of unique pharmacological inhibitors that are either already approved for use in clinical oncology or currently under preclinical or clinical development. Multimodal treatment strategies that simultaneously target multiple nodes of the pathway and/or negative feedback regulatory loops may ultimately provide the best therapeutic advantage in targeting this pathway for the treatment of malignancies.

Efficacy of Prophylactic use of Antibiotics to Avoid Flare up During Root Canal Treatment of Nonvital Teeth: A Randomized Clinical Trial

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2015-01-01

Objectives: Flare-up during root canal treatment of non vital teeth is a common clinical incident. The aim of the present study was to assess the effect of prophylactic use of antibiotics to avoid flare up during root canal treatment of the teeth having asymptomatic necrotic pulp. Materials and Methods: A randomized double blind clinical trial with parallel design was conducted on 100 subjects with asymptomatic non vital teeth. They were randomly divided into two groups. The first group (50 participants) was given two gram amoxicillin one hour before the first visit of root canal treatment; the second group (50 participants) did not receive any treatment (control group). In both groups, root canal treatment was performed in two visits. The flare up was assessed by the pain visual analogue scale and based on the swelling criteria. The data were processed and analyzed using SPSS statistical software 17. A p-value of 0.05 or less was considered statistically significant. Results: A total of 80% of participants in the experimental group had flare up while 12% of participants had flare up in the control group. Prophylactic Amoxicillin had no effect on inter-appointment flare up (p > 0.05). There was no relationship between flare up and patient’s age, gender and tooth type (p > 0.05). Conclusion: Prophylactic use of Amoxicillin in asymptomatic non vital teeth before root canal treatment had no effect on the incidence of flare-up. PMID:25954695

Role of the MAPKs/TGF-β1/TRAF6 signaling pathway in postoperative atrial fibrillation.

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Daoliang Zhang

Full Text Available To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD and its role in atrial fibrillation (AF after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis.A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF, respectively. Western blot was also used to measure the protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1. Serum angiotensin II (Ang II levels were assayed using enzyme-linked immunosorbent assay (ELISA.Eighteen patients developed AF, whereas 39 remained in sinus rhythm (SR. The severity of atrial fibrosis was significantly higher in patients who developed AF versus those who remained in SR; the mRNA and protein expression of TGF-β1, TRAF6 and CTGF were significantly higher in patients with AF. The protein expression of phosphorylated MAPKs and TAK1 was significantly increased in patients who developed AF compared with the patients who remained in SR. Serum Ang II levels were significantly higher in patients who developed AF versus those who remained in SR.The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis in patients with RHD, which results in the occurrence of AF after cardiac surgery.

Roles of TGF-β/Smad signaling pathway in pathogenesis and development of gluteal muscle contracture.

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Zhang, Xintao; Ma, Yukun; You, Tian; Tian, Xiaopeng; Zhang, Honglei; Zhu, Qi; Zhang, Wentao

2015-02-01

Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles which is characterized by excessive deposition of collagen in the extracellular matrix. Transforming growth factor (TGF)-βs have been shown to play an important role in the progression of GMC. However, the underlying mechanisms are not entirely clear. We sought to explore the expression of TGF-β/Smad pathway proteins and their downstream targets in gluteal muscle contracture disease. The expression levels of collagens type I/III, TGF-β1, Smad2/3/4/7 and PAI-1 (plasminogen activator inhibitor type 1) in gluteal muscle contraction (GMC) patients were measured using immunohistochemistry, reverse transcription and polymerase chain reaction (RT-PCR) and western blot assays. The expressions of collagens type I/III and TGF-β1 were significantly increased in the contraction band compared with unaffected muscle. In addition, R-Smad phosphorylation and Smad4 protein expression in the contraction band were also elevated, while the expression of Smad7 was significantly decreased in the fibrotic muscle of the GMC patients compared to the unaffected adjacent muscle. The protein and mRNA levels of PAI-1 were also remarkably increased in the contraction band compared with adjacent muscle. Immunohistochemical analysis also demonstrated that the expression levels of TGF-β1 and PAI-1 were higher in contraction band than those in the adjacent muscle. Our data confirm the stimulating effects of the TGF-β/Smad pathway in gluteal muscle contracture disease and reveal the internal changes of TGF-β/Smad pathway proteins and their corresponding targets in gluteal muscle contracture patients.

The Role of MAPK and Dopaminergic Synapse Signaling Pathways in Antidepressant Effect of Electroacupuncture Pretreatment in Chronic Restraint Stress Rats

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Xinjing Yang

2017-01-01

Full Text Available Acupuncture has demonstrated the function in ameliorating depressive-like behaviors via modulating PKA/CREB signaling pathway. To further confirm the antidepressant mechanism of EA on the mitogen-activated protein kinase (MAPK and dopaminergic synapse signaling pathways, 4 target proteins were detected based on our previous iTRAQ analysis. Rats were randomly divided into control group, model group, and electroacupuncture (EA group. Except for the control group, all rats were subjected to 28 days of chronic restraint stress (CRS protocols to induce depression. In the EA group, EA pretreatment at Baihui (GV20 and Yintang (GV29 was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes prior to restraint. The antidepressant-like effect of EA was measured by body weight and open-field test. The protein levels of DAT, Th, Mapt, and Prkc in the hippocampus were examined by using Western blot. The results showed EA could ameliorate the depression-like behaviors and regulate the expression levels of Prkc and Mapt in CRS rats. The effect of EA on DAT and Th expression was minimal. These findings implied that EA pretreatment could alleviate depression through modulating MAPK signaling pathway. The role of EA on dopaminergic synapse signaling pathways needs to be further explored.

Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage

International Nuclear Information System (INIS)

Noda, Taichi; Takahashi, Akihisa; Kondo, Natsuko; Mori, Eiichiro; Okamoto, Noritomo; Nakagawa, Yosuke; Ohnishi, Ken; Zdzienicka, Malgorzata Z.; Thompson, Larry H.; Helleday, Thomas; Asada, Hideo

2011-01-01

The role of the Fanconi anemia (FA) repair pathway for DNA damage induced by formaldehyde was examined in the work described here. The following cell types were used: mouse embryonic fibroblast cell lines FANCA -/- , FANCC -/- , FANCA -/- C -/- , FANCD2 -/- and their parental cells, the Chinese hamster cell lines FANCD1 mutant (mt), FANCGmt, their revertant cells, and the corresponding wild-type (wt) cells. Cell survival rates were determined with colony formation assays after formaldehyde treatment. DNA double strand breaks (DSBs) were detected with an immunocytochemical γH2AX-staining assay. Although the sensitivity of FANCA -/- , FANCC -/- and FANCA -/- C -/- cells to formaldehyde was comparable to that of proficient cells, FANCD1mt, FANCGmt and FANCD2 -/- cells were more sensitive to formaldehyde than the corresponding proficient cells. It was found that homologous recombination (HR) repair was induced by formaldehyde. In addition, γH2AX foci in FANCD1mt cells persisted for longer times than in FANCD1wt cells. These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex. -- Research highlights: → We examined to clarify the repair pathways of formaldehyde-induced DNA damage. Formaldehyde induces DNA double strand breaks (DSBs). → DSBs are repaired through the Fanconi anemia (FA) repair pathway. → This pathway is independent of the FA nuclear core complex. → We also found that homologous recombination repair was induced by formaldehyde.

Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

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Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

2016-01-01

Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716

Tracing Pathways to Higher Education for Refugees: The Role of Virtual Support Networks and Mobile Phones for Women in Refugee Camps

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Dahya, Negin; Dryden-Peterson, Sarah

2017-01-01

In this paper, we explore the role of online social networks in the cultivation of pathways to higher education for refugees, particularly for women. We compare supports garnered in local and offline settings to those accrued through online social networks and examine the differences between women and men. The paper draws on complementary original…

Conservation of PHO pathway in ascomycetes and the role of Pho84

Indian Academy of Sciences (India)

In budding yeast, Saccharomyces cerevisiae, the phosphate signalling and response pathway, known as PHO pathway, monitors phosphate cytoplasmic levels by controlling genes involved in scavenging, uptake and utilization of phosphate. Recent attempts to understand the phosphate starvation response in other ...

Compensatory role of the Nrf2–ARE pathway against paraquat toxicity: Relevance of 26S proteasome activity

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Yasuhiko Izumi

2015-11-01

Full Text Available Oxidative stress and the ubiquitin–proteasome system play a key role in the pathogenesis of Parkinson disease. Although the herbicide paraquat is an environmental factor that is involved in the etiology of Parkinson disease, the role of 26S proteasome in paraquat toxicity remains to be determined. Using PC12 cells overexpressing a fluorescent protein fused to the proteasome degradation signal, we report here that paraquat yielded an inhibitory effect on 26S proteasome activity without an obvious decline in 20S proteasome activity. Relative low concentrations of proteasome inhibitors caused the accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2, which is targeted to the ubiquitin–proteasome system, and activated the antioxidant response element (ARE-dependent transcription. Paraquat also upregulated the protein level of Nrf2 without increased expression of Nrf2 mRNA, and activated the Nrf2–ARE pathway. Consequently, paraquat induced expression of Nrf2-dependent ARE-driven genes, such as γ-glutamylcysteine synthetase, catalase, and hemeoxygenase-1. Knockdown of Nrf2 or inhibition of γ-glutamylcysteine synthetase and catalase exacerbated paraquat-induced toxicity, whereas suppression of hemeoxygenase-1 did not. These data indicate that the compensatory activation of the Nrf2–ARE pathway via inhibition of 26S proteasome serves as part of a cellular defense mechanism to protect against paraquat toxicity.

The role of therapeutic leukapheresis in hyperleukocytotic AML.

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Friederike Pastore

Full Text Available Hyperleukocytosis in AML with leukostasis is a serious life-threatening condition leading to a high early mortality which requires immediate cytoreductive therapy. Therapeutic leukapheresis is currently recommended by the American Society of Apheresis in patients with a WBC>100 G/l with signs of leukostasis, but the role of prophylactic leukapheresis before clinical signs of leukostasis occur is unclear.We retrospectively analyzed the role of leukapheresis in 52 patients (median age 60 years with hyperleukocytotic AML with and without clinical signs of leukostasis. Since leukapheresis was performed more frequently in patients with signs of leukostasis due to the therapeutic policy in our hospital, we developed a risk score for early death within seven days after start of therapy (EDd7 to account for this selection bias and to independently measure the effect of leukapheresis on EDd7.20 patients received leukapheresis in combination to chemotherapy compared to 32 patients who received chemotherapy only. In a multivariate logistic regression model for the estimation of the probability of EDd7 thromboplastin time and creatinine remained as independent significant parameters and were combined to create an EDd7 risk score. The effect of leukapheresis on EDd7 was evaluated in a bivariate logistic regression together with the risk score. Leukapheresis did not significantly change early mortality in all patients with a WBC≥100 G/l.Prophylactic leukapheresis in hyperleukocytotic patients with and without leukostasis did not improve early mortality in our retrospective study. Larger and prospective clinical trials are needed to validate the risk score and to further explore the role of leukapheresis in AML with hyperleukocytosis.

The ERK5 and ERK1/2 signaling pathways play opposing regulatory roles during chondrogenesis of adult human bone marrow-derived multipotent progenitor cells.

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Bobick, Brent E; Matsche, Alexander I; Chen, Faye H; Tuan, Rocky S

2010-07-01

Adult human bone marrow-derived multipotent progenitor cells (MPCs) are able to differentiate into a variety of specialized cell types, including chondrocytes, and are considered a promising candidate cell source for use in cartilage tissue engineering. In this study, we examined the regulation of MPC chondrogenesis by mitogen-activated protein kinases in an attempt to better understand how to generate hyaline cartilage in the laboratory that more closely resembles native tissue. Specifically, we employed the high-density pellet culture model system to assess the roles of ERK5 and ERK1/2 pathway signaling in MPC chondrogenesis. Western blotting revealed that high levels of ERK5 phosphorylation correlate with low levels of MPC chondrogenesis and that as TGF-beta 3-enhanced MPC chondrogenesis proceeds, phospho-ERK5 levels steadily decline. Conversely, levels of phospho-ERK1/2 paralleled the progression of MPC chondrogenesis. siRNA-mediated knockdown of ERK5 pathway components MEK5 and ERK5 resulted in increased MPC pellet mRNA transcript levels of the cartilage-characteristic marker genes SOX9, COL2A1, AGC, L-SOX5, and SOX6, as well as enhanced accumulation of SOX9 protein, collagen type II protein, and Alcian blue-stainable proteoglycan. In contrast, knockdown of ERK1/2 pathway members MEK1 and ERK1 decreased expression of all chondrogenic markers tested. Finally, overexpression of MEK5 and ERK5 also depressed MPC chondrogenesis, as indicated by diminished activity of a co-transfected collagen II promoter-luciferase reporter construct. In conclusion, our results suggest a novel role for the ERK5 pathway as an important negative regulator of adult human MPC chondrogenesis and illustrate that the ERK5 and ERK1/2 kinase cascades play opposing roles regulating MPC cartilage formation. (c) 2010 Wiley-Liss, Inc.

On rational complex of investigation methods in prophylactic examination of patients with chronic kidney diseases

International Nuclear Information System (INIS)

Yazykov, A.S.; Telichko, F.F.

1989-01-01

A retrospective evaluation of the total quantity of X-ray procedures and the radiation degree in 310 patients with chronic kidney diseases is given. It is ascertained that only account of integral absorbed dose in the organ tissues, comprising the doses of X-ray examinations of other organs during the patient lifetime, can serve as the main condition for developing well-grounded recommendations concerning rational complex of examination methods during prophylactic examination of patients with chronic kidney disease. 9 refs.; 4 figs

Physiological Roles of Plant Post-Golgi Transport Pathways in Membrane Trafficking.

Science.gov (United States)

Uemura, Tomohiro

2016-10-01

Membrane trafficking is the fundamental system through which proteins are sorted to their correct destinations in eukaryotic cells. Key regulators of this system include RAB GTPases and soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs). Interestingly, the numbers of RAB GTPases and SNAREs involved in post-Golgi transport pathways in plant cells are larger than those in animal and yeast cells, suggesting that plants have evolved unique and complex post-Golgi transport pathways. The trans-Golgi network (TGN) is an important organelle that acts as a sorting station in the post-Golgi transport pathways of plant cells. The TGN also functions as the early endosome, which is the first compartment to receive endocytosed proteins. Several endocytosed proteins on the plasma membrane (PM) are initially targeted to the TGN/EE, then recycled back to the PM or transported to the vacuole for degradation. The recycling and degradation of the PM localized proteins is essential for the development and environmental responses in plant. The present review describes the post-Golgi transport pathways that show unique physiological functions in plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Severe Neuropsychiatric Reaction in a Deployed Military Member after Prophylactic Mefloquine

Directory of Open Access Journals (Sweden)

Alan L. Peterson

2011-01-01

Full Text Available Recent studies of military personnel who have deployed to Iraq and Afghanistan have reported a number of combat-related psychiatric disorders such as posttraumatic stress disorder, depression, and traumatic brain injury. This case report involves a 27-year-old male active-duty US military service member who developed severe depression, psychotic hallucinations, and neuropsychological sequelae following the prophylactic use of the antimalarial medication mefloquine hydrochloride. The patient had a recent history of depression and was taking antidepressant medications at the time of his deployment to the Middle East. Psychiatrists and other health care providers should be aware of the possible neuropsychiatric side effects of mefloquine in deployed military personnel and should consider the use of other medications for malaria prophylaxis in those individuals who may be at increased risk for side effects.

Recurrence of second trimester miscarriage and extreme preterm delivery at 16 to 27 weeks of gestation with a focus on cervical insufficiency and prophylactic cerclage

DEFF Research Database (Denmark)

Sneider, Kirstine; Christiansen, Ole Bjarne; Sundtoft, Iben Blaabjerg

2016-01-01

INTRODUCTION: The objective of this study was to describe recurrence rates of second trimester miscarriage and extreme preterm delivery by phenotype and use of prophylactic cerclage in a register-based cohort. MATERIAL AND METHODS: We included women with a first second trimester miscarriage......, multiple gestation, uterine anomaly, placental insufficiency, antepartum bleeding, cervical insufficiency, preterm premature rupture of membranes, and intrauterine fetal death. Recurrence rate after a second trimester miscarriage/spontaneous delivery in the period was calculated based on the register data....... In cervical insufficiency outcome was stratified by prophylactic cerclage applied Overall recurrence rate was 7.3% (n = 452), a rate that differed by phenotype from

Mapping Nursing Pathways

Directory of Open Access Journals (Sweden)

Melanie Birks

2015-09-01

Full Text Available Articulated education pathways between the vocational education training sector and universities provide opportunities for students wishing to progress to higher qualifications. Enrolled nurses seeking to advance their career in nursing can choose to enter baccalaureate degree programs through such alternative entry routes. Awarding of credit for prior studies is dependent on accurate assessment of the existing qualification against that which is sought. This study employed a modified Delphi method to inform the development of an evidence-based, structured approach to mapping the pathway from the nationally consistent training package of the Diploma of Nursing to the diversity of baccalaureate nursing programs across Australia. The findings of this study reflect the practical nature of the role of the enrolled nurse, particularly the greater emphasis placed on direct care activities as opposed to those related to professional development and the generation and use of evidence. These findings provide a valuable summative overview of the relationship between the Diploma of Nursing and the expectations of the registered nurse role.

Quantitative analysis of male germline stem cell differentiation reveals a role for the p53-mTORC1 pathway in spermatogonial maintenance.

Science.gov (United States)

Xiong, Mulin; Ferder, Ianina C; Ohguchi, Yasuyo; Wang, Ning

2015-01-01

p53 protects cells from DNA damage by inducing cell-cycle arrest upon encountering genomic stress. Among other pathways, p53 elicits such an effect by inhibiting mammalian target of rapamycin complex 1 (mTORC1), the master regulator of cell proliferation and growth. Although recent studies have indicated roles for both p53 and mTORC1 in stem cell maintenance, it remains unclear whether the p53-mTORC1 pathway is conserved to mediate this process under normal physiological conditions. Spermatogenesis is a classic stem cell-dependent process in which undifferentiated spermatogonia undergo self-renewal and differentiation to maintain the lifelong production of spermatozoa. To better understand this process, we have developed a novel flow cytometry (FACS)-based approach that isolates spermatogonia at consecutive differentiation stages. By using this as a tool, we show that genetic loss of p53 augments mTORC1 activity during early spermatogonial differentiation. Functionally, loss of p53 drives spermatogonia out of the undifferentiated state and causes a consistent expansion of early differentiating spermatogonia until the stage of preleptotene (premeiotic) spermatocyte. The frequency of early meiotic spermatocytes is, however, dramatically decreased. Thus, these data suggest that p53-mTORC1 pathway plays a critical role in maintaining the homeostasis of early spermatogonial differentiation. Moreover, our FACS approach could be a valuable tool in understanding spermatogonial differentiation.

The oxylipin pathway in Arabidopsis.

Science.gov (United States)

Creelman, Robert A; Mulpuri, Rao

2002-01-01

Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays.

The role of microRNA-155/liver X receptor pathway in experimental and idiopathic pulmonary fibrosis.

Science.gov (United States)

Kurowska-Stolarska, Mariola; Hasoo, Manhl K; Welsh, David J; Stewart, Lynn; McIntyre, Donna; Morton, Brian E; Johnstone, Steven; Miller, Ashley M; Asquith, Darren L; Millar, Neal L; Millar, Ann B; Feghali-Bostwick, Carol A; Hirani, Nikhil; Crick, Peter J; Wang, Yuqin; Griffiths, William J; McInnes, Iain B; McSharry, Charles

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF; therefore, microRNAs may reveal novel pathogenic pathways. We sought to determine the regulatory role of microRNA (miR)-155 in the profibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts, and its contribution to experimental pulmonary fibrosis. Bleomycin-induced lung fibrosis in wild-type and miR-155 -/- mice was analyzed by histology, collagen, and profibrotic gene expression. Mechanisms were identified by in silico and molecular approaches and validated in mouse lung fibroblasts and macrophages, and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhibitors. miR-155 -/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGF-β production, and activation of alternatively activated macrophages, contributed by deregulation of the miR-155 target gene the liver X receptor (LXR)α in lung fibroblasts and macrophages. Inhibition of LXRα in experimental lung fibrosis and in IPF lung fibroblasts reduced the exacerbated fibrotic response. Similarly, enforced expression of miR-155 reduced the profibrotic phenotype of IPF and miR-155 -/- fibroblasts. We describe herein a molecular pathway comprising miR-155 and its epigenetic LXRα target that when deregulated enables pathogenic pulmonary fibrosis. Manipulation of the miR-155/LXR pathway may have therapeutic potential for IPF. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

DEFF Research Database (Denmark)

Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

2010-01-01

To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

Policies built upon pathways

NARCIS (Netherlands)

Musterd, S.; Kovács, Z.; Musterd, S.; Kovács, Z.

2013-01-01

After the general introductions, the first substantive part of this volume (Part II) provides concise research-based discussions of policies developed in recognition of the important role played by the pathways along which city-regions have travelled. Our research has shown that it is highly

Targeting Wnt Pathways in Disease

Science.gov (United States)

Zimmerman, Zachary F.; Moon, Randall T.

2012-01-01

Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways. PMID:23001988

Potential role of multiple carbon fixation pathways during lipid accumulation in Phaeodactylum tricornutum

Directory of Open Access Journals (Sweden)

Valenzuela Jacob

2012-06-01

Full Text Available Abstract Background Phaeodactylum tricornutum is a unicellular diatom in the class Bacillariophyceae. The full genome has been sequenced (P. tricornutum gene expression profiles during nutrient-deprivation and lipid-accumulation, cell cultures were grown with a nitrate to phosphate ratio of 20:1 (N:P and whole-genome transcripts were monitored over time via RNA-sequence determination. Results The specific Nile Red (NR fluorescence (NR fluorescence per cell increased over time; however, the increase in NR fluorescence was initiated before external nitrate was completely exhausted. Exogenous phosphate was depleted before nitrate, and these results indicated that the depletion of exogenous phosphate might be an early trigger for lipid accumulation that is magnified upon nitrate depletion. As expected, many of the genes associated with nitrate and phosphate utilization were up-expressed. The diatom-specific cyclins cyc7 and cyc10 were down-expressed during the nutrient-deplete state, and cyclin B1 was up-expressed during lipid-accumulation after growth cessation. While many of the genes associated with the C3 pathway for photosynthetic carbon reduction were not significantly altered, genes involved in a putative C4 pathway for photosynthetic carbon assimilation were up-expressed as the cells depleted nitrate, phosphate, and exogenous dissolved inorganic carbon (DIC levels. P. tricornutum has multiple, putative carbonic anhydrases, but only two were significantly up-expressed (2-fold and 4-fold at the last time point when exogenous DIC levels had increased after the cessation of growth. Alternative pathways that could utilize HCO3- were also suggested by the gene expression profiles (e.g., putative propionyl-CoA and methylmalonyl-CoA decarboxylases. Conclusions The results indicate that P. tricornutum continued carbon dioxide reduction when population growth was arrested and different carbon-concentrating mechanisms were used dependent upon exogenous

Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage

Energy Technology Data Exchange (ETDEWEB)

Noda, Taichi [Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Kondo, Natsuko [Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan); Mori, Eiichiro [Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Ken [Department of Biology, Ibaraki Prefectual University of Health Sciences, 4669-2 Ami, Ami-mati, Inasiki-gun, Ibaraki 300-0394 (Japan); Zdzienicka, Malgorzata Z. [Department of Molecular Cell Genetics, Collegium Medicum in Bydgoszcz, Nicolaus-Copernicus-University in Torun, ul. Sklodowskiej-Curie 9, 85-094 Bydgoszcz (Poland); Thompson, Larry H. [Biosciences and Biotechnology Division, L452, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551-0808 (United States); Helleday, Thomas [Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ (United Kingdom); Department of Genetics, Microbiology and Toxicology Stockholm University, SE-106 91 Stockholm (Sweden); Asada, Hideo [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); and others

2011-01-07

The role of the Fanconi anemia (FA) repair pathway for DNA damage induced by formaldehyde was examined in the work described here. The following cell types were used: mouse embryonic fibroblast cell lines FANCA{sup -/-}, FANCC{sup -/-}, FANCA{sup -/-}C{sup -/-}, FANCD2{sup -/-} and their parental cells, the Chinese hamster cell lines FANCD1 mutant (mt), FANCGmt, their revertant cells, and the corresponding wild-type (wt) cells. Cell survival rates were determined with colony formation assays after formaldehyde treatment. DNA double strand breaks (DSBs) were detected with an immunocytochemical {gamma}H2AX-staining assay. Although the sensitivity of FANCA{sup -/-}, FANCC{sup -/-} and FANCA{sup -/-}C{sup -/-} cells to formaldehyde was comparable to that of proficient cells, FANCD1mt, FANCGmt and FANCD2{sup -/-} cells were more sensitive to formaldehyde than the corresponding proficient cells. It was found that homologous recombination (HR) repair was induced by formaldehyde. In addition, {gamma}H2AX foci in FANCD1mt cells persisted for longer times than in FANCD1wt cells. These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex. -- Research highlights: {yields} We examined to clarify the repair pathways of formaldehyde-induced DNA damage. Formaldehyde induces DNA double strand breaks (DSBs). {yields} DSBs are repaired through the Fanconi anemia (FA) repair pathway. {yields} This pathway is independent of the FA nuclear core complex. {yields} We also found that homologous recombination repair was induced by formaldehyde.

Does prophylactic administration of systemic antibiotics prevent postoperative inflammatory complications after third molar surgery?

Science.gov (United States)

Halpern, Leslie R; Dodson, Thomas B

2007-02-01

To estimate and compare the frequencies of inflammatory complications after third molar (M3) surgery in subjects receiving intravenous prophylactic antibiotics or saline placebo. Using a placebo-controlled, double-blind, randomized clinical trial, the investigators enrolled a sample composed of subjects who required extraction of at least 1 impacted M3 and requested intravenous sedation or general anesthesia. The predictor variable was treatment group classified as active treatment (penicillin or clindamycin for penicillin-allergic subjects) or placebo (0.9% saline). Study medications were randomly assigned. Both surgeon and subject were blinded to treatment assignment. The medication was administered intravenously prior to any incision. The outcome variable was postoperative inflammatory complication classified as present or absent and included alveolar osteitis (AO) or surgical site infection (SSI). Other variables were demographic, anatomic, or operative. Descriptive and bivariate statistics were computed. Statistical significance was set at P < or = .05, single-tailed test of hypothesis. The sample was composed of 118 subjects (n = 59 per study group). In the active treatment group, there were no postoperative inflammatory complications. In the placebo group, 5 subjects (8.5%) were diagnosed with SSI, (P = .03). No subject met the case definition for AO. All SSIs were associated with the removal of partial bony or full bony impacted mandibular M3s. In the setting of third molar removal, these results suggest that the use of intravenous antibiotics administered prophylactically decrease the frequency of SSIs. The authors cannot comment on the efficacy of intravenous antibiotics in comparison to other antibacterial treatment regimens, eg chlorhexidine mouthrinse or intrasocket antibiotics.

The researchers' role in knowledge translation: a realist evaluation of the development and implementation of diagnostic pathways for cancer in two United Kingdom localities.

Science.gov (United States)

Banks, Jon; Wye, Lesley; Hall, Nicola; Rooney, James; Walter, Fiona M; Hamilton, Willie; Gjini, Ardiana; Rubin, Greg

2017-12-13

In examining an initiative to develop and implement new cancer diagnostic pathways in two English localities, this paper evaluates 'what works' and examines the role of researchers in facilitating knowledge translation amongst teams of local clinicians and policy-makers. Using realist evaluation with a mixed methods case study approach, we conducted documentary analysis of meeting minutes and pathway iterations to map pathway development. We interviewed 14 participants to identify the contexts, mechanisms and outcomes (CMOs) that led to successful pathway development and implementation. Interviews were analysed thematically and four CMO configurations were developed. One site produced three fully implemented pathways, while the other produced two that were partly implemented. In explaining the differences, we found that a respected, independent, well-connected leader modelling partnership working and who facilitates a local, stable group that agree about the legitimacy of the data and project (context) can empower local teams to become sufficiently autonomous (mechanism) to develop and implement research-based pathways (outcome). Although both teams designed relevant, research-based cancer pathways, in the site where the pathways were successfully implemented the research team merely assisted, while, in the other, the research team drove the initiative. Based on our study findings, local stakeholders can apply local and research knowledge to develop and implement research-based pathways. However, success will depend on how academics empower local teams to create autonomy. Crucially, after re-packaging and translating research for local circumstances, identifying fertile environments with the right elements for implementation and developing collaborative relationships with local leaders, academics must step back.

Molecular Pathways

Science.gov (United States)

Lok, Benjamin H.; Powell, Simon N.

2012-01-01

The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

A prospective, randomised trial of prophylactic antibiotics versus bag extraction in the prophylaxis of wound infection in laparoscopic cholecystectomy.

Science.gov (United States)

Harling, R; Moorjani, N; Perry, C; MacGowan, A P; Thompson, M H

2000-11-01

Septic complications are rare following laparoscopic cholecystectomy if prophylactic antibiotics are given, as demonstrated in previous studies. Antibiotic treatment may be unnecessary and, therefore, undesirable, so we compared two forms of prophylaxis: a cephalosporin antibiotic and bag extraction of the dissected gallbladder. A total of 76 patients undergoing laparoscopic cholecystectomy were randomised to either receive an antibiotic or to have their gallbladder removed from the abdomen in a plastic bag. Complicated cases were excluded. There was a total of 6 wound infections (7.9%), 3 in each of the study groups. All these were associated with skin commensals. There were no other septic complications. Bacteriological studies grouped the organisms isolated from the bile and the wound as potential pathogens and likely commensals. A total of 10 potential pathogens were isolated, 9 of which were found in the group receiving antibiotics. We conclude that septic sequelae of uncomplicated laparoscopic cholecystectomy are uncommon, but clearly not entirely prevented by antibiotic or mechanical prophylaxis. Prophylactic antibiotics may not be required in uncomplicated laparoscopic cholecystectomy. Further study is warranted.

A comparison of traditional vs. Canadian tailored prophylaxis dosing of prophylactic factor infusions in children with haemophilia A and B in a single hemophilia treatment center.

Science.gov (United States)

Dodd, C; Watts, R G

2012-07-01

Prophylactic infusion of clotting factor concentrates is a developing standard of care for individuals with haemophilia. The ideal schedule and techniques of prophylactic infusions remain incompletely defined. Our aim was to determine the optimal techniques and schedules for factor prophylaxis in paediatric patients. A retrospective electronic medical record review of all children treated with prophylactic factor infusions in a single Haemophilia Treatment Center was conducted. Comparison of traditional vs. Canadian dosing regimens and primary vs. secondary prophylaxis was made. Failure of prophylaxis was defined as the first serious bleed. A total of 58 children were identified for review. Five cases were excluded (four due to high titre inhibitors and one due to repeated non-compliance), thus there were 53 total cases: 46 with severe haemophilia, 2 with moderate haemophilia, 5 with mild haemophilia, 44 with haemophilia A and 9 with haemophilia B; 32 Traditional dosing and 21 Canadian dosing regimens. Patients on primary prophylaxis had a decreased failure rate (25%) compared to children treated with secondary prophylaxis (67%) regardless of technique of prophylaxis. When compared to a 'Traditional' factor prophylaxis schedule, the 'Canadian' tailored prophylaxis protocol was comparable with the exception of a decreased use of implanted venous devices in the 'Canadian' group. Ongoing bleeding (primarily joint bleeds) occurs with all prophylactic regimens. The lowest incidence of treatment failure was noted in children who began primary prophylaxis at a young age and before initial joint bleeds. Primary prophylaxis is superior to secondary prophylaxis regardless of dosing regimen. Traditional and Canadian dosing regimens were equivalent in outcome when measured over several years of follow-up. © 2012 Blackwell Publishing Ltd.

Prophylactic Effect of Probiotics on the Development of Experimental Autoimmune Myasthenia Gravis

Science.gov (United States)

Chae, Chang-Suk; Kwon, Ho-Keun; Hwang, Ji-Sun; Kim, Jung-Eun; Im, Sin-Hyeog

2012-01-01

Probiotics are live bacteria that confer health benefits to the host physiology. Although protective role of probiotics have been reported in diverse diseases, no information is available whether probiotics can modulate neuromuscular immune disorders. We have recently demonstrated that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental disorders in mice model. In this study we further investigated whether IRT5 probiotics could modulate the progression of experimental autoimmune myasthenia gravis (EAMG). Myasthenia gravis (MG) is a T cell dependent antibody mediated autoimmune disorder in which acetylcholine receptor (AChR) at the neuromuscular junction is the major auto-antigen. Oral administration of IRT5 probiotics significantly reduced clinical symptoms of EAMG such as weight loss, body trembling and grip strength. Prophylactic effect of IRT5 probiotics on EMAG is mediated by down-regulation of effector function of AChR-reactive T cells and B cells. Administration of IRT5 probiotics decreased AChR-reactive lymphocyte proliferation, anti-AChR reactive IgG levels and inflammatory cytokine levels such as IFN-γ, TNF-α, IL-6 and IL-17. Down-regulation of inflammatory mediators in AChR-reactive lymphocytes by IRT5 probiotics is mediated by the generation of regulatory dendritic cells (rDCs) that express increased levels of IL-10, TGF-β, arginase 1 and aldh1a2. Furthermore, DCs isolated from IRT5 probiotics-fed group effectively converted CD4+ T cells into CD4+Foxp3+ regulatory T cells compared with control DCs. Our data suggest that IRT5 probiotics could be applicable to modulate antibody mediated autoimmune diseases including myasthenia gravis. PMID:23284891

A potential role of substrate as a base for deprotonation pathway in Rh-catalysed C-H amination of heteroArenes: DFT insights

KAUST Repository

Ajitha, Manjaly John

2016-03-29

The possibility of direct introduction of a new functionality through C–H bond activation is an attractive strategy in covalent synthesis. Here, we investigated the mechanism of Rh-catalysed C-H amination of the hetero-aryl substrate (2-phenylpyridine) using phenyl azide as nitrogen source by density functional theory (DFT). For the deprotocyclometallation and protodecyclometallation processes of the title reaction, we propose a stepwise base-assisted mechanism (pathway I) instead of previously reported concerted mechanism (pathway II). In the new mechanism proposed here, 2-phenylpyridine acts as a base in the initial deprotonation step (C-H bond cleavage) and transports the proton towards the final protonation step. In fact, the N-H bond of the strong conjugate acid (formed during initial C-H bond cleavage) considered in pathway I (via TS4) is more acidic than the C-H bond of the neutral substrate considered in pathway II (via TS5). The higher activation barrier of TS5 mainly originates from the ring strain of the four membered cyclic transition state. The vital role of base, as disclosed here, can potentially have broader mechanistic implications for the development of reaction conditions of transition metal catalysed reactions.

Prophylactic cefazolin in amnioinfusions administered for meconium-stained amniotic fluid.

Science.gov (United States)

Edwards, R K; Duff, P

1999-01-01

OBJECTIVE: To determine if amnioinfusion with an antibiotic solution decreased the rate of clinical chorioamnionitis and puerperal endometritis in patients with meconium-stained amniotic fluid. METHODS: Patients in labor at 36 weeks of gestation or greater with singleton pregnancies and meconium-stained amniotic fluid were randomized to receive either cefazolin, 1 g/1,000 mL, of normal saline (n = 90) or normal saline (n = 93) amnioinfusion. Rates of clinically diagnosed chorioamnionitis and endometritis and of suspected and culture-proven neonatal infection were determined. RESULTS: Between the study and control groups, the incidences of clinical chorioamnionitis (7.8% vs. 8.6%), endometritis (2.4% vs. 3.5%), aggregate intrauterine infection (10.0% vs. 11.8%), suspected neonatal infection (17.8% vs. 21.5%), and proven neonatal infection (0.0% vs. 2.2%) were not significantly different. CONCLUSIONS: Prophylactic use of cefazolin in amnioinfusions did not significantly reduce rates of maternal or neonatal infection in patients with meconium-stained amniotic fluid. PMID:10371474

Prophylactic cranial irradiation in patients with small cell lung cancer

DEFF Research Database (Denmark)

Ramlov, Anne; Tietze, Anna; Khalil, Azza Ahmed

2012-01-01

BACKGROUND: Prophylactic cerebral irradiation (PCI) is a standard treatment for all small cell lung cancer (SCLC) patients with response to chemotherapy. The aims of this study were: to evaluate patients undergoing PCI with regard to cerebral recurrence rate, site of recurrence, and overall...... retrospectively with regard to disease stage, treatment, date of PCI, steroid dose during PCI, toxicity, time to recurrence, site of recurrence and time of death. The median follow up time was 16.6months (range 3-54months). RESULTS: Of the 118 patients undergoing PCI, 74 had limited disease (LD-SCLC) and 44 had...... extensive disease (ED-SCLC). The median age was 65years (range 46-80years). The median overall survival of all patients from the time of diagnosis was 16.0months (CI 95% 13.0-19.0), in LD-SCLC it was 24.0months (CI 95% 19.6-28.3), and in ED-SCLC it was 12.0months (CI 95% 9.6-14.4). Twenty-one patients (17...

Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

Directory of Open Access Journals (Sweden)

Sudipta Tripathi

2015-02-01

Full Text Available Tolerance of the fetus by the maternal immune system is regulated through various mechanisms involving the different immune cells, both in the periphery and locally at the feto-maternal interface. The maternal T lymphocytes are aware of the paternal fetal antigens and a state of dynamic T cell homeostasis is maintained in the uterus during gestation, which involves increase in antigen-specific regulatory T cell (Treg proliferation, increase in apoptosis of antigen-specific effector T cells, and inhibition of excessive inflammation post successful implantation to ensure tolerance to the fetus. The Tregs play an important role in the maintenance of tolerance during gestation. Recently, the inflammatory T helper type 17 (Th17 cells are reported to have a role in loss of tolerance to the fetus. The interaction between costimulatory molecule programmed death 1 (PD1 and its ligand PDL1 is known to play a role in regulating both the Tregs and Th17 cells. Here we discuss how the PD1/PDL1 pathway affects these two T cell populations and its role in feto-maternal tolerance.

Salicylic acid-independent plant defence pathways

OpenAIRE

Pieterse, C.M.J.; Loon, L.C. van

1999-01-01

Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are independent of salicylic acid. Evidence is emerging that jasmonic acid and ethylene play key roles in these salicylic acid-independent pathways. Cross-talk between the salicylic acid-dependent and the salicy...

Functions of the Drosophila JAK-STAT pathway

Science.gov (United States)

Amoyel, Marc; Bach, Erika A.

2012-01-01

JAK-STAT signaling has been proposed to act in numerous stem cells in a variety of organisms. Here we provide an overview of its roles in three well characterized stem cell populations in Drosophila, in the intestine, lymph gland and testis. In flies, there is a single JAK and a single STAT, which has made the genetic dissection of pathway function considerably easier and facilitated the analysis of communication between stem cells, their niches and offspring. Studies in flies have revealed roles for this pathway as diverse as regulating bona fide intrinsic self-renewal, integrating response to environmental cues that control quiescence and promoting mitogenic responses to stress. PMID:24058767

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Directory of Open Access Journals (Sweden)

Maulilio John Kipanyula

2016-01-01

Full Text Available The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA and regulator of calcineurin 1 (RCAN1 also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

The Hippo Pathway: Immunity and Cancer.

Science.gov (United States)

Taha, Zaid; J Janse van Rensburg, Helena; Yang, Xiaolong

2018-03-28

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

Stimulation of the Salicylic Acid Pathway Aboveground Recruits Entomopathogenic Nematodes Belowground.

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Camila Cramer Filgueiras

Full Text Available Plant defense pathways play a critical role in mediating tritrophic interactions between plants, herbivores, and natural enemies. While the impact of plant defense pathway stimulation on natural enemies has been extensively explored aboveground, belowground ramifications of plant defense pathway stimulation are equally important in regulating subterranean pests and still require more attention. Here we investigate the effect of aboveground stimulation of the salicylic acid pathway through foliar application of the elicitor methyl salicylate on belowground recruitment of the entomopathogenic nematode, Steinernema diaprepesi. Also, we implicate a specific root-derived volatile that attracts S. diaprepesi belowground following aboveground plant stimulation by an elicitor. In four-choice olfactometer assays, citrus plants treated with foliar applications of methyl salicylate recruited S. diaprepesi in the absence of weevil feeding as compared with negative controls. Additionally, analysis of root volatile profiles of citrus plants receiving foliar application of methyl salicylate revealed production of d-limonene, which was absent in negative controls. The entomopathogenic nematode S. diaprepesi was recruited to d-limonene in two-choice olfactometer trials. These results reinforce the critical role of plant defense pathways in mediating tritrophic interactions, suggest a broad role for plant defense pathway signaling belowground, and hint at sophisticated plant responses to pest complexes.

Stimulation of the Salicylic Acid Pathway Aboveground Recruits Entomopathogenic Nematodes Belowground

Science.gov (United States)

Filgueiras, Camila Cramer; Willett, Denis S.; Junior, Alcides Moino; Pareja, Martin; Borai, Fahiem El; Dickson, Donald W.; Stelinski, Lukasz L.; Duncan, Larry W.

2016-01-01

Plant defense pathways play a critical role in mediating tritrophic interactions between plants, herbivores, and natural enemies. While the impact of plant defense pathway stimulation on natural enemies has been extensively explored aboveground, belowground ramifications of plant defense pathway stimulation are equally important in regulating subterranean pests and still require more attention. Here we investigate the effect of aboveground stimulation of the salicylic acid pathway through foliar application of the elicitor methyl salicylate on belowground recruitment of the entomopathogenic nematode, Steinernema diaprepesi. Also, we implicate a specific root-derived volatile that attracts S. diaprepesi belowground following aboveground plant stimulation by an elicitor. In four-choice olfactometer assays, citrus plants treated with foliar applications of methyl salicylate recruited S. diaprepesi in the absence of weevil feeding as compared with negative controls. Additionally, analysis of root volatile profiles of citrus plants receiving foliar application of methyl salicylate revealed production of d-limonene, which was absent in negative controls. The entomopathogenic nematode S. diaprepesi was recruited to d-limonene in two-choice olfactometer trials. These results reinforce the critical role of plant defense pathways in mediating tritrophic interactions, suggest a broad role for plant defense pathway signaling belowground, and hint at sophisticated plant responses to pest complexes. PMID:27136916

The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity

Energy Technology Data Exchange (ETDEWEB)

Yin, Li [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Dai, Yanlin [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Medical Laboratory Technology Department, Chuxiong Medical College, Yunnan 675005 (China); Cui, Zhihong; Jiang, Xiao; Liu, Wenbin; Han, Fei; Lin, Ao; Cao, Jia [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Liu, Jinyi, E-mail: jinyiliutmmu@163.com [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China)

2017-01-01

Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate. The testes from BPA-treated mice showed fewer spermatogenic cells and sperm in the seminiferous tubules. In addition, BPA caused reactive oxygen species (ROS) accumulation. Previous study has verified that mitochondrion was the organelle affected by the BPA-triggered ROS accumulation. We found that BPA induced damage to the endoplasmic reticulum (ER) in addition to mitochondria, and most ER stress-related proteins were activated in cellular and animal models. Knocking down of the PERK/EIF2α/chop pathway, one of the ER stress pathways, partially recovered the BPA-induced cell apoptosis. In addition, an ROS scavenger attenuated the expression of the PERK/EIF2α/chop pathway-related proteins. Taken together, these data suggested that the ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced male reproductive toxicity. - Highlights: • BPA exposure caused the damage of the endoplasmic reticulum. • BPA exposure activated ER stress related proteins in male reproductive system. • ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced toxicity.

Effect of prophylactic polishing protocols on the surface roughness of esthetic restorative materials.

Science.gov (United States)

Neme, A L; Frazier, K B; Roeder, L B; Debner, T L

2002-01-01

Many polishing protocols have been evaluated in vitro for their effect on the surface roughness of restorative materials. These results have been useful in establishing protocols for in vivo application. However, limited research has focused on the subsequent care and maintenance of esthetic restorations following their placement. This investigation evaluated the effect of five polishing protocols that could be implemented at recall on the surface roughness of five direct esthetic restorative materials. Specimens (n=25) measuring 8 mm diameter x 3 mm thick were fabricated in an acrylic mold using five light-cured resin-based materials (hybrid composite, microfilled composite, packable composite, compomer and resin-modified glass ionomer). After photopolymerization, all specimens were polished with Sof-Lex Disks to produce an initial (baseline) surface finish. All specimens were then polished with one of five prophylactic protocols (Butler medium paste, Butler coarse paste, OneGloss, SuperBuff or OneGloss & SuperBuff). The average surface roughness of each treated specimen was determined from three measurements with a profilometer (Surface 1). Next, all specimens were brushed 60,000 times at 1.5 Hz using a brush-head force of 2 N on a Manly V-8 cross-brushing machine in a 50:50 (w/w) slurry of toothpaste and water. The surface roughness of each specimen was measured after brushing (Surface 2) followed by re-polishing with one of five protocols, then final surface roughness values were determined (Surface 3). The data were analyzed using repeated measures ANOVA. Significant differences (p=0.05) in surface roughness were observed among restorative materials and polishing protocols. The microfilled and hybrid resin composite yielded significantly rougher surfaces than the other three materials following tooth brushing. Prophylactic polishing protocols can be used to restore a smooth surface on resin-based esthetic restorative materials following simulated tooth

A pivotal role of the jasmonic acid signal pathway in mediating radiation-induced bystander effects in Arabidopsis thaliana.

Science.gov (United States)

Wang, Ting; Xu, Wei; Deng, Chenguang; Xu, Shaoxin; Li, Fanghua; Wu, Yuejin; Wu, Lijun; Bian, Po

Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have been well demonstrated in vivo, little is known about their underlying mechanisms, particularly with regard to the participating signaling molecules and signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive derivatives are well accepted as systemic signal transducers that are produced in response to various environmental stresses. It is therefore speculated that the JA signal pathway might play a potential role in mediating radiation-induced bystander signaling of root-to-shoot. In the present study, pretreatment of seedlings with Salicylhydroxamic acid, an inhibitor of lipoxigenase (LOX) in JA biosynthesis, significantly suppressed RIBE-mediated expression of the AtRAD54 gene. After root irradiation, the aerial parts of A. thaliana mutants deficient in JA biosynthesis (aos) and signaling cascades (jar1-1) showed suppressed induction of the AtRAD54 and AtRAD51 genes and TSI and 180-bp repeats, which have been extensively used as endpoints of bystander genetic and epigenetic effects in plants. These results suggest an involvement of the JA signal pathway in the RIBE of plants. Using the root micro-grafting technique, the JA signal pathway was shown to participate in both the generation of bystander signals in irradiated root cells and radiation responses in the bystander aerial parts of plants. The over-accumulation of endogenous JA in mutant fatty acid oxygenation up-regulated 2 (fou2), in which mutation of the Two Pore Channel 1 (TPC1) gene up-regulates expression of the LOX and allene oxide synthase (AOS) genes, inhibited RIBE-mediated expression of the AtRAD54 gene, but up-regulated expression of the AtKU70 and AtLIG4 genes in the non-homologous end joining (NHEJ) pathway. Considering that NHEJ is employed by plants with increased DNA damage, the switch from HR to NHEJ suggests that over-accumulation of endogenous JA might enhance the radiosensitivity of plants

Naratriptan in the Prophylactic Treatment of Cluster Headache.

Science.gov (United States)

Ito, Yasuo; Mitsufuji, Takashi; Asano, Yoshio; Shimazu, Tomokazu; Kato, Yuji; Tanahashi, Norio; Maruki, Yuichi; Sakai, Fumihiko; Yamamoto, Toshimasa; Araki, Nobuo

2017-10-01

Objective Naratriptan has been reported to reduce the frequency of cluster headache. The purpose of this study was to determine whether naratriptan is effective as a prophylactic treatment for cluster headache in Japan. Methods We retrospectively reviewed all 43 patients with cluster headache who received preventive treatment with naratriptan from April 2009 to April 2015. The International Classification of Headache Disorders, 3rd Edition (beta version) (ICHD-3 beta) was used to diagnose cluster headache. This study was conducted at 3 centers (Department of Neurology, Saitama Medical University; Saitama Neuropsychiatric Institute; Saitama Medical University International Medical Center). Patients were recruited from these specialized headache outpatient centers. Naratriptan was taken before the patient went to bed. Results The study population included 30 men (69.8%) and 13 women (30.2%). Twenty-two cases received other preventive treatments (51.2%), while 21 cases only received naratriptan (48.8%). Among the 43 cases, 37 patients (86.0%) achieved an improvement of cluster headache on naratriptan. Conclusion Naratriptan has been suggested as a preventive medicine for cluster headache because of the longer the biological half-life in comparison to other triptans. The internal use of naratriptan 2 hours before attacks appears to achieve a good response in patients with cluster headache.

Prophylactic Appendectomy during Laparoscopic Surgery for Other Conditions

Directory of Open Access Journals (Sweden)

S. Occhionorelli

2014-01-01

Full Text Available Acute appendicitis remains the most common surgical emergency. Laparoscopy has gained increasing favor as a method of both investigating right iliac fossa pain and treating the finding of appendicitis. A question arises: what to do with an apparent healthy appendix discovered during laparoscopic surgery for other pathology. We present a case of unilateral hydroureteronephrosis complicated with rupture of the renal pelvis, due to gangrenous appendicitis with abscess of the right iliopsoas muscle and periappendicular inflammation in a 67-year-old woman, who underwent laparoscopic right annessiectomy for right ovarian cyst few years earlier, in which a healthy appendix was left inside. There is a lack of consensus in the literature about what to do with a normal appendix. The main argument for removing an apparently normal appendix is that endoluminal appendicitis may not be recognized during surgery, leading to concern that an abnormal appendix is left in place. Because of a lack of evidence from randomized trials, it remains unclear whether the benefits of routine elective coincidental appendectomy outweigh the costs and risks of morbidity associated with this prophylactic procedure. Nevertheless, it appears, from limited data, that women aged 35 years and under benefit most from elective coincidental appendectomy.

Minimal metabolic pathway structure is consistent with associated biomolecular interactions

DEFF Research Database (Denmark)

Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E.

2014-01-01

Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we......, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated....

RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway.

Science.gov (United States)

Keuling, Angela M; Felton, Kathleen E A; Parker, Arabesque A M; Akbari, Majid; Andrew, Susan E; Tron, Victor A

2009-08-17

Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity.

Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin

DEFF Research Database (Denmark)

Pilely, Katrine; Rosbjerg, Anne; Genster, Ninette

2016-01-01

Cholesterol crystals (CC) play an essential role in the formation of atherosclerotic plaques. CC activate the classical and the alternative complement pathways, but the role of the lectin pathway is unknown. We hypothesized that the pattern recognition molecules (PRMs) from the lectin pathway bind...... CC and function as an upstream innate inflammatory signal in the pathophysiology of atherosclerosis. We investigated the binding of the PRMs mannose-binding lectin (MBL), ficolin-1, ficolin-2, and ficolin-3, the associated serine proteases, and complement activation products to CC in vitro using...... recognize CC and provides evidence for an important role for this pathway in the inflammatory response induced by CC in the pathophysiology of atherosclerosis....

Emergence of trimethoprim-resistant Escherichia coli in healthy persons in the absence of prophylactic or therapeutic antibiotics during travel to Guadalajara, Mexico.

Science.gov (United States)

Huang, D B; Jiang, Z D; Ericsson, C D; Adachi, J; Dupont, H L

2001-01-01

Thirty-nine healthy US students without diarrheal disease and who had not received prophylactic or therapeutic antibiotics were monitored for emergence of trimethoprim-resistant gram-negative fecal flora for a 3-week period after arrival in Guadalajara, Mexico. During this time period, most students showed no change in total fecal gram-negative bacteria (p > 0.05) but showed an increasing level of trimethoprim (TMP) resistance (p students. These 18 TMP-resistant E. coli were also resistant to ampicillin (44%), azithromycin (11%), chloramphenicol (39%), ciprofloxacin (11%), doxycycline (89%), erythromycin (100%), furazolidone (72%), levofloxacin (17%), trimethoprim-sulfamethoxazole (89%) and trovafloxacin (17%). In the absence of prophylactic and therapeutic antibiotics, increased acquisition of TMP-resistant gram-negative fecal flora in this developing country is probably due to poor sanitary conditions and the recurrent and heavy exposure to antimicrobial-resistant indigenous flora as a result of contaminated food and drink.

Signaling pathways regulating murine pancreatic development

DEFF Research Database (Denmark)

Serup, Palle

2012-01-01

The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...... been identified and the specific roles have been investigated by genetic and cell biological methods. The present review presents an overview of the principal signaling pathways involved in regulating murine pancreatic growth, morphogenesis, and cell differentiation....

Understanding trade pathways to target biosecurity surveillance

Directory of Open Access Journals (Sweden)

Manuel Colunga-Garcia

2013-09-01

Full Text Available Increasing trends in global trade make it extremely difficult to prevent the entry of all potential invasive species (IS. Establishing early detection strategies thus becomes an important part of the continuum used to reduce the introduction of invasive species. One part necessary to ensure the success of these strategies is the determination of priority survey areas based on invasion pressure. We used a pathway-centred conceptual model of pest invasion to address these questions: what role does global trade play in invasion pressure of plant ecosystems and how could an understanding of this role be used to enhance early detection strategies? We concluded that the relative level of invasion pressure for destination ecosystems can be influenced by the intensity of pathway usage (import volume and frequency, the number and type of pathways with a similar destination, and the number of different ecological regions that serve as the source for imports to the same destination. As these factors increase, pressure typically intensifies because of increasing a propagule pressure, b likelihood of transporting pests with higher intrinsic invasion potential, and c likelihood of transporting pests into ecosystems with higher invasibility. We used maritime containerized imports of live plants into the contiguous U.S. as a case study to illustrate the practical implications of the model to determine hotspot areas of relative invasion pressure for agricultural and forest ecosystems (two ecosystems with high potential invasibility. Our results illustrated the importance of how a pathway-centred model could be used to highlight potential target areas for early detection strategies for IS. Many of the hotspots in agricultural and forest ecosystems were within major U.S. metropolitan areas. Invasion ecologists can utilize pathway-centred conceptual models to a better understand the role of human-mediated pathways in pest establishment, b enhance current

POSSIBLE PREDICTORS OF ATRIAL FIBRILLATION RECURRENCE IN LONG-TERM PROPHYLACTIC PROPAFENONE THERAPY

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R. D. Kurbanov

2015-12-01

Full Text Available Aim. To identify possible predictors of atrial fibrillation (AF recurrence in 6-month prophylactic propafenone therapy. Material and methods. Patients (n=63; aged 52.2±12.6 years; 25.4% women with frequent AF recurrences who restored sinus rhythm with propafenone, were included into the study. Paroxysmal AF was observed in 84.1% of patients, and persistent AF — in 15.9% of patients. ECG, transthoracic echocardiography , chest radiography with the calculation of cardio-thoracic index (CTI was performed at baseline. All patients received rpropafenone therapy (450–600 mg/day during 6 months after sinus rhythm conversion. ECG and 24-hours ECG monitoring were performed in 1, 3 and 6 months of the therapy. Patients with 70–100% reduction in AF recurrence rate were included into the 1-st group, and patients with <70% reduction – into the 2-nd group. Results. 92%, 88.5% and 78% of patients were included into the group 1 after 1, 3 and 6 months of follow up, respectively. AF recurrences were observed 4.5, 3.8, and 1.7 times more often in women than these in men after 1, 3 and 6 months, respectively , (p>0.05. Mean age of patients in the group 2 was significantly older than this in patients of the group 1 (p<0.05. CTI, left atrium size and volume, interventricular septum thickness (IVST were significantly larger in group 2. Myocardium mass of the left ventricle (MMLV after 6 months of therapy was larger by 13.9% in patients of the group 2 vs this in patients of the group 1 (p<0.05. Conclusion. Insufficient preventive effect of propafenone was observed in 8%, 11.5% and 22% of patients in 1, 3 and 6 months of the follow-up, respectively. Propafenone prophylactic efficacy was slightly higher in men and younger patients. Patients with poor preventive effect of propafenone had a significantly larger baseline CTI, size and volume of the left atrium, IVST, and MMLV.

Cognition and Emotions in Recurrent Depressive Disorders - The Role of Inflammation and the Kynurenine Pathway.

Science.gov (United States)

Talarowska, Monika; Galecki, Piotr

2016-01-01

Separating emotions from cognition seems impossible in everyday experiences of a human being. Emotional processes have an impact on the ability of planning and solving problems, or decision-making skills. They are a valuable source of information about ourselves, our partners in interactions and the surrounding world. Recent years have shown that axial symptoms of depression are caused by emotion regulation disorders, dysfunctions in the reward system and deficits of cognitive processes. There is a few studies concerning a link between emotional and inflammatory processes in depression. The aim of this article is to present results of contemporary research studies over mutual connections between social cognition, cognitive processes and inflammatory factors significant for the aetiology of recurrent depressive disorders, with particular reference to the role of kynurenine pathways.

DNA interstrand cross-link repair: understanding role of Fanconi anemia pathway and therapeutic implications.

Science.gov (United States)

Shukla, Pallavi; Solanki, Avani; Ghosh, Kanjaksha; Vundinti, Babu Rao

2013-11-01

Interstrand cross-links (ICLs) are extremely toxic DNA lesions that prevent DNA double-helix separation due to the irreversible covalent linkage binding of some agents on DNA strands. Agents that induce these ICLs are thus widely used as chemotherapeutic drugs but may also lead to tumor growth. Fanconi anemia (FA) is a rare genetic disorder that leads to ICL sensitivity. This review provides update on current understanding of the role of FA proteins in repairing ICLs at various stages of cell cycle. We also discuss link between DNA cross-link genotoxicity caused by aldehydes in FA pathway. Besides this, we summarize various ICL agents that act as drugs to treat different types of tumors and highlight strategies for modulating ICL sensitivity for therapeutic interventions that may be helpful in controlling cancer and life-threatening disease, FA. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transition pathways for a UK low carbon electricity future

International Nuclear Information System (INIS)

Foxon, Timothy J.

2013-01-01

Achieving long-term targets for greenhouse gas emissions reductions, such as the UK's legally-binding target of reducing its emissions by 80% by 2050, will require a transition in systems for meeting and shaping energy service demands, involving radical substitution to low-carbon supply technologies and improvements in end-use energy efficiency. This paper describes the development and high-level analysis of a set of transition pathways to a UK low carbon electricity system, explaining key features of the core pathways developed and the distinctiveness and value of the approach. The pathways use an ‘action space’ concept to explore the dynamic interactions between choices made by actors, which are influenced by the competing governance ‘framings’ or ‘logics’ that different actors pursue. The paper sets out three core transition pathways – Market Rules, Central Co-ordination and Thousand Flowers, in which market, government and civil society logics respectively dominate. It summarises the key technological and institutional changes in these pathways, and the roles of actors in bringing these about. This leads to an identification of the key risks to the realisation of each of the pathways, and of the challenges for individuals, businesses, social movements and policy-makers in taking action to bring them about and sustain them. - Highlights: ► Development of a set of transition pathways to a UK low carbon electricity system. ► Action space to explore the dynamic interactions between choices made by actors. ► Three core pathways in which market, government and civil society logics dominate. ► Key technological and institutional changes, and the roles of actors in pathways. ► Challenges for different actors in realising pathways.

Radioinduced intestinal fibrosis: from molecular mechanisms to therapy applications. Contribution of the TGF--β1, of the CTGF and of the transduction pathway of the Rho/ROCK signal

International Nuclear Information System (INIS)

Haydont, V.

2006-12-01

Delayed radiation enteritis is an intestinal fibrosis induced by accidental or therapeutic radiation for pelvic and abdominal cancer treatments. Studies of molecular mechanisms involved in the development and maintenance of fibrosis have showed the respective contribution of CTGF, low TGF-β1 concentrations and Rho/ROCK pathway. Thus, based on the relationship between CTGF, TGF-β1 and Rho pathway, 2 therapeutics strategies have been develop. First, a pravastatin curative gift leads to a fibro-lysis involving an inhibition of Rho and in cascade a reduction of CTGF expression and extracellular matrix deposition. The data suggest that reversal of established radiation fibrosis in the gut is possible. Second, a pravastatin prophylactic gift prevents the installation of a chronic fibrosis but does not protect the tumor. On the base of these results, the radiation therapy department of the Institut Gustave Roussy will soon initiate 2 clinical trials. (author)

Prediction of bleeding and prophylactic platelet transfusions in cancer patients with thrombocytopenia

DEFF Research Database (Denmark)

Vinholt, Pernille J; Alnor, Anne; Nybo, Mads

2016-01-01

Studies on markers for bleeding risk among thrombocytopenic cancer patients are lacking. This prospective observational cohort study investigated whether platelet parameters and a standardised bleeding questionnaire predicted bleeding or prophylactic platelet transfusions in patients with cancer ...... platelet transfusion but not bleeding. Bleeding risk factors were previous haematuria or gastrointestinal bleeding, infection, antiplatelet or anticoagulant treatment, high urea nitrogen, low haemoglobin or high creatinine....... or warfarin OR = 2.34, 95% CI 1.23–4.48; urea nitrogen OR = 1.15, 95% CI 1.07–1.25; creatinine OR = 1.01, 95% CI 1.01–1.01; and haemoglobin OR = 0.62, 95% CI 0.41–0.93. Specific information regarding previous gastrointestinal bleeding OR = 3.33, 95% CI 1.19–9.34 and haematuria OR = 3.00, 95% CI 1...

Participation in two phase II prophylactic HIV vaccine trials in the UK.

Science.gov (United States)

Gray, Kimberly; Legg, K; Sharp, A; Mackie, N; Olarinde, F; De Souza, C; Weber, J; Peters, B

2008-06-02

There will be a continued imperative to recruit large numbers of healthy volunteers to early phase prophylactic HIV vaccine (PHV) trials. We studied mechanisms associated with participation in two related phase II PHV trials. The most cited reasons for volunteering were altruism and a personal connection to HIV. The most successful recruiting strategies targeted organisations dealing with HIV, health or social issues, or were directed to large audiences through the mass media. However, circulated emails and word of mouth were the most resource-effective approaches. Group discussions and the collection of a pool of potential volunteers were much less effective than one-to-one discussions and immediate screening after recruitment. We utilised our findings to devise key recommendations to assist PHV trial teams who are planning future studies.

Systematic Review and Meta-Analysis of Randomized Controlled Trials Evaluating Prophylactic Intra-Operative Wound Irrigation for the Prevention of Surgical Site Infections

NARCIS (Netherlands)

de Jonge, Stijn W.; Boldingh, Quirine J. J.; Solomkin, Joseph S.; Allegranzi, Benedetta; Egger, Matthias; Dellinger, E. Patchen; Boermeester, Marja A.

2017-01-01

Surgical site infections (SSIs) are one of the most common hospital-acquired infections. To reduce SSIs, prophylactic intra-operative wound irrigation (pIOWI) has been advocated, although the results to date are equivocal. To develop recommendations for the new World Health Organization (WHO) SSI

PROPHYLACTIC ENDOSCOPIC INJECTION SCLEROTHERAPY FOR GASTRIC VARICES : 1. DEVELOPMENT OF A NEW SCLEROTHERAPY TECHNIQUE AND ITS APPLICATION

OpenAIRE

Matsumura, Masahiko

1994-01-01

The author designed a direct injection method of endoscopic injection sclerotherapy (EIS) for gastric varices with a newly developed technique for controlling bleeding from the punctured site, and subsequently used it for prophylactic treatment in 10 cases. EIS was performed under X-ray monitoring in the absence of a balloon, and 5% ethanolamine oleate containing 49% Iopamidol was used as the sclerosant. A twenty-five gauge needle wearing an outer tube was used for the puncture. After injecti...

Role of the RecF pathway of recombination in the metabolism of uv-irradiated DNA in Escherichia coli K-12

International Nuclear Information System (INIS)

Rothman, R.H.

1976-01-01

The RecF pathway of genetic recombination in Escherichia coli is potentially capable of supporting wild type levels of recombination, but in wild type cells it plays a relatively minor role in this process. RecF and recL single mutants were found to be ultraviolet-sensitive but recombination proficient. These observations led to the hypothesis that the main function of the RecF pathway lies in the metabolism of uv-damaged DNA. The role of reF and recL in pathways of recovery from uv-irradiation has been examined. Both recF - and recL - inhibited post-replication joining of DNA fragments synthesized on uv-damaged DNA templates (post-replication repair). The addition of a uvrB5 mutation to the single mutants did not affect the cell's ability to complete post-replication repair in the case of recL, but did completely prevent completion of joining in the case of recF. It was hypothesized that recF is an endonuclease weakly indirectly suppressible by the presence of functional correndo II. It is suggested that recF is necessary to cleave the crossed strand intermediate at the end of repair. RecL, in addition to its involvement in post-replication repair, was also found to be involved in excision repair. A uvrB recB recC recF multiple mutant was as sensitive as a uvrB recA strain, suggesting that it is devoid of any repair abilities. RecB - was shown to have an inhibitory effect of post-replication repair. The uvrB recF mutant, however, was totally devoid of post-replication repair even though recB + contributed to the recovery of the strain. Thus the role of recB in post-replication repair is unclear. Lastly, the effects of recF and recL on uv-inducible repair was studied. W-reactivation of uv-irradiated lambda was used as an assay for inducible repair. The conclusions from these experiments were unclear. They seemed to imply that W-reactivation is effected by the combined action of excision repair and post-replication repair

Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A.

Science.gov (United States)

Collins, P W; Blanchette, V S; Fischer, K; Björkman, S; Oh, M; Fritsch, S; Schroth, P; Spotts, G; Astermark, J; Ewenstein, B

2009-03-01

The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level break-through bleeding in patients with severe hemophilia A on prophylaxis. This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. These data have important implications for the management of patients with severe hemophilia.

Radio-prophylactic treatment with imidazole and/or Serotonin for Modulation of Tissue Catecholamines in whole body gamma irradiated Rats

International Nuclear Information System (INIS)

Hassan, S.H.M.; Roushdy, H.M.; Maklaad, Y.A.; El-Sayed, M.E.

1995-01-01

The present study has been conducted to evaluate the radioprotective effects of imidazole, serotonin and their combination on radiation induced reduction in catecholamine contents of the heart and adrenal glands in albino rat. The contribution of catecholamines in the radioprotective role of these agents has been evaluated. Whole-body gamma-irradiation (6 Gy) induced a significant reduction in heart and adrenal glands contents of catecholamine (epinephrine, norepinephrine and dopamine) one day post irradiation. Such reduction in catecholamine contents was more pronounced on the seventh day post exposure. Administration of imidazole (350 mg kg-1) or serotonin. (15 mg. kg-1) controlled the radiation induced reduction in catecholamine contents of heart as well as adrenal glands. Whereas, combination of imidazole (17 mg kg-1) serotonin (15 mg. kg-1) afforded a better protection than either agent given alone, in view that all the measured parameters could be fully restored to the values pre-irradiation. This study appreciate the usage of such combination as a prophylactic treatment for controlling the stress-state induced by irradiation which is associated with disturbed level of endogenous catecholamine contents in those sensitive patients undergoing radiotherapy. 2 tabs

Molecular pathways: the role of NR4A orphan nuclear receptors in cancer.

LENUS (Irish Health Repository)

Mohan, Helen M

2012-06-15

Nuclear receptors are of integral importance in carcinogenesis. Manipulation of classic ligand-activated nuclear receptors, such as estrogen receptor blockade in breast cancer, is an important established cancer therapy. Orphan nuclear receptors, such as nuclear family 4 subgroup A (NR4A) receptors, have no known natural ligand(s). These elusive receptors are increasingly recognized as molecular switches in cell survival and a molecular link between inflammation and cancer. NR4A receptors act as transcription factors, altering expression of downstream genes in apoptosis (Fas-ligand, TRAIL), proliferation, DNA repair, metabolism, cell migration, inflammation (interleukin-8), and angiogenesis (VEGF). NR4A receptors are modulated by multiple cell-signaling pathways, including protein kinase A\\/CREB, NF-κB, phosphoinositide 3-kinase\\/AKT, c-jun-NH(2)-kinase, Wnt, and mitogen-activated protein kinase pathways. NR4A receptor effects are context and tissue specific, influenced by their levels of expression, posttranslational modification, and interaction with other transcription factors (RXR, PPAR-Υ). The subcellular location of NR4A "nuclear receptors" is also important functionally; novel roles have been described in the cytoplasm where NR4A proteins act both indirectly and directly on the mitochondria to promote apoptosis via Bcl-2. NR4A receptors are implicated in a wide variety of malignancies, including breast, lung, colon, bladder, and prostate cancer; glioblastoma multiforme; sarcoma; and acute and\\/or chronic myeloid leukemia. NR4A receptors modulate response to conventional chemotherapy and represent an exciting frontier for chemotherapeutic intervention, as novel agents targeting NR4A receptors have now been developed. This review provides a concise clinical overview of current knowledge of NR4A signaling in cancer and the potential for therapeutic manipulation.

PROPHYLACTIC EFFECTIVENESS OF FUSAFUNGINE IN CHILDREN WITH CHRONIC TONSILLITIS

Directory of Open Access Journals (Sweden)

T.I. Garashchenko

2010-01-01

Full Text Available In 2008/2009, at the time of influenza epidemic, the study of ambulatory prophylactic treatment of fusafungine (Bioparox in 50 children 7–15 years old with chronic tonsillitis was performed. All these children underwent regular ENT check-up. The control group included 50 schoolchildren the same age without chronic diseases of upper airways. After the treatment with intranasal fusafungine, the amount of patients with Streptococcus pyogenes was decreased 1,6 times low (and after 3 months of treatment it was decreased 3,5 times low. The sanation of palatine tonsils from Candida albicans was detected (eradication of microorganism was achieved in 58% of cases, and the amount of patients with pharyngomycosis was decreased 2,4 times low. Patient’s quality of life significantly increased, and ENT-specialists met less complaints (in 4,5–15 times low. The morbidity with respiratory infections in 3 months after the treatment with fusafungine was 7,5 times low than in control group.Key words: schoolchildren, chronic tonsillitis, acute respiratory infection, fusafungine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(1:26-31

Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway.

Science.gov (United States)

Kambe, Taiho; Matsunaga, Mayu; Takeda, Taka-Aki

2017-10-19

More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.

Pathway Distiller - multisource biological pathway consolidation.

Science.gov (United States)

Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

2012-01-01

One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

Prophylactic Use of Oral Dexamethasone to Alleviate Fatigue During Regorafenib Treatment for Patients With Metastatic Colorectal Cancer.

Science.gov (United States)

Fukuoka, Shota; Shitara, Kohei; Noguchi, Masaaki; Kawazoe, Akihito; Kuboki, Yasutoshi; Bando, Hedeaki; Okamoto, Wataru; Kojima, Takashi; Doi, Toshihiko; Ohtsu, Atsushi; Yoshino, Takayuki

2017-06-01

Fatigue is the most common toxicity of all grade toxicities with regorafenib, was the second most common toxicity in the CORRECT (regorafenib monotherapy for previously treated metastatic colorectal cancer) study, and is a major reason for early dose modification. The results from a recent randomized study suggested that dexamethasone (DEX) can improve cancer-related fatigue. We retrospectively analyzed the effect of prophylactic use of an oral DEX on fatigue during regorafenib treatment in patients with metastatic colorectal cancer (mCRC). A total of 105 patients who had received regorafenib at our institution from May 2013 to August 2014 were divided into 2 groups according to oral DEX use (2 mg/day; at the physician's discretion). Of the 105 patients, 31 received prophylactic DEX and 74 received regorafenib alone. The time to dose modification was significantly longer in the DEX group than in the no DEX group (15 days vs. 9 days; P = .009). The incidence of fatigue (grade ≥ 1) was significantly lower with DEX than without DEX (25.8% vs. 50.0%; P = .022). Fewer patients experienced a decreased appetite (grade ≥ 1; 3.2% vs. 35.1%; P regorafenib treatment, resulting in prolonging the time to dose modification for regorafenib. The decreased incidence of appetite loss and HFSR also suggest that concurrent DEX administration with regorafenib warrants further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

Prophylactic Potential of Synbiotic (Lactobacillus casei and Inulin) in Malnourished Murine Giardiasis: an Immunological and Ultrastructural Study.

Science.gov (United States)

Shukla, Geeta; Sharma, Anuj; Bhatia, Ruchika; Sharma, Mridul

2017-12-19

Giardiasis is a re-emerging infectious disease with outbreaks reported globally specially in children and malnourished individuals leading to malabsorption, growth retardation, and severe diarrhea. Thus, in the present study, prophylactic administration of synbiotic as the functional food was used to assess its antigiardial potential in malnourished murine giardiasis. Interestingly, prior administration of synbiotic (Lactobacillus casei + inulin) even to malnourished-Giardia-infected mice led to increased body mass, small intestine mass, lactobacilli counts, and reduced severity of giardiasis as evident by decreased cyst and trophozoite counts. Synbiotic therapy further boosted the innate and acquired immune response resulting into increase in nitric oxide, antigiardial secretory IgA and IgG antibody levels along with IL-6 and IL-10 cytokines, and decreased levels of inflammatory TNF-α cytokine in both serum and intestinal fluid in malnourished-synbiotic-Giardia-infected mice compared with malnourished-Giardia-infected mice. More specifically, histopathological and scanning electron microscopy analysis of the small intestine also confirmed the modulatory potentials of synbiotic in malnourished-synbiotic-Giardia mice which had less cellular and mucosal damage compared with severely damaged, mummified, and blunted villi in malnourished-Giardia-infected mice. Taken together, this is the first experimental study to report that prior supplementation of synbiotic restored the gut morphology and improved the immune status of the malnourished-Giardia-infected mice, and could be considered as the prophylactic adjunct therapy for malnourished individuals.

Postsurgical recurrence of ileal Crohn's disease: an update on risk factors and intervention points to a central role for impaired host-microflora homeostasis.

LENUS (Irish Health Repository)

Cunningham, Michael F

2010-07-01

A pressing need exists to identify factors that predispose to recurrence after terminal ileal resection for Crohn\\'s disease (CD) and to determine effective prophylactic strategies. This review presents an up-to-date summary of the literature in the field and points to a role for bacterial overproliferation in recurrence.

Role of GSK-3β in Regulation of Canonical Wnt/β-catenin Signaling and PI3-K/Akt Oncogenic Pathway in Colon Cancer.

Science.gov (United States)

Jain, Shelly; Ghanghas, Preety; Rana, Chandan; Sanyal, S N

2017-08-09

Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway.

RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway.

Directory of Open Access Journals (Sweden)

Angela M Keuling

Full Text Available BACKGROUND: Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10 activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity.

Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy.

Science.gov (United States)

Marques, Camila; Licks, Francielli; Zattoni, Ingrid; Borges, Beatriz; de Souza, Luiz Eduardo Rizzo; Marroni, Claudio Augusto; Marroni, Norma Possa

2013-07-28

peroxynitrite. Glutamine treatment demonstrated to reduce oxidative damage but does not reduce angiogenesis induced by PH in gastric tissue, demonstrating a beneficial role for the PI3K-Akt-eNOS pathway.

Role of the nitric oxide/cyclic GMP/Ca2+ signaling pathway in the pyrogenic effect of interleukin-1beta.

Science.gov (United States)

Palmi, Mitri; Meini, Antonella

2002-04-01

Interleukin-1beta (IL-1beta) has a wide spectrum of inflammatory, metabolic, haemopoietic, and immunological properties. Because it produces fever when injected into animals and humans, it is considered an endogenous pyrogen. There is evidence to suggest that Ca2+ plays a critical role in the central mechanisms of thermoregulation, and in the intracellular signaling pathways controlling fever induced by IL-1beta and other pyrogens. Data from different labs indicate that Ca2+ and Na+ determine the temperature set point in the posterior hypothalamus (PH) of various mammals and that changes in Ca2+ and PGE2 concentrations in the cerebrospinal fluid (CSF) of these animals are associated with IL-1beta-induced fever. Antipyretic drugs such as acetylsalicylic acid, dexamethasone, and lipocortin 5-(204-212) peptide counteract IL-1beta-induced fever and abolish changes in Ca2+ and PGE2 concentrations in CSF. In vitro studies have established that activation of the nitric oxide (NO)/cyclic GMP (cGMP) pathway is part of the signaling cascade transducing Ca2+ mobilization in response to IL-1beta and that the ryanodine (RY)- and inositol-(1,4,5)-trisphosphate (IP3)-sensitive pools are the main source of the mobilized Ca2+. It is concluded that the NO/cGMP/Ca2+ pathway is part of the signaling cascade subserving some of the multiple functions of IL-1beta.

Endocytic pathways involved in PLGA nanoparticle uptake by grapevine cells and role of cell wall and membrane in size selection.

Science.gov (United States)

Palocci, Cleofe; Valletta, Alessio; Chronopoulou, Laura; Donati, Livia; Bramosanti, Marco; Brasili, Elisa; Baldan, Barbara; Pasqua, Gabriella

2017-12-01

PLGA NPs' cell uptake involves different endocytic pathways. Clathrin-independent endocytosis is the main internalization route. The cell wall plays a more prominent role than the plasma membrane in NPs' size selection. In the last years, many studies on absorption and cell uptake of nanoparticles by plants have been conducted, but the understanding of the internalization mechanisms is still largely unknown. In this study, polydispersed and monodispersed poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs) were synthesized, and a strategy combining the use of transmission electron microscopy (TEM), confocal analysis, fluorescently labeled PLGA NPs, a probe for endocytic vesicles (FM4-64), and endocytosis inhibitors (i.e., wortmannin, ikarugamycin, and salicylic acid) was employed to shed light on PLGA NP cell uptake in grapevine cultured cells and to assess the role of the cell wall and plasma membrane in size selection of PLGA NPs. The ability of PLGA NPs to cross the cell wall and membrane was confirmed by TEM and fluorescence microscopy. A strong adhesion of PLGA NPs to the outer side of the cell wall was observed, presumably due to electrostatic interactions. Confocal microscopy and treatment with endocytosis inhibitors suggested the involvement of both clathrin-dependent and clathrin-independent endocytosis in cell uptake of PLGA NPs and the latter appeared to be the main internalization pathway. Experiments on grapevine protoplasts revealed that the cell wall plays a more prominent role than the plasma membrane in size selection of PLGA NPs. While the cell wall prevents the uptake of PLGA NPs with diameters over 50 nm, the plasma membrane can be crossed by PLGA NPs with a diameter of 500-600 nm.

Effect of prophylactic digitalization on the development of myocardial hypertrophy.

Science.gov (United States)

Cutilletta, A F; Rudnik, M; Arcilla, R A; Straube, R

1977-11-01

The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

Prophylactic treatment of hereditary severe factor VII deficiency in pregnancy.

Science.gov (United States)

Pfrepper, Christian; Siegemund, Annelie; Hildebrandt, Sven; Kronberg, Juliane; Scholz, Ute; Niederwieser, Dietger

2017-09-01

: Severe hereditary factor VII deficiency is a rare bleeding disorder and may be associated with a severe bleeding phenotype. We describe a pregnancy in a 33-year-old woman with compound heterozygous factor VII deficiency and a history of severe menorrhagia and mucocutaneous bleedings. After discontinuation of contraceptives, menstruation was covered with recombinant activated factor VII (rFVIIa), and during pregnancy, rFVIIa had to be administered in first trimester in doses ranging from 15 to 90 μg/kg per day because of recurrent retroplacental hematomas and vaginal bleedings. Thrombin generation was measured in first trimester at different doses of rFVIIa and showed an increase in lag time when doses of less than 30 μg/kg/day were administered, whereas time to thrombin peak and peak thrombin were not influenced. A low-dose rFVIIa prophylactic treatment of 15 μg/kg every other day in the late second and in the third trimester was sufficient to allow a successful childbirth in this patient with severe factor VII deficiency.

Recruitment barriers for prophylactic vaccine trials: A study in Belgium.

Science.gov (United States)

Harrington, Lauriane; Van Damme, Pierre; Vandermeulen, Corinne; Mali, Stéphanie

2017-12-04

Recruitment of volunteers is one of the main challenges in clinical trial management, and there is little information about recruitment barriers for preventative vaccine trials. We investigated both the recruitment barriers and recruitment strategies for preventive vaccine trials in Belgium. A 10 min survey was used as well as interviews of staff at all clinical trial sites in Belgium that regularly perform vaccine trials. We observed that there are successful recruitment strategies and few recruitment issues for trials involving healthy adults and those over 65 years old. However, challenges face the recruitment of paediatric populations, pregnant women, patients and the very elderly (over 85 years old). From these results, we identified three priority areas to increase recruitment for prophylactic vaccine trials in Belgium. These are: the lack of public knowledge about infectious diseases; the lack of resources of healthcare professionals to take part in clinical trials; and the burden to potential volunteers to take part in a trial. These were discussed with stakeholders and solutions were proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Environmental pathways of radioactivity to man

International Nuclear Information System (INIS)

Johns, T.F.

1983-01-01

An attempt has been made to discuss environmental pathways and their significance in a way which will be understood by non-specialists. The role of these pathways in the general structure of radiological protection is explained and the more important pathways to man from releases into the air and the aquatic environment are discussed generally. The various mechanisms which lead to the dispersion or reconstruction of radioactive materials are discussed and their importance stressed. The more important pathways for particular groups of radionuclides from the nuclear power industry are dealt with in detail and information resulting from many theoretical and practical studies of the situations at particular locations summarized. There is detailed discussion about the doses to local population groups and about worldwide doses as a result of the release of certain long-lived radioactive species. The corresponding pathways and resulting doses from natural radiation are detailed to illustrate that the doses from the nuclear power industry are small in comparison, and brief consideration is given to animal and plant doses from the industry. (U.K.)

Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

International Nuclear Information System (INIS)

Schoenfeld, Gordon O.; Amdur, Robert J.; Schmalfuss, Ilona M.; Morris, Christopher G.; Keole, Sameer R.; Mendenhall, William M.; Marcus, Robert B.

2006-01-01

Purpose: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Methods and Materials: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. Results: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Conclusions: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element

[Yin Care--a natural product for prophylactics and treatment of vaginal infections].

Science.gov (United States)

Mikhova, M; Batashki, I; Ivanov, St

2007-01-01

A prospective study, including 60 patients with vaginal discharge has been made at Maternity hospital "Majchin dom"--Sofia for the period November 2006- February 2007. In 32 patients no causative agent has been revealed. They have been counseled to use Yin Care--vaginal lotion for 3 months in prophylactic concentration. 88.4% reported for diminished discharge. No adverse effects have been observed. In 11 patients suffering from bacterial vaginitis, caused by S. Epidermidis, S. Aureus, Enterococcus and E. Coli cure was achieved in 72.7% of cases. 17 women with Candida vaginitis have been included in the study. After standard antifungal treatment, 8 of them continued therapy with Yin Care. Recurrence of disease has been observed in only one case, while in the group treated with antifungal medication only recurrence has been observed in 2 cases.

Evaluation of post-operative prophylactic irradiation for carcinoma of the esophagus

International Nuclear Information System (INIS)

Mafune, Ken-ichi; Tanaka, Yoichi; Fujita, Kichishiro; Sakura, Mizuyoshi

1987-01-01

Of 147 patients with carcinoma of the esophagus resected at Saitama Cancer Center Hospital for 10 years, 98 cases were studied to evaluate post-operative prophylactic irradiation. The total dose of irradiation was up to 4,000 ∼ 5,000 rads of Linac X-ray and the irradiated field was T-shaped covering the upper mediastinal and bilateral cervical regions. The prognosis of the post-operative irradiated group (56 cases) was significantly better than that of the control group (42 cases) (p < 0.01). This study resulted in a five-year survival rate of 34.2 percent for patients in the post-operative irradiated group, compared to 16.7 percent for those in the control group. Further detailed comparative studies revealed similar results. Cancer recurrence occurred at the irradiated fields in 8 cases (14.3 %), though in 15 cases (35.7 %) of the control group. This suggested the local suppressive effect of the post-operative irradiation to the cancer recurrence. (author)

An overview of adjuvants utilized in prophylactic vaccine formulation as immunomodulators.

Science.gov (United States)

Chauhan, Nidhi; Tiwari, Sukirti; Iype, Tessy; Jain, Utkarsh

2017-05-01

Development of efficient and cost effective vaccines have been recognized as the primary concern to improve the overall healthcare in a country. In order to achieve this goal, more improved and powerful adjuvants need to be developed. Lacking in the self-adjuvanting immuno-modulatory constituents, vaccines exhibit lower immunogenicity. Combining potent adjuvants with vaccines is the most appropriate method to enhance the efficacy of the vaccines. Hence, this review is focussed on the most potent adjuvants for the formulation of vaccines. Areas covered: This review focuses on Oil-based emulsions, Mineral compounds, Liposomes, Bacterial products, ISCOMs and most recently used nanomaterials as adjuvants for enhancing the antigenicity of vaccines. Furthermore, this review explains the immunological response elicited by various particles. Moreover, case studies are incorporated providing an in depth analyses of various adjuvant-containing vaccines which are currently used. Expert commentary: Enhanced fundamental knowledge about the adjuvants and their immuno-stimulatory capabilities and delivery mechanisms will facilitate the rational designing of prophylactic vaccines with better efficacy.

[Intermittent pneumatic compression of the lower extremity muscles in complex prophylactics of postoperative venous thromboses in elderly and senile patients].

Science.gov (United States)

Glushkov, N I; Openchenko, S V

2009-01-01

An analysis of frequency of venous thrombitic complications after different operations on 69 patients aged from 69 through 87 was made. The greatest number of venous thromboses was noted after amputations of the femur. Intermittent pneumatic compression of the lower extremities in addition to standard methods of prophylactics reduced the number of postoperative thromboses from 12.8% to 3.3%.

Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: Protective role of arjunolic acid

International Nuclear Information System (INIS)

Manna, Prasenjit; Ghosh, Jyotirmoy; Das, Joydeep; Sil, Parames C.

2010-01-01

Present study investigates the beneficial role of arjunolic acid (AA) against the alteration in the cytokine levels and simultaneous activation of oxidative stress responsive signaling pathways in spleen under hyperglycemic condition. Diabetes was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body weight, injected in the tail vain). STZ administration elevated the levels of IL-2 as well as IFN-γ and attenuated the level of TNF-α in the sera of diabetic animals. In addition, hyperglycemia is also associated with the increased production of intracellular reactive intermediates resulting with the elevation in lipid peroxidation, protein carbonylation and reduction in intracellular antioxidant defense. Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IκBα and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue. Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death. Histological examination revealed that diabetic induction depleted the white pulp scoring which is in agreement with the reduced immunological response. Treatment with AA prevented the hyperglycemia and its associated pathogenesis in spleen tissue. Results suggest that AA might act as an anti-diabetic and immunomodulatory agent against hyperglycemia.

The effect of prophylactic intravenous tranexamic acid on blood loss after vaginal delivery in women at low risk of postpartum haemorrhage: a double-blind randomised controlled trial.

Science.gov (United States)

Mirghafourvand, Mojgan; Mohammad-Alizadeh, Sakineh; Abbasalizadeh, Fatemeh; Shirdel, Mina

2015-02-01

To determine the effect of prophylactic tranexamic acid (TA) on calculated and measured blood loss after vaginal delivery in women at low risk of postpartum haemorrhage. In this double-blind randomised controlled trial, 120 women with a singleton pregnancy were randomly allocated to receive either one gram intravenous TA or placebo in addition to 10 IU oxytocin after delivery of the fetus. Calculated blood loss was determined based on haematocrit before delivery and 12-24 h postdelivery. The quantity of blood loss was measured during two time periods: from delivery of the fetus to placental expulsion and from placental expulsion to the end of the second hour after childbirth. The mean (SD) calculated total blood loss (519 (320) vs 659 (402) mL, P = 0.036) and measured blood loss from placental delivery to 2 h postpartum (69 (39) vs 108 (53) mL, P  1000 mL was lower in the TA group (7% vs 18%, P = 0.048). Prophylactic TA reduces blood loss after vaginal delivery in women with a low risk of postpartum haemorrhage. The prophylactic use of TA may reduce blood loss complications and enhance maternal health. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

The Glymphatic Pathway.

Science.gov (United States)

Benveniste, Helene; Lee, Hedok; Volkow, Nora D

2017-01-01

The overall premise of this review is that cerebrospinal fluid (CSF) is transported within a dedicated peri-vascular network facilitating metabolic waste clearance from the central nervous system while we sleep. The anatomical profile of the network is complex and has been defined as a peri-arterial CSF influx pathway and peri-venous clearance routes, which are functionally coupled by interstitial bulk flow supported by astrocytic aquaporin 4 water channels. The role of the newly discovered system in the brain is equivalent to the lymphatic system present in other body organs and has been termed the "glymphatic pathway" or "(g)lymphatics" because of its dependence on glial cells. We will discuss and review the general anatomy and physiology of CSF from the perspective of the glymphatic pathway, a discovery which has greatly improved our understanding of key factors that control removal of metabolic waste products from the central nervous system in health and disease and identifies an additional purpose for sleep. A brief historical and factual description of CSF production and transport will precede the ensuing discussion of the glymphatic system along with a discussion of its clinical implications.

Critical nodes in signalling pathways

DEFF Research Database (Denmark)

Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

2006-01-01

Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

The role of the PI3K-Akt signal transduction pathway in Autographa californica multiple nucleopolyhedrovirus infection of Spodoptera frugiperda cells

International Nuclear Information System (INIS)

Xiao Wei; Yang Yi; Weng Qingbei; Lin Tiehao; Yuan Meijin; Yang Kai; Pang Yi

2009-01-01

Many viruses activate the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, thereby modulating diverse downstream signaling pathways associated with antiapoptosis, proliferation, cell cycling, protein synthesis and glucose metabolism, in order to augment their replication. To date, the role of the PI3K-Akt pathway in Baculovirus replication has not been defined. In the present study, we demonstrate that infection of Sf9 cells with Autographa californica multiple nucleopolyhedrovirus (AcMNPV) elevated cellular Akt phosphorylation at 1 h post-infection. The maximum Akt phosphorylation occurred at 6 h post-infection and remained unchanged until 18 h post-infection. The PI3K-specific inhibitor, LY294002, suppressed Akt phosphorylation in a dose-dependent manner, suggesting that AcMNPV-induced Akt phosphorylation is PI3K-dependent. The inhibition of PI3K-Akt activation by LY294002 significantly reduced the viral yield, including a reduction in budded viruses and occlusion bodies. The virus production was reduced only when the inhibitor was added within 24 h of infection, implying that activation of PI3K occurred early in infection. Correspondingly, both viral DNA replication and late (VP39) and very late (POLH) viral protein expression were impaired by LY294002 treatment; LY294002 had no effect on immediate-early (IE1) and early-late (GP64) protein expression. These results demonstrate that the PI3K-Akt pathway is required for efficient Baculovirus replication.

The Role of Institutional Placement, Family Conflict, and Homosexuality in Homelessness Pathways Among Latino LGBT Youth in New York City.

Science.gov (United States)

Castellanos, H Daniel

2016-01-01

Despite the overrepresentation of Lesbian, Gay, Bisexual, and Transgender (LGBT) youth among the homeless, the processes leading to their homelessness are understudied. This ethnographic study sought to elucidate the role of sexual orientation in the pathway to housing instability among young gay men. Fieldwork included 18 months of participant observations in public spaces and at a homeless LGBT youth organization in New York City, as well as formal semistructured interviews with 14 Latino young men and five staff. Three distinct pathways emerged. Some youth became homeless after placement in state systems of care disrupted their social support systems, while others became homeless after extreme family conflict over sexual orientation. Nonetheless, most youths became homeless as a result of long-term processes of family disintegration in which normative adolescent development and disclosure of homosexuality exacerbated preexisting conflict. These findings suggest the need to examine the accumulation of risks before disclosure exacerbates family conflict and increases their risk of homelessness.

Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect

NARCIS (Netherlands)

Mathijssen, N.C.J.; Masereeuw, R.; Holme, P.A.; Kraaij, M.G.J. van; Laros, B.A.P.; Peyvandi, F.; Heerde, W.L. van

2013-01-01

INTRODUCTION: Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. MATERIALS AND METHODS: Ten factor VII deficient patients

Body image and psychological distress after prophylactic mastectomy and breast reconstruction in genetically predisposed women: A prospective long-term follow-up study

NARCIS (Netherlands)

den Heijer, M.; Seynaeve, C.; Timman, R.; Duivenvoorden, H.J.; Vanheusden, K.; Tilanus-Linthorst, M.; Menke-Pluijmers, M.B.E.; Tibben, A.

2012-01-01

Purpose: To explore the course of psychological distress and body image at long-term follow-up (6-9 years) after prophylactic mastectomy and breast reconstruction (PM/BR) in women at risk for hereditary breast cancer, and to identify pre-PM risk factors for poor body image on the long-term. Methods:

Body image and psychological distress after prophylactic mastectomy and breast reconstruction in genetically predisposed women: a prospective long-term follow-up study.

NARCIS (Netherlands)

Heijer, M. den; Seynaeve, C.; Timman, R.; Duivenvoorden, H.J.; Vanheusden, K.; Tilanus-Linthorst, M.; Menke-Pluijmers, M.B.; Tibben, A.

2012-01-01

PURPOSE: To explore the course of psychological distress and body image at long-term follow-up (6-9 years) after prophylactic mastectomy and breast reconstruction (PM/BR) in women at risk for hereditary breast cancer, and to identify pre-PM risk factors for poor body image on the long-term. METHODS:

Targeting the Fanconi Anemia Pathway to Identify Tailored Anticancer Therapeutics

Directory of Open Access Journals (Sweden)

Chelsea Jenkins

2012-01-01

Full Text Available The Fanconi Anemia (FA pathway consists of proteins involved in repairing DNA damage, including interstrand cross-links (ICLs. The pathway contains an upstream multiprotein core complex that mediates the monoubiquitylation of the FANCD2 and FANCI heterodimer, and a downstream pathway that converges with a larger network of proteins with roles in homologous recombination and other DNA repair pathways. Selective killing of cancer cells with an intact FA pathway but deficient in certain other DNA repair pathways is an emerging approach to tailored cancer therapy. Inhibiting the FA pathway becomes selectively lethal when certain repair genes are defective, such as the checkpoint kinase ATM. Inhibiting the FA pathway in ATM deficient cells can be achieved with small molecule inhibitors, suggesting that new cancer therapeutics could be developed by identifying FA pathway inhibitors to treat cancers that contain defects that are synthetic lethal with FA.

Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

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Seyed Amir Dadkhahi

2017-05-01

Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes.

Science.gov (United States)

Mecacci, Federico; Simeone, Serena; Cirami, Calogero Lino; Cozzolino, Mauro; Serena, Caterina; Rambaldi, Marianna Pina; Gallo, Pamela; Emmi, Lorenzo; Cammelli, Daniele; Mello, Giorgio; Matucci Cerinic, Marco

2017-11-27

Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol. Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χ 2 -test (significant values when p 1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

Role of endogenous opioid peptides in the pathogenesis of motion sickness

International Nuclear Information System (INIS)

Yasnetsov, V.V.; Il'ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

1986-01-01

This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness

Role of endogenous opioid peptides in the pathogenesis of motion sickness

Energy Technology Data Exchange (ETDEWEB)

Yasnetsov, V.V.; Il' ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

1986-01-01

This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness.

Outcome of peri-anal surgeries without use of prophylactic antibiotics, in terms of post operative wound infection

International Nuclear Information System (INIS)

Asif, M.; Mirza, A.A.; Saeed, A.

2017-01-01

To determine the outcome of perianal surgeries without use of antibiotics in terms of post operative infection. Study Design: Descriptive study. Place and Duration of study: Department of general surgery, Pakistan Atomic Energy Commission General Hospital, from Jan 2014 to Jun 2015. Material and Methods: All patients, both male and female admitted for hemorrhoidectomy, fistulectomy and lateral internal sphincterotomy for Anal Fissure with minimum 02 months follow-up were included in the study through non probability consecutive sampling technique. The selected patients were not administered any antibiotics pre or postoperatively. All these patients were followed up for any post-operative surgical site infection up to 02 months. Patients were advised only to take pyodine sitz bath regularly. Results: One hundred and eighty two patients were selected for the study. Patients mean age was 48.0 +- 11.4 years. 68.68% were male and 31.3% were female patients. In our study most frequent clinical presentation was hemorrhoids (37.9.0%), followed by anal fissure (33.5%). Least frequent clinical presentation was of anal fistula (28.57%). None of the patients developed surgical site infection post operatively. Conclusions: In our study we found that there was no additional beneficial role of prophylactic antibiotics in perianal surgeries Perianal surgeries can safely be performed without the use pre or post-operative antibiotics there by significantly reducing health care expenses. (author)

Alternative pathways for angiotensin II generation in the cardiovascular system

Directory of Open Access Journals (Sweden)

C. Becari

2011-09-01

Full Text Available The classical renin-angiotensin system (RAS consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.

BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress.

Science.gov (United States)

Wei, Le; Kan, Li-Yuan; Zeng, Hai-Ying; Tang, Yi-Yun; Huang, Hong-Lin; Xie, Ming; Zou, Wei; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

2018-06-01

Our previous works have shown that hydrogen sulfide (H 2 S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H 2 S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H 2 S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H 2 S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H 2 S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H 2 S against CUMS-induced depressive-like behaviors.

EVALUATION OF EFFECTIVENESS OF HYPOALLERGENIC COMPOUND, ENRICHED WITH PREBIOTICS, FOR THE PROPHYLACTICS OF ATOPIC DERMATITIS

Directory of Open Access Journals (Sweden)

A.A. Dzhumagaziyev

2010-01-01

Full Text Available The article presents a study of prophylactic effectiveness of hypoallergenic compound «Nutrilon Hypoallergenic 1», fortified with prebiotics «IMMUNOFORTIS», in children from group of risk of development of atopic dermatitis. Anthropometric rates of children after 8 weeks of observation corresponded with average age rates; their physical development was estimated as harmonious. The compound was well-tolerated. Its use resulted in increase of bifido- and lactobacteria of intestinal micro flora and decrease of acute respiratory infections in infants.Key words: infants, alimentary allergy, atopic dermatitis, artificial feeding, prebiotics, hypoallergenic compound.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(1:37-43

Protein degradation pathways in Parkinson's disease: curse or blessing.

Science.gov (United States)

Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J

2012-08-01

Protein misfolding, aggregation and deposition are common disease mechanisms in many neurodegenerative diseases including Parkinson's disease (PD). Accumulation of damaged or abnormally modified proteins may lead to perturbed cellular function and eventually to cell death. Thus, neurons rely on elaborated pathways of protein quality control and removal to maintain intracellular protein homeostasis. Molecular chaperones, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are critical pathways that mediate the refolding or removal of abnormal proteins. The successive failure of these protein degradation pathways, as a cause or consequence of early pathological alterations in vulnerable neurons at risk, may present a key step in the pathological cascade that leads to spreading neurodegeneration. A growing number of studies in disease models and patients have implicated dysfunction of the UPS and ALP in the pathogenesis of Parkinson's disease and related disorders. Deciphering the exact mechanism by which the different proteolytic systems contribute to the elimination of pathogenic proteins, like α-synuclein, is therefore of paramount importance. We herein review the role of protein degradation pathways in Parkinson's disease and elaborate on the different contributions of the UPS and the ALP to the clearance of altered proteins. We examine the interplay between different degradation pathways and provide a model for the role of the UPS and ALP in the evolution and progression of α-synuclein pathology. With regards to exciting recent studies we also discuss the putative potential of using protein degradation pathways as novel therapeutic targets in Parkinson's disease.

Revisiting the slow force response: the role of the PKG signaling pathway in the normal and the ischemic heart.

Science.gov (United States)

Castro-Ferreira, Ricardo; Neves, João Sérgio; Ladeiras-Lopes, Ricardo; Leite-Moreira, André M; Neiva-Sousa, Manuel; Almeida-Coelho, João; Ferreira-Martins, João; F Leite-Moreira, Adelino

2014-09-01

The myocardial response to acute stretch consists of a two-phase increase in contractility: an acute increase by the Frank-Starling mechanism and a gradual and time-dependent increase in force generated known as the slow force response (SFR). The SFR is actively modulated by different signaling pathways, but the role of protein kinase G (PKG) signaling is unknown. In this study we aim to characterize the role of the PKG signaling pathway in the SFR under normal and ischemic conditions. Rabbit papillary muscles were stretched from 92 to 100% of maximum length (Lmax) under basal conditions, in the absence (1) or presence of: a PKG agonist (2) and a PKG inhibitor (3); under ischemic conditions in the absence (4) or presence of: a PKG agonist (5); a nitric oxide (NO) donor (6) and a phosphodiesterase 5 (PDE5) inhibitor (7). Under normoxia, the SFR was significantly attenuated by inhibition of PKG and remained unaltered with PKG activation. Ischemia induced a progressive decrease in myocardial contractility after stretch. Neither the PKG agonist nor the NO donor altered the myocardial response to stretch under ischemic conditions. However, the use of a PDE5 inhibitor in ischemia partially reversed the progressive deterioration in contractility. PKG activity is essential for the SFR. During ischemia, a progressive decline in the force is observed in response to acute myocardial stretch. This dysfunctional response can be partially reversed by the use of PDE5 inhibitors. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model.

Directory of Open Access Journals (Sweden)

Clément Guillou

Full Text Available To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1 or its immunodominant peptide (pEP1 to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way.Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight. Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP and anti-CII (total IgG and IgG1/IgG2a isotypes antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation.Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group.Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift.

Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model

Science.gov (United States)

Guillou, Clément; Derambure, Céline; Fréret, Manuel; Verdet, Mathieu; Avenel, Gilles; Golinski, Marie-Laure; Sabourin, Jean-Christophe; Loarer, François Le; Adriouch, Sahil; Boyer, Olivier; Lequerré, Thierry; Vittecoq, Olivier

2015-01-01

Objective To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way. Methods Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation. Results Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group. Conclusions Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift. PMID:26302382

Effect of Prophylactic Antifungal Protocols on the Prognosis of Liver Transplantation: A Propensity Score Matching and Multistate Model Approach

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Yi-Chan Chen

2016-01-01

Full Text Available Background. Whether routine antifungal prophylaxis decreases posttransplantation fungal infections in patients receiving orthotopic liver transplantation (OLT remains unclear. This study aimed to determine the effectiveness of antifungal prophylaxis for patients receiving OLT. Patients and Methods. This is a retrospective analysis of a database at Chang Gung Memorial Hospital. We have been administering routine antibiotic and prophylactic antifungal regimens to recipients with high model for end-stage liver disease scores (>20 since 2009. After propensity score matching, 402 patients were enrolled. We conducted a multistate model to analyze the cumulative hazards, probability of fungal infections, and risk factors. Results. The cumulative hazards and transition probability of “transplantation to fungal infection” were lower in the prophylaxis group. The incidence rate of fungal infection after OLT decreased from 18.9% to 11.4% (p=0.052; overall mortality improved from 40.8% to 23.4% (p<0.001. In the “transplantation to fungal infection” transition, prophylaxis was significantly associated with reduced hazards for fungal infection (hazard ratio: 0.57, 95% confidence interval: 0.34–0.96, p=0.033. Massive ascites, cadaver transplantation, and older age were significantly associated with higher risks for mortality. Conclusion. Prophylactic antifungal regimens in high-risk recipients might decrease the incidence of posttransplant fungal infections.

Survey of the provision of prophylactic dental care for horses in Great Britain and Ireland between 1999 and 2002.

Science.gov (United States)

Dixon, P M; Andrew, R; Brannon, H; Burgess, R; Gibson, A; Little, J C; Orange, B; Ross, L; Rudolph, T; Shaw, D J

2004-11-27

A survey of 854 horse owners, trainers and equestrian managers in 10 regions of Great Britain and Ireland showed that 83 per cent provided their horses with routine prophylactic dental care at fixed intervals, including 49 per cent at intervals of 12 months and 30 per cent at intervals of six months; a further 10 per cent provided it only when they felt it was required and 7 per cent did not provide it at all. Overall, 44 per cent of the owners had their horse's wolf teeth (first premolar) extracted routinely; when prophylactic dentistry was provided, it was carried out solely by equine dental technicians (EDTS) for 53 per cent of owners, solely by veterinarians for 35 per cent, by both EDTS or veterinarians for 10 per cent of owners and by other than veterinarians or EDTS for 1 per cent. There was confusion among some horse owners concerning the qualifications of the EDTS, because no recognised British qualification was available until towards the end of this survey in 2001. Several reasons were cited by owners for choosing between veterinarians and EDTS including their perceived qualifications, personal recommendations, costs, the availability of a wide range of dental equipment and sedation, and the time and effort devoted to the procedures.

Instructional Partnerships: A Pathway to Leadership

Science.gov (United States)

Moreillon, Judi, Ed.; Ballard, Susan, Ed.

2013-01-01

In this Best of "Knowledge Quest" monograph, the editors have collected seminal articles to support pre-service and in-service school librarians in developing and strengthening the instructional partner role. "Instructional Partnerships: A Pathway to Leadership" provides readers with background knowledge, research-based…

The role of ethnicity in clinical psychopathology and care pathways of adults with intellectual disabilities.

LENUS (Irish Health Repository)

Tsakanikos, Elias

2011-04-27

The objective of this study was to explore whether people with intellectual disability from ethnic minority groups have higher rates of mental health problems and access different care pathways than their White counterparts. Clinical and socio-demographic data were collected for 806 consecutive new referrals to a specialist mental health service for people with intellectual disabilities in South London. Referrals were grouped according to their ethnic origin. The analyses showed that there was an over-representation of referrals from ethnic minority groups with diagnoses of schizophrenia spectrum disorder. In addition, Black participants were more likely to have an autistic spectrum disorder. Referrals of ethnic minority groups were considerably younger than White referrals, and less likely to be in supported residences. The results are discussed in the context of cultural and familial factors in particular ethnic groups that may play an important role in accessing and using mental health services.

Effect of prophylactic trochanteric epiphyseodesis in older children with Perthes' disease.

Science.gov (United States)

Shah, Hitesh; Siddesh, Nandi D; Joseph, Benjamin; Nair, Sreekumaran N

2009-12-01

To evaluate the effect of prophylactic epiphyseodesis of the greater trochanter in Perthes' disease, 62 children with unilateral Perthes' disease who underwent trochanteric epiphyseodesis combined with varus osteotomy of the femur during the active stage of the disease (mean age at surgery: 8.4 y) and 20 controls were followed up until skeletal maturity. On radiographs taken at skeletal maturity, the articulo-trochanteric distance, the center-trochanteric distance, the length of the abductor lever arm, the neck-shaft angle, the radius of the femoral head, and the Reimer's migration index of normal and affected hips were measured. The shape of the femoral head was assessed according to the criteria of Mose. The range of hip motion, the strength of hip abduction, and limb lengths were measured and the Trendelenburg sign was elicited. The mean values of articulo-trochanteric distance and center-trochanteric distance were greater and the frequency of a positive Trendelenburg sign was less in children who had undergone trochanteric epiphyseodesis than in children who had no surgery (P<0.01). Trochanteric epiphyseodesis achieved optimal trochanteric growth arrest in 60% of operated children; the procedure was not effective in 30%, and in 10% of children there was overcorrection. Logistic regression analysis showed that the size of the femoral head at healing and the age at surgery were variables that significantly influenced the effectiveness of trochanteric growth arrest. At skeletal maturity, the mean shortening of the affected limb in operated children was 0.44 cm (SD 0.68 cm), whereas that of non-operated children was 0.86 cm (SD 0.78 cm) (P<0.05). The range of motion of the hip was excellent and there were no significant differences in the range of motion among children with optimal correction, under-correction, and overcorrection. A probability curve plotted on the basis of a logistic regression model suggests that effective trochanteric arrest may be achieved in a

Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia: radiation effects and methotrexate leukoencephalopathy

International Nuclear Information System (INIS)

Shalen, P.R.; Ostrow, P.T.; Glass, P.J.

1981-01-01

The authors report a case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice

[Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

Science.gov (United States)

Bao, X H; Li, H X; Tao, J; Li, X M; Yang, Y N; Ma, Y T; Chen, B D

2016-05-24

To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 μmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all PS1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all PS1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all PS1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and

The mitogen-activated protein kinase (MAPK pathway: role in immune evasion by trypanosomatids

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Mercedes Carolina Soares-Silva

2016-02-01

Full Text Available Leishmania spp and Trypanosoma cruzi are the causative agents of leishmaniasis and Chagas' disease, respectively, two neglected tropical diseases that affect about 25 million people worldwide. These parasites belong to the family Trypanosomatidae and are both obligate intracellular parasites that manipulate host signaling pathways to establish the infection, and also subvert the host innate immune system. Mitogen-activated protein kinases (MAPKs are serine and threonine protein kinases, highly conserved in eukaryotes, and are involved in signal transduction pathways that are related to modulation of physiological and pathophysiological cell responses. This mini-review highlights the current knowledge about the mechanisms that Leishmania spp and T. cruzi have evolved to target host MAPK signaling pathway, highjack immune response, and in this manner, promote parasite maintenance in the host.

Effects of routine prophylactic vaccination or administration of aluminum adjuvant alone on allergen-specific serum IgE and IgG responses in allergic dogs.

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Tater, Kathy C; Jackson, Hilary A; Paps, Judy; Hammerberg, Bruce

2005-09-01

To determine the acute corn-specific serum IgE and IgG, total serum IgE, and clinical responses to s.c. administration of prophylactic vaccines and aluminum adjuvant in corn-allergic dogs. 20 allergic and 8 nonallergic dogs. 17 corn-allergic dogs were vaccinated. Eight clinically normal dogs also were vaccinated as a control group. Serum corn-specific IgE, corn-specific IgG, and total IgE concentrations were measured in each dog before vaccination and 1 and 3 weeks after vaccination by use of an ELISA. The corn-allergic dogs also had serum immunoglobulin concentrations measured at 8 and 9 weeks after vaccination. Twenty allergic dogs received a s.c. injection of aluminum adjuvant, and serum immunoglobulin concentrations were measured in each dog 1, 2, 3, 4, and 8 weeks after injection. The allergic dogs were examined during the 8 weeks after aluminum administration for clinical signs of allergic disease. The allergic dogs had significant increases in serum corn-specific IgE and IgG concentrations 1 and 3 weeks after vaccination but not 8 or 9 weeks after vaccination. Control dogs did not have a significant change in serum immunoglobulin concentrations after vaccination. After injection of aluminum adjuvant, the allergic dogs did not have a significant change in serum immunoglobulin concentrations or clinical signs. Allergen-specific IgE and IgG concentrations increase after prophylactic vaccination in allergic dogs but not in clinically normal dogs. Prophylactic vaccination of dogs with food allergies may affect results of serologic allergen-specific immunoglobulin testing performed within 8 weeks after vaccination.

Differential signal pathway activation and 5-HT function: the role of gut enterochromaffin cells as oxygen sensors.

Science.gov (United States)

Haugen, Martin; Dammen, Rikard; Svejda, Bernhard; Gustafsson, Bjorn I; Pfragner, Roswitha; Modlin, Irvin; Kidd, Mark

2012-11-15

The chemomechanosensory function of the gut enterochromaffin (EC) cell enables it to respond to dietary agents and mechanical stretch. We hypothesized that the EC cell, which also sensed alterations in luminal or mucosal oxygen level, was physiologically sensitive to fluctuations in O(2). Given that low oxygen levels induce 5-HT production and secretion through a hypoxia inducible factor 1α (HIF-1α)-dependent pathway, we also hypothesized that increasing O(2) would reduce 5-HT production and secretion. Isolated normal EC cells as well as the well-characterized EC cell model KRJ-I were used to examine HIF signaling (luciferase-assays), hypoxia transcriptional response element (HRE)-mediated transcription (PCR), signaling pathways (Western blot), and 5-HT release (ELISA) during exposure to different oxygen levels. Normal EC cells and KRJ-I cells express HIF-1α, and transient transfection with Renilla luciferase under HRE control identified a hypoxia-mediated pathway in these cells. PCR confirmed activation of HIF-downstream targets, GLUT1, IGF2, and VEGF under reduced O(2) levels (0.5%). Reducing O(2) also elevated 5-HT secretion (2-3.2-fold) as well as protein levels of HIF-1α (1.7-3-fold). Increasing O(2) to 100% inhibited HRE-mediated signaling, transcription, reduced 5-HT secretion, and significantly lowered HIF-1α levels (∼75% of control). NF-κB signaling was also elevated during hypoxia (1.2-1.6-fold), but no significant changes were noted in PKA/cAMP. We concluded that gut EC cells are oxygen responsive, and alterations in O(2) levels differentially activate HIF-1α and tryptophan hydroxylase 1, as well as NF-κB signaling. This results in alterations in 5-HT production and secretion and identifies that the chemomechanosensory role of EC cells extends to oxygen sensing.