96 research outputs found

    Small molecule activators of the Trk receptors for neuroprotection

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    The neurotophin signaling network is critical to the development and survival of many neuronal populations. Especially sensitive to imbalances in the neurotrophin system, cholinergic neurons in the basal forebrain are progressively lost in Alzheimer's disease. Therapeutic use of neurotrophins to prevent this loss is hampered, however, by a number of pharmacological challenges. These include a lack of transport across the blood-brain barrier, rapid degradation in the circulation, and difficulty in production. In this review we discuss the evidence supporting the neurotrophin system's role in preventing neurodegeneration and survey some of the pharmacological strategies being pursued to develop effective therapeutics targeting neurotrophin function

    A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions.

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    BACKGROUND: Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world's population need a prosthesis or orthosis. OBJECTIVE: The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. METHODS: Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. RESULTS: A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. CONCLUSIONS: At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness

    Cerebral ischemic damage in diabetes: an inflammatory perspective

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    Insulin mimetics

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    Prevalence and Genetic Diversity of Grapevine Virus D in Tunisia

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    The prevalence and the genetic diversity of grapevine virus D (GVD) isolates from rootstocks, wine and table grape varieties grown in Tunisia were studied. RT-PCR assays performed on the coat protein gene (CP) showed the presence of GVD in 31.5% of the 403 samples tested. The highest rate of infection was found in table grapes (56.5%), followed by autochthonous table grapes (24.1%), wine grapes (20.8%) and rootstocks (12.5%).  Sequences and phylogenetic analyses of the partial CP genes of 14 GVD isolates showed nucleotide identities that ranged from 84% to 99%. The  Tunisian GVD-isolates segregated in 3 phylogenetic groups together with international isolates reported in GenBank. The present study extends our  knowledge of the presence of GVD in Tunisian vines and on its genetic diversity, which is useful for developing broad-spectrum molecular  diagnostics (RT-PCR) capable of detecting the different isolates infecting vines

    CO and VOC as indicators of indoor air quality in underground parking facilities

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    The provision of underground parking facilities (UPFs) has become a necessity particularly in densely populated urban areas and business districts. Indoor air quality (IAQ) in such facilities is of great concern due to vehicle-induced emissions. This paper presents an IAQ as sessment at six representative UPFs in Beirut using carbon monoxide and volatile organic compounds as IAQ indicators. For this purpose, concentrations of both pollutants were measured at different time intervals throughout the day. Vehicular emission factors (EFs) were estimated using the EMFAC7F1.1 model. A transient mass balance model was then applied to construct concentration profiles. The ventilation rates required to maintain pollutant concentrations within acceptable standards were estimated under maximum UPF occupancy, and a sensitivity analysis was conducted to evaluate the effect of changes in EMFAC7F1.1 input parameters on EFs and ventilation rates

    Intraoperative low-field MR-guided frameless stereotactic biopsy for intracerebral lesions

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    BACKGROUND: To present our intraoperative low-field magnetic resonance imaging (ioMRI) technique for stereotactic brain biopsy in various intracerebral lesions. METHOD: Seventy-eight consecutive patients underwent stereotactic biopsies with the PoleStar N-20/N-30 ioMRI system and data were evaluated retrospectively. Biopsy technique included ioMRI before surgery, followed by insertion of the biopsy cannula in the lesion, and ioMRI before and after biopsy. Statistical analysis was performed to compare subgroups using Excel and SPSS statistic software. RESULTS: In all patients, stereotactic biopsy was possible, with a mean intraoperative surgery time of 86.2 ± 28.6 min and a mean hospital stay of 11.6 ± 4.6 days. In 97.4 % (n = 76), histology was conclusive, representing 58 brain tumors and 18 other pathologies. Five patients were biopsied previously without conclusive diagnosis, and all biopsies were conclusive this time. Mean cross-sectional lesion size in MRI T1 with contrast (n = 64) was 6.9 ± 5.7 cm(2), and in lesions without T1 contrast enhancement (n = 14), T2 mean cross-sectional lesion size was 5.5 ± 3.9 cm(2). Mean distance from the cortex surface to the lesion was 3.4 ± 1.2 cm. One patient suffered from a postoperative wound dehiscence; neither clinically or radiologically significant hemorrhage after surgery, nor intraoperative complications occurred. CONCLUSIONS: Low-field ioMR-guided frameless stereotactic biopsy accurately diagnosed different intracerebral lesions without major complications for the patients, and within an acceptable surgery time and hospital stay. In repeated non-conclusive biopsies in particular, low-field ioMRI offers a technique for arriving at a diagnosis

    The disparity in long-term survival after a first stroke in patients with and without diabetes persists : the Northern Sweden MONICA Study

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    Background: Diabetes is an established risk factor for stroke. Compared to nondiabetic patients, diabetic patients also have an increased risk of new vascular events and death after stroke. We analyzed how differences in long-term survival between diabetic and nondiabetic stroke patients have changed over time, and if differences varied with respect to sex and age. Methods: This population-based study included 12,375 first-ever stroke patients, 25-74 years old, who were registered in the Northern Sweden MONICA Stroke Registry 1985-2005. Uniform diagnostic criteria for stroke case ascertainment were used throughout the study period. The diagnosis of diabetes was based on medical records or diabetes diagnosed during the acute stroke event. Patients were separated into four cohorts according to year of stroke and followed for survival until August 30, 2008. Results: The diabetes prevalence at stroke onset was 21%, similar in men and women, and remained stable throughout the study period. The diabetic patients were an average of 2 years older, more often nonsmokers and more likely to have antihypertensive treatment, antithrombotics, atrial fibrillation, and a history of myocardial infarction or transient ischemic attack than the nondiabetic patients. The total follow-up time was 86,086 patient-years during which a total of 1,930 (75.7%) of the diabetic patients and 5,744 (58.5%) of the nondiabetic patients died (p < 0.001). Median survival was 60 months (95% CI: 57-64) in diabetic patients and 117 months (113-120) in the nondiabetic patients. Survival improved significantly in both groups (p < 0.001). A Cox regression, adjusting for possible confounders (age, sex, antihypertensive medication, antithrombotics or other thrombolytic agents, history of myocardial infarction, type of stroke, diabetes, cohort and the diabetes-by-sex, diabetes-by-age and diabetes-by-cohort interactions), showed a hazard ratio of 1.67 (1.58-1.76) comparing survival in diabetic versus nondiabetic patients. The reduced survival in diabetic stroke patients was more pronounced in women (p = 0.02) and younger patients (p < 0.001). There was a tendency that the difference in survival decreased between the earlier cohorts and the 2000-2005 cohort, but the test for interaction did not reach statistical significance (p = 0.08). Conclusion: Long-term survival after a first stroke has improved in both diabetic and nondiabetic patients. Survival is markedly lower in diabetics, especially in women and younger patients, and the disparity persisted over 24 years. Decreasing the disparity in stroke survival is a challenge for stroke and diabetes care. New treatment methods in combination with intense secondary prevention in diabetic patients, especially in younger women, are needed
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