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  • Lomholt posted an update 1 year ago

    Osteoarthritis (OA) is characterized by irreversible cartilage degradation with very limited therapeutic interventions. Drug candidates targeted at prototypic players had limited success until now and systems based approaches might be necessary. Consequently, drug evaluation platforms should consider the biological complexity looking beyond well-known contributors of OA. In this study an ex vivo model of cartilage degradation, combined with measuring releases of 27 proteins, was utilized to study 9 drug candidates. After an initial single drug evaluation step the 3 most promising compounds were selected and employed in an exhaustive combinatorial experiment. The resulting most and least promising treatment candidates were selected and validated in an independent study. This included estimation of mechanical properties via finite element modelling (FEM) and quantification of cartilage degradation as glycosaminoglycan (GAG) release. The most promising candidate showed increase of Young’s modulus, decrease of hydraulic permeability and decrease of GAG release. The least promising candidate exhibited the opposite behaviour. The study shows the potential of a novel drug evaluation platform in identifying treatments that might reduce cartilage degradation. It also demonstrates the promise of exhaustive combination experiments and a connection between chondrocyte responses at the molecular level with changes of biomechanical properties at the tissue level.Purpose of review To review the clinical evidence of the effect of aspirin as primary prevention for patients with diabetes mellitus and in healthy elderly. Recent findings Two trials were performed to study these two patient populations ASCEND showed that the use of low-dose aspirin in persons with diabetes, who did not have prior cardiovascular disease, led to a lower risk of cardiovascular events than placebo (8.5% vs 9.6%, rate ratio 0.88, 95% CI 0.79-0.97; p = 0.01). However, it showed a similar magnitude of increased risk of major bleeding among the aspirin group compared with placebo (4.1% vs 3.2%, rate ratio 1.29, 95% CI 1.09-1.52; p = 0.003). ASPREE showed that the use of low-dose aspirin in healthy elderly did not prolong disability-free survival (21.5% vs 21.2%, HR 1.01, 95% CI 0.92-1.11; p = 0.79); however, the rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs 2.8%, HR 1.38, 95% CI 1.18-1.62; p less then 0.001). Additionally, further analyses of secondarer rate of major hemorrhage.One of the roles of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) is to provide guidance on the management of patients seeking surgery for adiposity-based chronic diseases. The role of endoscopy around the time of endoscopy is an area of clinical controversy. In 2018, IFSO commissioned a task force to determine the role of endoscopy before and after surgery for the management of adiposity and adiposity-based chronic diseases. The following position statement is issued by the IFSO Endoscopy in Bariatric/Metabolic Surgery Taskforce. It has been approved by the IFSO Scientific Committee and Executive Board. This statement is based on current clinical knowledge, expert opinion, and published peer-reviewed scientific evidence. It will be reviewed regularly.Patients with obesity and diabetes have higher risk for severe complications and mortality from COVID19 infection. In addition, unexpected mortalities were reported in a small series of asymptomatic COVID19-positive patients undergoing metabolic and bariatric surgery (MBS). Several organization including IFSO and the American College of Surgeons (ACS) endorsed recommendations to suspend elective nonessential surgery including MBS during the peak period of COVID19. However, both recommendations have no clear guidelines on how to prioritize MBS patients after the peak of COVID19 cases has passed, but there remain patients with asymptomatic COVID19 in the community. We present a tiered approach to restart MBS during the COVID19 pandemic once the peak of new cases has passed or the curve of new COVID19 cases has flattened.Background Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive rise in pulmonary vascular resistance. Ambrisentan is an oral, propanoic acid based-endothelin receptor antagonist (ERA), selective for the endothelin type-A receptor, which is approved for the treatment of PAH. Idelalisib supplier The Colombia National Food and Drug Surveillance Institute regulatory criteria require demonstrating that the proposed generic product is bioequivalent to its reference-listed drug to obtain marketing approval. Objectives The purpose of this study was to test the bioequivalence, pharmacokinetics, and tolerability of ambrisentan 10 mg tablets. Methods In this open-label, randomized, oral single-dose, two-way crossover bioequivalence study, 26 Mexican adult healthy male subjects received either the generic product of ambrisentan 10 mg or the reference product Volibris® (ambrisentan) 10 mg tablets during each study period under fasting conditions. There was a 7-day washout period between each dosing. Ambrisentan ale population of this study. Trial registration COFEPRIS National Clinical Trials Registry number 183300410B0367/2018.West Nile virus neuroinvasive disease (WNVND) manifests with meningitis, encephalitis, and/or acute flaccid paralysis. It represents less than 1% of the clinical syndromes associated with West Nile virus (WNV) infection in immunocompetent patients. Immunosuppressive therapy is associated with increased risk of WNVND and worse prognosis. We present a patient with WNVND during therapy with rituximab, and a review of the literature for previous similar cases with the goal to describe the clinical spectrum of WNVND in patients treated specifically with rituximab. Our review indicates that the most common initial complaints are fever and altered mental status, brain magnetic resonance imaging often shows bilateral thalamic hyperintensities, and cerebrospinal analysis consistently reveals mild lymphocytic pleocytosis with elevated protein, positive WNV polymerase chain reaction, and negative WNV antibodies. Treatment is usually supportive care, with intravenous immunoglobulins (IVIG) plus corticosteroids and WNV-specific IVIG also used.

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