Inhibition of HCV 3a core gene through Silymarin and its fractions

Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost. In the present study Silybum marianum (Milk thistle) seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid. Our results demonstrated that Silymarin (SM) dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC), column chromatography and HPLC. Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2) inhibit HCV 3a core expression or function in liver cells Our results suggest SM and its fractions (S1 and S2) inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection

Latanoprost treatment for open angle glaucoma. The United Kingdom Glaucoma Treatment Study: a multicentre, randomised, placebo-controlled clinical trial

BACKGROUND: Treatment of open-angle glaucoma (OAG) aims to prevent vision loss by lowering intraocular pressure (IOP), yet there has been no previous placebo-controlled medical treatment trial assessing vision function preservation. Observation periods in previous (unmasked) trials assessing visual function have typically been at least 5 years. The aim of this study was to assess vision preservation by latanoprost treatment compared to placebo. METHODS In this randomised, triple-masked, placebo-controlled trial, patients with newly-diagnosed OAG were enrolled at 10 UK centres (tertiary referral centres, teaching hospitals, and district general hospitals) between Feb 2007 and Mar 2010. Eligible patients were randomly allocated (1:1) to receive either latanoprost 0·005% or placebo eye drops, provided in identical bottles, once daily to both eyes. Randomization was in permuted blocks stratified by participating centre. The primary hypothesis was that latanoprost treatment reduces incident visual field (VF) deterioration, compared with placebo, by 50% over 2 years. The primary outcome was VF deterioration: 3 locations in the Pattern Deviation Glaucoma Change Probability maps worse than baseline in 2 consecutive VFs, present in 2 consecutive VF pairs. The primary analysis was VF survival in the intention-to-treat population. The trial was terminated in July 2011 on the recommendation of the independent data monitoring committee following an interim analysis. Trial registration number: ISRCTN96423140. FINDINGS: 516 patients were randomised and data on all subjects with post-allocation data (461) were analysed. 18 serious adverse events were reported, none attributable to the study drug. Baseline mean (SD) IOP was 19·6 (4·6) mmHg and 20·1 (4·8) mmHg, and IOP reduction at 24 months 3·8 (4·0) mmHg and 0·9 (3·8) mmHg, in the latanoprost and placebo groups, respectively. Incident VF deterioration (95% CI) by 24 months was 15·0% (10·8, 20·0) in the latanoprost group and 24·8% (19·5, 30·7) in the placebo group (P=0·007). VF survival was significantly longer in the latanoprost group: at 24 months, adjusted hazard ratio (HR) 0·44 (0·28, 0·69) (P=0·0003). The difference between treatment groups was evident after only 12 months, HR 0·47 (0·23, 0·95) (P=0·035). INTERPRETATION: This is the first placebo-controlled trial to demonstrate VF preservation with an IOP-lowering agent in OAG. The study design enabled a relatively short observation period. FUNDING: Pfizer Inc.; UK National Institute for Health Research Biomedical Research Centre

A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation

Background: The benefits to health of a physically active lifestyle are well established and there is evidence that a sedentary lifestyle plays a significant role in the onset and progression of chronic disease. Despite a recognised need for effective public health interventions encouraging sedentary people with a medical condition to become more active, there are few rigorous evaluations of their effectiveness. Following NICE guidance, the Welsh national exercise referral scheme was implemented within the context of a pragmatic randomised controlled trial. Methods/Design: The randomised controlled trial, with nested economic and process evaluations, recruited 2,104 inactive men and women aged 16+ with coronary heart disease (CHD) risk factors and/or mild to moderate depression, anxiety or stress. Participants were recruited from 12 local health boards in Wales and referred directly by health professionals working in a range of health care settings. Consenting participants were randomised to either a 16 week tailored exercise programme run by qualified exercise professionals at community sports centres (intervention), or received an information booklet on physical activity (control). A range of validated measures assessing physical activity, mental health, psycho-social processes and health economics were administered at 6 and 12 months, with the primary 12 month outcome measure being 7 day Physical Activity Recall. The process evaluation explored factors determining the effectiveness or otherwise of the scheme, whilst the economic evaluation determined the relative cost-effectiveness of the scheme in terms of public spending. Discussion: Evaluation of such a large scale national public health intervention presents methodological challenges in terms of trial design and implementation. This study was facilitated by early collaboration with social research and policy colleagues to develop a rigorous design which included an innovative approach to patient referral and trial recruitment, a comprehensive process evaluation examining intervention delivery and an integrated economic evaluation. This will allow a unique insight into the feasibility, effectiveness and cost effectiveness of a national exercise referral scheme for participants with CHD risk factors or mild to moderate anxiety, depression, or stress and provides a potential model for future policy evaluations. Trial registration: Current Controlled Trials ISRCTN4768044

ICAR: endoscopic skull‐base surgery

n/

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS