Detection, quantification and genotype distribution of HCV patients in Lahore, Pakistan by real-time PCR

Background: Hepatitis C virus (HCV) is considered as \u201cViral Time Bomb\u201d suggested by the World Health Organization and if it is not treated timely, it will lead towards cirrhosis and hepatocellular carcinoma (HCC). Objective: The purpose of the present research is to study possible risk factors, frequent genotypes of HCV and its association with different age groups. Methods: Suspected blood samples from HCV patients were collected from different hospitals of Lahore, Pakistan. Out of 1000 HCV suspected samples, 920 samples were found HCV positive detected by Anti-HCV ELISA, CobasR. kit. The quantification of HCV load was determined by HCV quantification kit and LINEAR ARRAY KIT (Roche) was used for genotype determination by Real-Time PCR (ABI). Statistical analysis was done by using Microsoft Excel. Results: Out of 920 subjects, 77 subjects (8.4%) were false positive and they were not detected by nested PCR. Three PCR positive samples were untypeable. Genotype 3 was predominant in Lahore which was 83.5%, whereas type 1 and 2 were 5.1% and 0.7% respectively. There were also mixed genotypes detected, 1 and 3 were 0.4%, 2 and 3 were 1.41% and 3 and 4 were 0.2% only. Male were more infected of HCV in the age <40 years and females >40years. Conclusion: The major risk factor for HCV transmission is by use of unsterilized razors/blades. It is necessary to spread awareness among the general population of Pakistan about HCV transmission risk factors. Regular physical examination at least once a year is recommended, so that early detection of HCV could be done

Characterizing a regulatory axis of microRNA-200b, the RNA-binding protein quaking, and cyclin D1 in modulating tumor angiogenesis and metastasis

Angiogenesis is critical to cancer development and metastasis. However, anti-angiogenic agents have only had modest therapeutic success, partly due to an incomplete understanding of tumor endothelial cell (EC) biology. The Pecot lab previously reported that the microRNA (miR)-200 family inhibits metastasis through regulation of tumor angiogenesis, but the underlying molecular mechanisms are poorly characterized. Here, using integrated bioinformatics approaches, I identified the RNA-binding protein (RBP) quaking (QKI) as a leading miR-200b endothelial target with previously unappreciated roles in the tumor microenvironment (TME) in lung cancer. In lung cancer samples, both miR-200b suppression and QKI overexpression corresponded with tumor ECs relative to normal ECs, and QKI silencing phenocopied miR-200b-mediated inhibition of sprouting. Additionally, both cancer cell and endothelial QKI expression in patient samples significantly corresponded with poor survival and correlated with angiogenic indices. QKI supported EC function by stabilizing cyclin D1 (CCND1) mRNA to promote EC G1/S cell cycle transition and proliferation. Both nanoparticle-mediated RNA interference (RNAi) of endothelial QKI expression and palbociclib blockade of CCND1-CDK4/6 function potently inhibited metastasis in concert with significant effects on tumor vasculature. Altogether, this work demonstrates the clinical relevance and therapeutic potential of a novel, actionable miR/RBP axis in tumor angiogenesis and metastasis.Doctor of Philosoph

Conducting a diabetes mellitus prevention trial in women with GDM in Pakistan: A feasibility study

Background: Women with gestational diabetes mellitus (GDM) are at a greater risk of developing type 2 diabetes mellitus (T2DM) than women without GDM. Despite this elevated risk, few trials on the prevention of T2DM among South Asian women with GDM have been reported. Therefore, this study aimed to assess the feasibility of conducting a diabetes prevention program on women with a history of GDM to inform the development of a contextually relevant definitive trial.Methods: Using a randomized controlled trial, women with GDM (n = 180) who delivered at the study hospitals (one public and one private teaching hospital, Karachi) with fasting blood glucose levels \u3c 120 mg/dl at 6 weeks postpartum were randomized to the intervention (n = 88) or control arms (n = 92). Women in the intervention group received individualized home-based educational sessions from trained community health workers at 0, 1, 3, 6, and 9 months. In addition, they received short text messages, prerecorded messages, and printed educational material (calendars and pamphlets) for reinforcement. The intervention was centered on equipping women with knowledge, skills, and confidence to eat a healthy diet rich in fruits, vegetables, and low-fat dairy products and perform regular physical activity based on walking and household chores to reduce weight (up to 5% of their initial body weight). Women in the control arm received standard care. The feasibility outcomes of the study included screening, recruitment, and retention rates and in-depth interviews at 6 months post-intervention to explore women\u27s experiences with the intervention. Descriptive analysis and thematic analysis were performed.Results: Of the 324 women screened during the antenatal care visits and after delivery, 255 (78.7%) were contactable 6 weeks postpartum, and 180 (70.6%) were eligible and randomized to intervention (n = 88) and control (n = 92) groups. Loss to follow-up in the intervention and control arms was 22.7% (n = 20/88) and 18.5% (n = 17/92), respectively. Women expressed satisfaction with home-based counseling and follow-up visits, text message reminders, and printed material in the form of a calendar through our qualitative interviews.Conclusions: Home-based lifestyle modification intervention augmented with text messages and printed material is feasible. However, to evaluate the intervention\u27s effectiveness, a larger trial is warranted to assess its long-term impact on diabetes prevention.Trial registration: ISRCTN, ISRCTN11387113 . Registered 5 December 2017-retrospectively registered

Clade- and species-specific features of genome evolution in the Saccharomycetaceae

International audienceMany aspects of the genomes of yeast species in the family Saccharomycetaceae have been well conserved during evolution. They have similar genome sizes, genome contents, and extensive collinearity of gene order along chromosomes. Gene functions can often be inferred reliably by using information from Saccharomyces cerevisiae. Beyond this conservative picture however, there are many instances where a species or a clade diverges substantially from the S. cerevisiae paradigm-for example, by the amplification of a gene family, or by the absence of a biochemical pathway or a protein complex. Here, we review clade-specific features, focusing on genomes sequenced in our laboratory from the post-WGD genera Naumovozyma, Kazachstania and Tetrapisispora, and from the non-WGD species Torulaspora delbrueckii. Examples include the loss of the pathway for histidine synthesis in the cockroach-associated species Tetrapisispora blattae; the presence of a large telomeric GAL gene cluster in To. delbrueckii; losses of the dynein and dynactin complexes in several independent yeast lineages; fragmentation of the MAT locus and loss of the HO gene in Kazachstania africana; and the patchy phylogenetic distribution of RNAi pathway components

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.The aim of this study was to inform vaccination prioritization by modelling the impact of vaccination on elective inpatient surgery. The study found that patients aged at least 70 years needing elective surgery should be prioritized alongside other high-risk groups during early vaccination programmes. Once vaccines are rolled out to younger populations, prioritizing surgical patients is advantageous