The characteristics of HIV patients who are long-term responders to nevirapine

Objective: To define Nevirapine long term responders (NLTRs) and identify the characteristics of patients who stay on the drug for long periods of time without adverse effects and maintain suppression of HIV replication without development of resistance.Methodology: Demographic and clinical data was collected for all the patients >18 years old from Department of Clinical Immunology, Royal Perth Hospital, Western Australia. All the patients included in the study received Nevirapine as part of their first regimen of anti-retroviral therapy. Data collection and analysis were divided in three groups based on their length of stay on Nevirapine; short-term, medium and long-term responders. Patients who stayed on Nevirapine continuously for more than five years were considered long-term responders (60+ months). Patients who withdraw before six months of therapy due to the drug’s side effects or any other reason are considered short-term responders (0-6 months). Patients whose length of stay on the drug is intermediate between these two groups are considered as medium responders (6-60 months). Investigation of the possible genetic influence on response to Nevirapine was made by analysis of genetic markers like HLA-B35+C4, HLA-DR1, and HLA-B14.Results: We found no difference in the frequencies of HLA-DR1 or HLA- B14 in the three groups. However, we found that HLA-B35+HLA-C4 did not occur in any of the Nevirapine long term responders (NLTRs). This was not described in previous studies. Furthermore, when a survival analysis was performed, carriage of HLA-B35+HLA-C4 identified patients who were not NLTRs.Conclusion: This study was carried out to determine whether or not factors like age, gender, baseline CD4+ count, baseline RNA, and HLA alleles would predict the length of stay on Nevirapine. Although the factors considered for the study have previously been associated with hyper-sensitivity reactions, they do not predict how long a patient would stay on the drug. However, it can be understood from the study that patients who had a combination of HLA alleles B35+HLA-C4 would not continue on Nevirapine use for a prolonged time

Fractionation of antibacterial extracts of Syzygium cumini (Myrtaceae) seeds

Antibacterial activity of Syzygium cumini seed extracts prepared in methanol and ethanol was evaluated by disc diffusion and broth dilution assays. Both extracts exerted a broad spectrum of bacteriostatic action against different gram-positive and gram-negative bacteria. Their minimum inhibitory concentration (MIC) against susceptible organisms ranged from 154-656 μg/mL. Highest total activity was registered by the ethanol extract against Staphylococcus epidermidis. Extracts were separated on TLC (thin-layer chromatography) plates, and separated components were individually tested  for their antibacterial activity. HPLC (high performance liquid chromatography) analysis indicated presence of gallic acid and quercetin in the methanolic extract

TRENDS IN IT HUMAN RESOURSES AND END-USERS INVOLVED IN IT APPLICATIONS

The Bureau of Labor Statistics projected the demand for information technology (IT) human resources to increase by 13.26 percent between 2014 and 2024. In this survey research, the IT professionals estimated a growth of 34.16 percent in IT human resources over a period of five years from the year 2016. The goal of this survey study was to try to understand the discrepancy in the estimates for IT human Resources requirements by developing a theory-driven model to evaluate the impact of growth in IT outsourcing/offshoring, cloud-computing, end-users-computing, IT applications, and usage of commercial-off-the-shelf/ERP on the need for IT human resources

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.Peer reviewe

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

In vitro antibacterial activity in seed extracts of Manilkara zapota, Anona squamosa, and Tamarindus indica

Extracts prepared from seeds of Manilkara zapota, Anona squamosa, and Tamarindus indica were screened for their antibacterial activity by disc diffusion and broth dilution methods. Acetone and methanol extracts of T. indica seeds were found active against both gram-positive and gram-negative organisms. MIC values of potent extracts against susceptible organisms ranged from 53-380 μg/mL. Methanol extract of T. indica and acetone extract of M. zapota seeds were found to be bactericidal