A Comparative Study on the Phenotypic Versus Molecular Identification of Clinical Dermatophytes

Dermatophytosis is the superficial infection of keratinized tissue like skin, hair, and nails, in humans and animals, by a group of closely related fungi known as dermatophytes. Phenotypic identification of dermatophytes, especially through classical methods can be difficult and uncertain at times, especially when differentiating species with overlapping characteristics. Alternative identification methods based on amplification and sequence analysis of the highly polymorphic internal transcribed spacer (ITS) sequences flanking the 5.8S ribosomal RNA gene has proven to be quite sensitive and reliable. The objective of our study was to compare the phenotypic and the ITS sequencing-based methods for the identification of clinically isolated dermatophyte specimens from Puducherry, India. A total of 13 clinical samples from 39 suspected cases were found positive for dermatophytes using KOH/DMSO preparations. Specimens were subsequently cultured in Sabouraud dextrose agar (SDA) supplemented with chloramphenicol, gentamicin, and cycloheximide. Dermatophytes were identified based on culture characteristics and microscopic examination in lactophenol cotton blue preparations. ITS sequencing was additionally performed after PCR amplification for species identification. Identification based on phenotype through microscopy and culture methods confirmed infections with Trichophyton mentagrophytes (n = 11), T. rubrum (n = 1), and Microsporum gypseum (n = 1). The strains were confirmed by ITS sequencing without any discrepancy with phenotypic identification. Identification of common dermatophytes based on phenotypic characteristics may be used as a reliable method of diagnosis where sophisticated methods like ITS sequencing and PCR are unavailable

Specific sequence determinants of miR-15/107 microRNA gene group targets

MicroRNAs (miRNAs) target mRNAs in human cells via complex mechanisms that are still incompletely understood. Using anti-Argonaute (anti-AGO) antibody co-immunoprecipitation, followed by microarray analyses and downstream bioinformatics, ‘RIP-Chip’ experiments enable direct analyses of miRNA targets. RIP-Chip studies (and parallel assessments of total input mRNA) were performed in cultured H4 cells after transfection with miRNAs corresponding to the miR-15/107 gene group (miR-103, miR-107, miR-16 and miR-195), and five control miRNAs. Three biological replicates were run for each condition with a total of 54 separate human Affymetrix Human Gene 1.0 ST array replicates. Computational analyses queried for determinants of miRNA:mRNA binding. The analyses support four major findings: (i) RIP-Chip studies correlated with total input mRNA profiling provides more comprehensive information than using either RIP-Chip or total mRNA profiling alone after miRNA transfections; (ii) new data confirm that miR-107 paralogs target coding sequence (CDS) of mRNA; (iii) biochemical and computational studies indicate that the 3′ portion of miRNAs plays a role in guiding miR-103/7 to the CDS of targets; and (iv) there are major sequence-specific targeting differences between miRNAs in terms of CDS versus 3′-untranslated region targeting, and stable AGO association versus mRNA knockdown. Future studies should take this important miRNA-to-miRNA variability into account

Post-transcriptional gene regulation: From genome-wide studies to principles

Post-transcriptional regulation of gene expression plays important roles in diverse cellular processes such as development, metabolism and cancer progression. Whereas many classical studies explored the mechanistics and physiological impact on specific mRNA substrates, the recent development of genome-wide analysis tools enables the study of post-transcriptional gene regulation on a global scale. Importantly, these studies revealed distinct programs of RNA regulation, suggesting a complex and versatile post-transcriptional regulatory network. This network is controlled by specific RNA-binding proteins and/or non-coding RNAs, which bind to specific sequence or structural elements in the RNAs and thereby regulate subsets of mRNAs that partly encode functionally related proteins. It will be a future challenge to link the spectra of targets for RNA-binding proteins to post-transcriptional regulatory programs and to reveal its physiological implications

Involvement of microRNAs in physiological and pathological processes in the lung

To date, at least 900 different microRNA (miRNA) genes have been discovered in the human genome. These short, single-stranded RNA molecules originate from larger precursor molecules that fold to produce hairpin structures, which are subsequently processed by ribonucleases Drosha/Pasha and Dicer to form mature miRNAs. MiRNAs play role in the posttranscriptional regulation of about one third of human genes, mainly via degradation of target mRNAs. Whereas the target mRNAs are often involved in the regulation of diverse physiological processes ranging from developmental timing to apoptosis, miRNAs have a strong potential to regulate fundamental biological processes also in the lung compartment. However, the knowledge of the role of miRNAs in physiological and pathological conditions in the lung is still limited. This review, therefore, summarizes current knowledge of the mechanism, function of miRNAs and their contribution to lung development and homeostasis. Besides the involvement of miRNAs in pulmonary physiological conditions, there is evidence that abnormal miRNA expression may lead to pathological processes and development of various pulmonary diseases. Next, the review describes current state-of-art on the miRNA expression profiles in smoking-related diseases including lung cancerogenesis, in immune system mediated pulmonary diseases and fibrotic processes in the lung. From the current research it is evident that miRNAs may play role in the posttranscriptional regulation of key genes in human pulmonary diseases. Further studies are, therefore, necessary to explore miRNA expression profiles and their association with target mRNAs in human pulmonary diseases

The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease.

The miR-17/92 cluster is among the best-studied microRNA clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster\u27s involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Elizabethkingia meningoseptica bacteremia in immunocompromised hosts: The first case series from India

Background: Although Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) infections in immunocompromised hosts have been recognised, clinical data detailing these infections remain limited, especially from India. Antimicrobial susceptibility data on E. meningoseptica remain very limited, with no established breakpoints by Clinical and Laboratory Standards Institute (CLSI). The organism is usually multidrug resistant to antibiotics usually prescribed for treating Gram-negative bacterial infections, a serious challenge to the patient and the treating clinicians. Materials and Methods: The analysis was done in a tertiary care oncology and stem cell transplant center. Susceptibility testing and identification of E. meningoseptica was done using Vitek auto analyzer. Records of immunocompromised patients with E. meningoseptica bacteremia were analysed from January 2009 to March 2012. Results: A total of 29 E. meningoseptica bacteremia cases were documented between 2009 and 2012. Eleven patients were immunocompromised. Three were post stem cell transplant and one was post cord blood transplant. The mean age of the patients was 48.4 years. Mean Charlson′s comorbidity index was 5.7. Four had solid organ malignancies, five had hematological malignancies, and two had lymphoreticular malignancy. Eight patients had received chemotherapy. Mean Apache II score was 18. Mean Pitts score for bacteremia was 4.7. Two were neutropenic (one post SCT, one MDS post chemo) with a mean white blood cell (WBC) count of 450/mm 3 . Ten had a line at the time of bacteremia. Mean duration of the line prior to bacteremia was 8 days. Eight had line-related bacteremia. Three had pneumonia with secondary bacteremia. All received combination therapy with two or more antibiotics which included cotrimoxazole, rifampicin, piperacillin-tazobactam, tigecycline, or cefepime-tazobactam. All the isolates showed in vitro resistance to ciprofloxacin. Five patients died, but a multivariate analysis was not done to calculate the attributable mortality. Conclusion: In our study, central line was the commonest risk factor for E. meningosepticum bacteremia, although a multivariate analysis was not done. There has not been much of a change in the susceptibility pattern of these organisms over 3 years, with good susceptibility to piperacillin-tazobactam and cotrimoxazole. Even though uncommon, E. meningoseptica is an important pathogen, especially in immunocompromised hosts with indwelling devices

AN EMPIRICAL SURVEY ON HAPPINESS AND HEALTH AMONG WORK FROM HOME EMPLOYEES BELONGING TO IT SECTOR

Many individuals and businesses were affected by the Corona virus (COVID-19) outbreak that occurred in early 2020. Work-from-home (WFH) policies have been implemented by a number of firms as a way of adapting to these changes. The literature on the effects of WFH on health issues, on the other hand, is completely divided. Work–life balance, happiness, and work stress were all examined in this study as potential predictors of job satisfaction while WFH. COVID-19 was also examined as a factor. This research examines how IT professionals felt about WFH or work from office (WFO) during the COVID-19 epidemic. It also uses individual fixed-effects models to look at how workers' subjective health varies between working at home and working in the office. As a result of the findings in this paper, governments and business leaders may reevaluate the benefits of telecommuting. During the COVID-19 pandemic, communication, organization environment, organizational policies, work satisfaction, and psychological aspects were shown to have a substantial impact on the psychological health of IT personnel