Amplified fragment length polymorphism of clinical and environmental Vibrio cholerae from a freshwater environment in a cholera-endemic area, India

<p>Abstract</p> <p>Background</p> <p>The region around Chandigarh in India has witnessed a resurgence of cholera. However, isolation of <it>V. cholerae </it>O1 from the environment is infrequent. Therefore, to study whether environmental nonO1-nonO139 isolates, which are native to the aquatic ecosystem, act as precursors for pathogenic O1 strains, their virulence potential and evolutionary relatedness was checked.</p> <p>Methods</p> <p><it>V. cholerae </it>was isolated from clinical cases of cholera and from water and plankton samples collected from freshwater bodies and cholera-affected areas. PCR analysis for the <it>ctxA, ctxB, tcpA, toxT </it>and <it>toxR </it>genes and AFLP with six primer combinations was performed on 52 isolates (13 clinical, 34 environmental and 5 reference strains).</p> <p>Results</p> <p>All clinical and 3 environmental isolates belonged to serogroup O1 and remaining 31 environmental <it>V. cholerae </it>were nonO1-nonO139. Serogroup O1 isolates were <it>ctxA, tcpA </it>(ElTor), <it>ctxB </it>(Classical), <it>toxR </it>and <it>toxT </it>positive. NonO1-nonO139 isolates possessed <it>toxR</it>, but lacked <it>ctxA </it>and <it>ctxB</it>; only one isolate was positive for <it>toxT </it>and <it>tcpA</it>. Using AFLP, 2.08% of the <it>V. cholerae </it>genome was interrogated. Dendrogram analysis showed one large heterogeneous clade (n = 41), with two compact and distinct subclades (1a and 1b), and six small mono-phyletic groups. Although <it>V. cholerae </it>O1 isolates formed a distinct compact subclade, they were not clonal. A clinical O1 strain clustered with the nonO1-nonO139 isolates; one strain exhibited 70% similarity to the Classical control strain, and all O1 strains possessed an ElTor variant-specific fragment identified with primer ECMT. Few nonO1-nonO139 isolates from widely separated geographical locations intermingled together. Three environmental O1 isolates exhibited similar profiles to clinical O1 isolates.</p> <p>Conclusion</p> <p>In a unique study from freshwater environs of a cholera-endemic area in India over a narrow time frame, environmental <it>V. cholerae </it>population was found to be highly heterogeneous, diverse and devoid of major virulence genes. O1 and nonO1-nonO139 isolates showed distinct lineages. Clinical isolates were not clonal but were closely related, indicating accumulation of genetic differences over a short time span. Though, environment plays an important role in the spread of cholera, the possibility of an origin of pathogenic O1 strains from environmental nonO1-nonO139 strains seems to be remote in our region.</p

Vitrectomy in Diabetic Retinopathy

Diabetic vitrectomy is a complicated vitreoretinal surgery due to the complex interaction of various factors. Indications of vitrectomy in diabetes patients would comprise of non-resolving vitreous haemorrhage, taut posterior hyaloid causing vitreo-papillary traction, vitreomacular traction, non-resolving macular edema due to epiretinal membrane, posterior pole tractional retinal detachment or combined retinal detachment. Pre-operative systemic evaluation, a thorough clinical evaluation with ancillary investigations like ultrasound and optical coherence tomography are important for planning the surgery. In this chapter, we would be discussing the basic principles of PVD induction, surgical steps and techniques involved in diabetic vitrectomy. Complications associated can be intraoperative or post-operative. Intra-operative complications would include corneal edema, cataract, bleeding and iatrogenic breaks. Post-operative complications can be divided into early and late, which include vitreous cavity bleeding, raised intraocular pressure, reproliferation, epiretinal membrane, cataract, glaucoma and hypotony

An overview of vaccine development for COVID-19

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date

Impact of IRS: Four-years of entomological surveillance of the Indian Visceral Leishmaniases elimination programme

BACKGROUND In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016. METHODS Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS. RESULTS Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019. CONCLUSION Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

Metal-Ylide Complexes: Mercury(II), Cadmium(II) & Palladium(II) Complexes of Ambidentate Sulphonium Ylides

1046-104