Molecular typing of Neisseria gonorrhoeae from hospital and community isolates by restriction fragment length polymorphism

Strains of Neisseria gonorrhoeae are generally characterized by auxotyping, serotyping, plasmid profile, antibiotic sensitivity and deoxyribonucleic acid (DNA) amplification fingerprinting. The aim of this study was to analyse the generation of restriction fragment length polymorphism (RFLP) patterns by BgIII digestion of total genomic DNA of N. gonorrhoeae isolated from the community (n =30) and the hospital (n =15) and to establish an association with serogrouping and antibiogram. The RFLP patterns produced by BgIII restriction digestion showed 7 different patterns among 30 community isolates and 9 different patterns among 15 hospital isolates. 66.7% of isolates belonged to serogroup WI. Penicillin resistance was observed in 46.7% of community isolates and 66.7% hospital isolates. However, penicillinase producing N. gonorrhoeae (PPNG) were lower in the community (6.6%) than in the hospital isolates (53.3%). PPNG strains were more often seen in serogroup WI. This is the first Indian report on RFLP genotype pattern in N. gonorrhoeae. We noted differences in RFLP genotypes of the community (RFLP types 1, 2, 3, 4, 5 and 7) and hospital strains (RFLP types 6 and 8), while no differences in the serogroup were observed. Ciprofloxacin resistance was 20.0% and 26.6% in the community and hospital isolates, respectively. Ceftriaxone emerges as the current drug of choice for an effective policy of antibiotic treatment of gonorrhoea through syndromic management in developing countries.     

Development of Ulcer Disease After Roux-en-Y Gastric Bypass, Incidence, Risk Factors, and Patient Presentation: A Systematic Review

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the gold standard in bariatric surgery. A long-term complication can be marginal ulceration (MU) at the gastrojejunostomy. The mechanism of development is unclear and symptoms vary. Management and prevention is a continuous subject of debate. The aim was to assess the incidence, mechanism, symptoms, and management of MU after LRYGB by means of a systematic review. Forty-one studies with a total of 16,987 patients were included, 787 (4.6 %) developed MU. The incidence of MU varied between 0.6 and 25 %. The position and size of the pouch, smoking, and nonsteroidal inflammatory drugs usage are associated with the formation of MU. In most cases, MU is adequately treated with proton pump inhibitors, sometimes reoperation is required. Laparoscopic approach is safe and effective.     

Optimization of Drug-Like Properties of Nonsteroidal Glucocorticoid Mimetics and Identification of a Clinical Candidate

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The N-terminal region containing the zinc finger domain of tobacco streak virus coat protein is essential for the formation of virus-like particles

Tobacco streak virus (TSV), a member of the genus Ilarvirus (family Bromoviridae), has a tripartite genome and forms quasi-isometric virions. All three viral capsids, encapsidating RNA 1, RNA 2 or RNA 3 and subgenomic RNA 4, are constituted of a single species of coat protein (CP). Formation of virus-like particles (VLPs) could be observed when the TSV CP gene was cloned and the recombinant CP (rCP) was expressed in E. coli. TSV VLPs were found to be stabilized by Zn²⁺ ions and could be disassembled in the presence of 500 mM CaCl_2. Mutational analysis corroborated previous studies that showed that an N-terminal arginine-rich motif was crucial for RNA binding; however, the results presented here demonstrate that the presence of RNA is not a prerequisite for assembly of TSV VLPs. Instead, the N-terminal region containing the zinc finger domain preceding the arginine-rich motif is essential for assembly of these VLPs.     

Requirement for TLR2 in the development of albuminuria,inflammation and fibrosis in experimental diabetic nephropathy

Inflammation and fibrosis are essential elements of diabetic nephropathy (DN). We tested the hypothesis that these elements are dependent upon Toll-like receptor 2 (TLR2) signalling by examining WT and TLR2^-/- mice in an experimental model of DN. Diabetes was induced in WT and TLR2^-/- mice by i.p. injection of streptozotocin. Kidney injury was assessed at 6, 12 and 24 weeks after induction of diabetes. Gene expression of TLR2, its endogenous ligands and downstream cytokines, chemokines and fibrogenic molecules were upregulated in kidneys from WT mice with streptozotocin diabetes. TLR2^-/- mice were protected against the development of DN, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic WT controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA) and expression of fibrogenic genes (TGF-β and fibronectin) were also evident in TLR2 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR2 activation in podocytes and tubular epithelial cells (TECs) in vitro, resulting in NF-κB activation, inflammation and TGF-β production. We conclude that TLR2 was required for the full development of inflammation, kidney damage and fibrosis in this model of DN. As TLR2 is known to be expressed by intrinsic kidney cells and as high concentration glucose stimulated podocytes and TECs in vitro to express TLR2 and TLR2 ligands, pro-inflammatory and pro-fibrotic cytokines in a TLR2 dependent manner in the present study, it appears likely that TLR2 signalling in intrinsic kidney cells contributes to the pathogenesis of diabetic nephropathy.     

Predictors of Major Bleeding Among Working-Age Adults with Atrial Fibrillation: Evaluating the Effects of Potential Drug-drug Interactions and Switching from Warfarin to Non-vitamin K Oral Anticoagulants

Purpose

This study aims to evaluate the associations between switching from warfarin to non-vitamin K oral anticoagulants (NOACs), exposure to potential drug-drug interactions (DDIs), and major bleeding events in working-age adults with atrial fibrillation (AF).

Methods

We conducted a retrospective cohort study using the claims database of commercially insured working-age adults with AF from 2010 to 2015. Switchers were defined as patients who switched from warfarin to NOAC; non-switchers were defined as those who remained on warfarin. We developed novel methods to calculate the number and proportion of days with potential DDIs with NOAC/warfarin. Multivariate logistic regressions were utilized to evaluate the associations between switching to NOACs, exposure to potential DDIs, and major bleeding events.

Results

Among a total of 4126 patients with AF, we found a significantly lower number of potential DDIs and the average proportion of days with potential DDIs in switchers than non-switchers. The number of potential DDIs (AOR 1.14, 95% CI 1.02–1.27) and the HAS-BLED score (AOR 1.64, 95% CI 1.48–1.82) were significantly and positively associated with the likelihood of a major bleeding event. The proportion of days with potential DDIs was also significantly and positively associated with risk for bleeding (AOR 1.42, 95% CI 1.03, 1.96). We did not find significant associations between switching to NOACs and major bleeding events.

Conclusions

The number and duration of potential DDIs and patients’ comorbidity burden are important factors to consider in the management of bleeding risk in working-age AF adults who take oral anticoagulants.