Initial Virologic Response and HIV Drug Resistance Among HIV-Infected Individuals Initiating First-line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India

Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/μL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (≥70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line AR

Fecal Microbiota in Premature Infants Prior to Necrotizing Enterocolitis

Intestinal luminal microbiota likely contribute to the etiology of necrotizing enterocolitis (NEC), a common disease in preterm infants. Microbiota development, a cascade of initial colonization events leading to the establishment of a diverse commensal microbiota, can now be studied in preterm infants using powerful molecular tools. Starting with the first stool and continuing until discharge, weekly stool specimens were collected prospectively from infants with gestational ages ≤32 completed weeks or birth weights≤1250 g. High throughput 16S rRNA sequencing was used to compare the diversity of microbiota and the prevalence of specific bacterial signatures in nine NEC infants and in nine matched controls. After removal of short and low quality reads we retained a total of 110,021 sequences. Microbiota composition differed in the matched samples collected 1 week but not <72 hours prior to NEC diagnosis. We detected a bloom (34% increase) of Proteobacteria and a decrease (32%) in Firmicutes in NEC cases between the 1 week and <72 hour samples. No significant change was identified in the controls. At both time points, molecular signatures were identified that were increased in NEC cases. One of the bacterial signatures detected more frequently in NEC cases (p<0.01) matched closest to γ-Proteobacteria. Although this sequence grouped to the well-studied Enterobacteriaceae family, it did not match any sequence in Genbank by more than 97%. Our observations suggest that abnormal patterns of microbiota and potentially a novel pathogen contribute to the etiology of NEC

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Utility of line probe assay for the early detection of multidrug-resistant pulmonary tuberculosis

Background: Despite endorsement of the line probe assay (LPA) for the diagnosis of drug-resistant pulmonary tuberculosis patients, there is limited data available on the performance of LPAs in India, especially from high burden states like Maharashtra, for the early diagnosis and detection of drug resistance, in order to initiate timely and appropriate treatment. Objective: To evaluate the utility of the line probe assay (LPA) for the early diagnosis of drug-resistant pulmonary tuberculosis as compared to the ′Gold standard′ 1% proportion method (PM). Materials and Methods: A total of 687 patients suspected of pulmonary tuberculosis were screened. One hundred samples (95 sputum and 5 BAL), positive for Acid Fast Bacilli (AFB) by Ziehl Neelson (ZN) smears, were included in the study. Digested and decontaminated specimens were subjected directly to the LPA (Genotype MTBDR@ plus assay) and were processed in parallel using the conventional culture on the Lowenstein-Jensen (LJ) medium followed by drug susceptibility testing (DST) using the PM. Results: All the 100 samples gave interpretable results on LPA with a turnaround time of 24-48 hours as opposed to six to eight weeks taken by the 1% proportion method. Sensitivity for the detection of rifampicin, isoniazid, and multidrug resistance (MDR) was 98.1, 92.1, and 95%, respectively, with a specificity of 97.8% for rifampicin and 98.33% for MDR detection. It also had the additional advantage of allowing a study of mutation patterns. Conclusions: High performance characteristics and a short turnaround time makes LPA an excellent diagnostic tool, for an early and accurate diagnosis, in a high MDR- TB-prevalent region, as reflected from our data

Knowledge, Attitude and Practice of Pharmacovigilance among Ayurveda Doctors Practicing in Wardha, Maharashtra, India: A Cross-sectional Study

Introduction: Adverse Drug Reactions (ADRs) significantly, cause morbidity and mortality worldwide. As a result, proper ADR monitoring is required. Considering the consequence of this area, the Ministry of AYUSH has introduced a Pharmacovigilance programme for Ayurveda, Siddha, Unani and Homeopathy (ASU&H) drugs. Every Ayurveda Practitioner’s (AP) immense responsibility is to detect and report ADR. Aim: To evaluate the knowledge, attitude, and practice of Pharmacovigilance among AP in Wardha, Maharashtra, India. Materials and Methods: A cross-sectional survey was conducted in a Government Hospital, Wardha, Maharashtra during March to May 2022. Total 38 Ayurveda Doctors of Wardha city having Bachelor of Ayurvadic Medicine and Surgery (BAMS), MD degree, either working in private clinics and hospitals or as medical officers were enrolled in the study. A validated questionnaire was prepared on Google form, circulated through WhatsApp to the doctors, and asked them to fill and submit it within seven days. The collected data were analysed using MS Excel 2007 and expressed in percentages (%). Results: Thirty (78.94%) male, and 08 (21.05%) female doctors possessing BAMS degrees (68.42%) and postgraduate degrees (37.57%), with practice experience between 5 to 30 years participated in the study. Present study revealed that 32 (84.21%) of the BAMS doctors from Wardha city believed that Ayurveda drugs do not cause ADRs, and only 06 (21.05%) have encountered ADRs in their practice, of which only 02 (5.26%) reported an ADR. Conclusion: The present study revealed that AP are well aware about ADR but lacking in the knowledge of its reporting. There is a strong need to organise sensitisation and awareness programmes to implement the pharmocovigilance effectively

Effect of stress on sleep quality in young adult medical students: a cross sectional study

Background: Because of demanding clinical and academic duties, medical students are at an increased risk for development of sleep disruption. Studying the relation between sleep quality and psychological stress can be useful in implementing an organized mental health program in medical colleges. The main objective is to study the prevalence and the effect of stress on sleep quality in young adult medical students.Methods: A cross sectional study to recognize the effect of stress on sleep quality among 50 medical students. The instruments used for data collection were a self-report Pittsburg Sleep Quality Index (PSQI) and the General Health Questionnaire (GHQ).Results: Results of present study showed that 58% of subjects were poor sleepers. Furthermore, there was a significant correlation between general health status and sleep quality of students (r = 0.5118, p = 0.0001).Conclusions: A considerable proportion of medical students are affected by poor sleep quality. Sleep disruption acts as a barrier for students’ performance in examinations. So, it is important to implement health promotion and educational programs for them

Tissue IgG4-Positive Plasma Cells in Inflammatory Bowel Disease: A Study of 88 Treatment-Naive Biopsies of Inflammatory Bowel Disease

The distinction of Crohn's disease from ulcerative colitis is based on clinical, endoscopic, radiological, and histological findings, a paradigm that remains unchanged despite the advent of new understanding of the immunological and genetic basis of inflammatory bowel disease. There is a strong correlation between inflammatory bowel disease, predominantly ulcerative colitis, and autoimmune pancreatitis. We hypothesized that colonic biopsies from patients with inflammatory bowel disease would demonstrate increased numbers of IgG4-positive plasma cells and that this elevation might be restricted to ulcerative colitis. We examined a cohort of 78 cases of inflammatory bowel disease: 50 ulcerative colitis and 38 Crohn's disease. We identified treatment-naive biopsies. Additionally, four cases of inflammatory bowel disease associated with autoimmune pancreatitis and 15 cases of lymphocytic/collagenous colitis were also identified. Immunohistochemical stains for IgG4 were performed. Biopsies from patients with ulcerative colitis showed significantly higher numbers of IgG4-bearing plasma cells than those with Crohn's disease (mean IgG4 counts per high-power field (hpf) 9.8 vs 2.8, P=0.001). Samples from 19 (38%) ulcerative colitis patients had IgG4 counts >10/hpf, compared with only two (5%) patients with Crohn's disease; the sensitivity and specificity of a cutoff at 10 IgG4-positive plasma cells per hpf was 38 and 95%, respectively. Among individuals <18 years, there were no statistically differences in the IgG4 counts between the two subforms of inflammatory bowel disease. Among adult patients, a cutoff of 5 IgG4+ plasma cells distinguished ulcerative colitis from Crohn's disease with a sensitivity of 53% and specificity of 83%. In comparison to inflammatory bowel disease, patients with lymphocytic/collagenous colitis showed significantly lower numbers of IgG4-positive plasma cells (P=0.0001). Ulcerative colitis with pancolitis showed higher numbers of IgG4-bearing plasma cells (mean IgG4 12.8 vs 5.8 per hpf; P=0.09). An immunohistochemical stain for IgG4 may aid in making the distinction between ulcerative colitis and Crohn's disease (with exclusion of the pediatric cases), albeit with a relatively low sensitivity. This study also provides additional support to the hypothesis that a subset of ulcerative colitis cases is associated with a Th2 response

Low temperature synthesis of ZnSe nanoparticles

Synthesis of thioglycerol capped zinc selenide nanoparticles with a relatively narrow size distribution by a simple and inexpensive low temperature (~ 80 °C) wet chemical method is reported here. Main advantage of this method is the use of non-toxic precursors. The size of the nanoparticles can be varied easily by changing the concentration of the capping agent. The extracted nanoparticles remain stable under normal atmospheric conditions and can be redispersed in suitable solvents. The sharp absorption features obtained in the UV-Visible absorption spectra reveal the formation of monodispersed ZnSe nanoparticles. The nanoparticles were characterized using X-ray photoelectron spectroscopy, X-ray diffraction, UV-Visible absorption spectroscopy, photoluminescence and transmission electron microscopy

Retinal changes in pregnancy-induced hypertension

Aims: The aim was to determine the prevalence of retinal changes in pregnancy-induced hypertension (PIH) and any association between the retinal changes and age, parity, blood pressure, proteinuria, and severity of the disease. Settings and Design: Hospital-based cross-sectional study. Materials and Methods: All the patients admitted with a diagnosis of PIH were included in this study. Age, gravida, gestation period, blood pressure, and proteinuria were noted from the case records. Fundus examination was done with a direct ophthalmoscope. The findings were noted and were analyzed using SPSS program. Results: A total of 150 patients of PIH were examined. The mean age of patients was 25.1 years. The gestation period ranged from 27 weeks to 42 weeks; 76 (50.67%) were the primi gravida. 92 (61.33%) patients had gestational hypertension, 49 (32.67%) patients had preeclampsia, and 9 (6%) had eclampsia. Retinal changes (hypertensive retinopathy) were noted in 18 (12%) patients - Grade 1 in 12 (8%) and Grade 2 in 6 (4%). Hemorrhages or exudates or retinal detachment were not seen in any patient. There was statistically significant positive association of retinal changes and blood pressure (P = 0.037), proteinuria (P = 0.0005), and severity of the PIH (P = 0.004). Conclusions: Retinal changes were seen in 12% of patients with PIH. Occurrence of hypertensive retinopathy in PIH cases has been decreased due to better antenatal care and early detection and treatment of PIH cases. There is a greater chance of developing retinopathy with increase in blood pressure, severity of PIH, and proteinuria in cases of PIH

Shape and Size Control of Artificial Cells for Bottom-Up Biology

Bottom-up biology is an expanding research field that aims to understand the mechanisms underlying biological processes via in vitro assembly of their essential components in synthetic cells. As encapsulation and controlled manipulation of these elements is a crucial step in the recreation of such cell-like objects, microfluidics is increasingly used for the production of minimal artificial containers such as single-emulsion droplets, double-emulsion droplets, and liposomes. Despite the importance of cell morphology on cellular dynamics, current synthetic-cell studies mainly use spherical containers, and methods to actively shape manipulate these have been lacking. In this paper, we describe a microfluidic platform to deform the shape of artificial cells into a variety of shapes (rods and discs) with adjustable cell-like dimensions below 5 μm, thereby mimicking realistic cell morphologies. To illustrate the potential of our method, we reconstitute three biologically relevant protein systems (FtsZ, microtubules, collagen) inside rod-shaped containers and study the arrangement of the protein networks inside these synthetic containers with physiologically relevant morphologies resembling those found in living cells