deliVERy of optimal blood pressure coNtrol in afrICA (VERONICA)-Nigeria study: Rationale and design of a randomized clinical trial.

BACKGROUND: Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension. METHODS: This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice. CONCLUSION: The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults. TRIAL REGISTRATION: PACTR202107579572114.

Low-Dose Triple-Pill vs Standard-Care Protocols for Hypertension Treatment in Nigeria: A Randomized Clinical Trial.

Importance: With the high burden of hypertension in sub-Saharan Africa, there is a need for effective, safe and scalable treatment strategies. Objective: To compare, among Black African adults, the effectiveness and safety of a novel low-dose triple-pill protocol compared with a standard-care protocol for blood pressure lowering. Design and Setting: Randomized, parallel-group, open-label, multicenter trial conducted in public hospital-based family medicine clinics in Nigeria. Participants: Black African adults with uncontrolled hypertension (≥140/90 mm Hg) who were untreated or receiving a single blood pressure-lowering drug. Interventions: Participants were randomly allocated to low-dose triple-pill or standard-care protocols. The triple-pill protocol involved a novel combination of telmisartan, amlodipine, and indapamide in triple one-quarter, one-half, and standard doses (ie, 10/1.25/0.625 mg, 20/2.5/1.25 mg, and 40/5/2.5 mg), with accelerated up-titration. The standard-care protocol was the Nigeria hypertension treatment protocol starting with amlodipine (5 mg). Main Outcomes and Measures: The primary effectiveness outcome was the reduction in home mean systolic blood pressure, and the primary safety outcome was discontinuation of trial treatment due to adverse events, both from randomization to month 6. Results: The first participant was randomized on July 19, 2022, and the last follow-up visit was on July 18, 2024. Among 300 randomized participants (54% female; mean age, 52 years; baseline mean home blood pressure, 151/97 mm Hg; and clinic blood pressure, 156/97 mm Hg), 273 (91%) completed the trial. At month 6, mean home systolic blood pressure was on average 31 mm Hg (95% CI, 28 to 33 mm Hg) lower in the triple-pill protocol group and 26 mm Hg (95% CI, 22 to 28 mm Hg) lower in the standard-care protocol group (adjusted difference, -5.8 mm Hg [95% CI, -8.0 to -3.6]; P < .001]). At month 6, clinic blood pressure control (<140/90 mm Hg) was 82% vs 72% (risk difference, 10% [95% CI, -2% to 20%]) and home blood pressure control (<130/80 mm Hg) was 62% vs 28% (risk difference, 33% [95% CI, 22% to 44%]) in the triple-pill compared with the standard-care protocol group; these were 2 of 21 prespecified secondary effectiveness end points. No participants discontinued trial treatment due to adverse events. Conclusions and Relevance: Among Black African adults with uncontrolled hypertension, a low-dose triple-pill protocol achieved better blood pressure lowering and control with good tolerability compared with the standard-care protocol. Trial Registration: Pan African Clinical Trials Registry Identifier: PACTR202107579572114.

Building communities of practice through case-based e-learning to prevent and manage TB among people living with HIV-India.

BACKGROUND: Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV. To strengthen HIV-TB service delivery, case-based e-learning was introduced to health care providers at Antiretroviral Therapy centres (ARTc). METHODS: We implemented a hub and spoke model to deliver biweekly, virtual, case-based e-learning at select ARTc (n = 115), from four states of India-Delhi, Uttar Pradesh, Andhra Pradesh and Tamil Nadu. We evaluated feasibility and acceptability of case-based e-learning and its impact on professional satisfaction, self-efficacy, knowledge retention using baseline and completion surveys, session feedback, pre-and post-session assessments. We reviewed routine programmatic data and patient outcomes to assess practices among participating ARTc. RESULTS: Between May 2018 and September 2020, 59 sessions were conducted with mean participation of 55 spokes and 152 participants. For 95% and 88% of sessions ≥ 80% of respondents agreed that topics were clear and relevant to practice, and duration of session was appropriate, respectively. Session participants significantly improved in perceived knowledge, skills and competencies (+ 8.6%; p = 0.025), and technical knowledge (+ 18.3%; p = 0.04) from baseline. Participating ARTc increased TB screening (+ 4.2%, p < 0.0001), TB diagnosis (+ 2.7%, p < 0.0001), ART initiation (+ 4.3%, p < 0.0001) and TB preventive treatment completion (+ 5.2%, p < 0.0001). CONCLUSION: Case-based e-learning is an acceptable and effective modus of capacity building and developing communities of practice to strengthen integrated care. E-learning could address demand for accessible and sustainable continuing professional education to manage complex diseases, and thereby enhance health equity. We recommend expansion of this initiative across the country for management of co-morbidities as well as other communicable and non-communicable diseases to augment the existing capacity building interventions by provide continued learning and routine mentorship through communities of practice.

The relationship between educational attainment and hiv prevalence among pregnant women attending antenatal clinics in six states of India: Sentinel surveillance from 2010 to 2017.

BACKGROUND: The National AIDS Control Programme provides support for HIV prevention services to pregnant women attending antenatal care (ANC) clinics through testing, kit delivery, counseling, and treatment services. The impact of HIV prevention programs in the general population is assessed by monitoring trends and progress made against the HIV epidemic among pregnant women attending ANC clinics during HIV Sentinel Surveillance (HSS). OBJECTIVES: This study explores the association of HIV risk with educational attainment for Indian women across different age groups from four repeated cross-sectional surveillance of antenatal clinics in six states from the southern part of India. METHODS: Data collected from the repeated cross-sectional HSS conducted during the year 2010-2011 (baseline) and 2016-2017 (end line) across six states were used for this analysis. The total sample size was 94,266 at baseline and 99,434 at end line. In the logistic regression analysis, we focused on identifying the association between educational attainment, and HIV prevalence adjusting for period effects across two age groups for women attending ANC clinics. RESULTS: The analysis showed an inverse association between education and HIV risk across different age groups. The age-segregated and survey period adjusted analysist showed that for older women (≥25 years), the HIV risk in 2010 ranged from 41% lower among 5th Grade to 80% lower among postgraduates than illiterates. For the <25 year age group, this risk of HIV for pregnant women was 35% to 49% lower. CONCLUSIONS: To ensure an effective national response to control and prevent HIV infection, policymakers in India need to focus on ≥25 years' age group of women attending ANC for designing educational interventions to reduce HIV risk as well as the prevention of mother-to-child transmission of HIV.

PHI-base: a new interface and further additions for the multi-species pathogen-host interactions database.

The pathogen-host interactions database (PHI-base) is available at www.phi-base.org PHI-base contains expertly curated molecular and biological information on genes proven to affect the outcome of pathogen-host interactions reported in peer reviewed research articles. In addition, literature that indicates specific gene alterations that did not affect the disease interaction phenotype are curated to provide complete datasets for comparative purposes. Viruses are not included. Here we describe a revised PHI-base Version 4 data platform with improved search, filtering and extended data display functions. A PHIB-BLAST search function is provided and a link to PHI-Canto, a tool for authors to directly curate their own published data into PHI-base. The new release of PHI-base Version 4.2 (October 2016) has an increased data content containing information from 2219 manually curated references. The data provide information on 4460 genes from 264 pathogens tested on 176 hosts in 8046 interactions. Prokaryotic and eukaryotic pathogens are represented in almost equal numbers. Host species belong ∼70% to plants and 30% to other species of medical and/or environmental importance. Additional data types included into PHI-base 4 are the direct targets of pathogen effector proteins in experimental and natural host organisms. The curation problems encountered and the future directions of the PHI-base project are briefly discussed.

The Pathogen-Host Interactions database (PHI-base): additions and future developments.

Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s).

Use of Guideline-Recommended Heart Failure Drugs in High-, Middle-, and Low-Income Countries: A Systematic Review and Meta-Analysis.

Optimal use of guideline-directed medical therapy (GDMT) can prevent hospitalization and mortality among patients with heart failure (HF). We aimed to assess the prevalence of GDMT use for HF across geographic regions and country-income levels. We systematically reviewed observational studies (published between January 2010 and October 2020) involving patients with HF with reduced ejection fraction. We conducted random-effects meta-analyses to obtain summary estimates. We included 334 studies comprising 1,507,849 patients (31% female). The majority (82%) of studies were from high-income countries, with Europe (45%) and the Americas (33%) being the most represented regions, and Africa (1%) being the least. Overall prevalence of GDMT use was 80% (95% CI 78%-81%) for ß-blockers, 82% (80%-83%) for renin-angiotensin-system inhibitors, and 41% (39%-43%) for mineralocorticoid receptor antagonists. We observed an exponential increase in GDMT use over time after adjusting for country-income levels (p < 0.0001), but significant gaps persist in low- and middle-income countries. Multi-level interventions are needed to address health-system, provider, and patient-level barriers to GDMT use.

Can training over phone calls help improve outcomes for COVID-19 positive patients under home isolation? An analysis of the COVID-19 Care Companion Program in Punjab, India.

Background: Phone-supported recovery of COVID-19 patients in home isolation could be an effective way of addressing COVID-19 in contexts with limited resources. The COVID-19 Care Companion Program (CCP) is one such intervention, designed to support patients and their caregivers in remote, evidence-based management of COVID-19 symptoms. Objective: To estimate the effect of providing phone-based training to COVID-19 patients and their caregivers on the likelihood of hospitalizations and mortality. Methods: A pragmatic randomized trial was conducted to assess the effect of a novel phone-based training program on COVID-19 home-isolated patient outcomes. The analysis compared the outcomes of death and hospitalizations in the teletraining intervention group (CCP) to those receiving standard of care (SoC). Results: Logistic regression models adjusted for age, gender, education, occupation, and poverty, as measured by family possession of Below Poverty Line (BPL) card, were used to look at the effect of intervention on hospitalization and mortality. While the CCP intervention had no effect on 21-day mortality (OR 0.64; 95% CI, 0.19 to 2.12), it was associated with a 48% reduction in 21-day hospitalization (OR 0.52; 95% CI, 0.31 to 0.90). Conclusion: COVID-19 CCP teletraining intervention reduced the rate of hospitalization, potentially reducing the burden on hospitals.

Perceptions and practice of physicians treating HIV patients in the private sector in India: A cross sectional study.

Objectives: To understand the perceptions of the private HIV physicians regarding HIV case management and reporting practices followed by the National AIDS Control Programme, India. Methods: We conducted this cross-sectional study among 142 private practitioners attending Chennai ART Symposium 2017, from five south Indian states. We used a pre-structured questionnaire to collect information on demography, qualification, the number of HIV patients treated, ART regimen, and the reporting practices. EpiInfo 7.2 was used for data analysis. Results: Out of the 142 private practitioners, 89 (63%) responded. All respondents had diagnosed and/or treated at least 10 HIV patients in the past 12 months. About 42% of respondents reported attending an orientation program on ART by the State AIDS Control Society (SACS). Seventy percent of respondents were aware of the National AIDS Control Organization's (NACO) Public Private Partnership (PPP) initiative for private clinics, and 44% (39) reported sharing monthly reports with SACS. However, 77% of physicians were not interested to enroll due to increased paperwork and complicated reporting mechanisms. Conclusion: Private sector physicians treating People Living with HIV (PLHIV) are aware of NACO guidelines and reporting mechanisms. A simplified reporting process and an engaging platform are needed to facilitate reporting.

Ocular sequelae in severe COVID-19 recovered patients of second wave.

Purpose: To evaluate the retinal microvascular changes in patients, recovered from severe COVID-19 during the second wave of the pandemic in North India. Methods: In this observational cross-sectional study, 70 eyes of 35 patients who recovered from severe COVID-19 during the second wave underwent detailed ophthalmic evaluation 4-6 weeks after discharge. Twelve controls were also enrolled, and the difference in the findings between the case and control groups on optical coherence tomography (OCTA) were studied. Result: The ages of study participants ranged from 27 to 60 years with the male:female ratio being 1.05:1. The fundus changes suggestive of ischemia in the form of cotton wool spots and vascular tortuosity were seen in 25 eyes (35.71%). Increased venous tortuosity was the most common finding seen in 23 eyes (32.85%), of which 10 eyes (28.57%) had concurrent hypertensive retinopathy (HTR) changes. There was a significant reduction in the mean vascular density (VD) and perfusion density (PD) for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at inner, outer ring, and whole (P < 0.05). Foveal avascular zone was significantly enlarged in both the SCP (P = 0.01) and the DCP (P = 0.03). The mean ganglion cell-inner plexiform layer (GC-IPL) was significantly reduced in comparison to controls (P < 0.001). Conclusion: Severe COVID-19 can result in microvascular changes at the macula in the form of reduction in vascular and perfusion density, which can be evaluated using OCTA. As structural changes precede functional changes, a close watch is recommended in patients showing compromise in retinal microvasculature.

Impact of family-centred postnatal training on maternal and neonatal health and care practices in district hospitals in two states in India: a pre-post study.

BACKGROUND AND OBJECTIVES: The Care Companion Program (CCP) is an in-hospital multitopic skill-based training programme provided to families to improve postdischarge maternal and neonatal health. The states of Punjab and Karnataka in India piloted the programme in 12 district hospitals in July 2017, and no study to date has evaluated its impact. METHODS: We compared telephonically self-reported maternal and neonatal care practices and health outcomes before and after the launch of the CCP programme in 11 facilities. Families in the preintervention group delivered between May to June 2017 (N=1474) while those in the intervention group delivered between August and October 2017 (N=3510). Programme effects were expressed as adjusted risk ratios obtained from logistic regression models. RESULTS: At 2-week postdelivery, the practice of dry cord care improved by 4% (RR=1.04, 95% CI 1.02 to 1.06) and skin-to-skin care by 78% (RR=1.78, 95% CI 1.37 to 2.27) in the postintervention group as compared with preintervention group. Furthermore, newborn complications reduced by 16% (RR=0.84, 95% CI 0.76 to 0.91), mother complications by 12% (RR=0.88, 95% CI 0.79 to 0.97) and newborn readmissions by 56% (RR=0.44, 95% CI 0.31 to 0.61). Outpatient visits increased by 27% (RR=1.27, 95% CI 1.10 to 1.46). However, the practice of exclusive breastfeeding, unrestricted maternal diet, hand-hygiene and being instructed on warning signs were not statistically different. CONCLUSION: Postnatal care should incorporate predischarge training of families. Our findings demonstrate that it is possible to improve maternal and neonatal care practices and outcomes through a family-centered programme integrated into public health facilities in low and middle-income countries.

Rhino-Orbito-Cerebral-Mucormycosis During the COVID-19 Second Wave in 2021 - A Preliminary Report from a Single Hospital.

PURPOSE: To list the clinico-epidemiological profile and possible risk factors of COVID-19 associated rhino-orbital-cerebral mucormycosis (CA-ROCM) patients presenting to a COVID dedicated hospital during the second wave of COVID-19 in India. PATIENTS AND METHODS: A cross-sectional, single-center study was done on 60 cases of probable CA-ROCM based on clinical features and supportive diagnostic nasal endoscopic findings and/or radiologic findings. Patients with recent or active COVID-19 were included. The demographic profile, clinical features, possible risk factors and diagnostic workup (microbiological, pathological and radiological) were analysed to identify the triggering factors for CA-ROCM. RESULTS: The age of patients ranged from 29 to 75 years and male-female ratio was 3:1. The duration between the first positive COVID report and onset of CA-ROCM was 0 to 47 days. Forty-nine (81.66%) patients had a recent COVID infection and 11 (18.33%) had active COVID infection at presentation. Thirty-five patients (58%) had ocular/orbital involvement at presentation. In the affected eye, 10 had no perception of light and in the rest visual acuity ranged from log MAR 0 to +1.5. Ocular manifestations were ptosis (29), ophthalmoplegia (23), periocular tenderness and edema (33), proptosis (14), black discoloration of eyelids (3), facial palsy (3), endophthalmitis (4), retinal artery occlusion (8), disc edema (4) and disc pallor (5). Twenty-two (25%) patients had neither received steroids nor oxygen. Thirty patients (50%) were managed with oxygen while 38 patients (63.3%) with systemic steroids. The most common risk factor was diabetes in 59 patients. The average glycosylated hemoglobin (HbA1c) was 10.31 ± 2.59%. Systemic Amphotericin B was started in all the patients. Radical surgical debridement was performed in 12 patients and the remaining were planned. CONCLUSION: SARS-CoV-2 variant with accompanying glycaemic dysregulation was found to be the triggering factor for the epidemic of CA-ROCM.

Factors associated with non-adherence to antiretroviral therapy among female sex workers living with HIV in Hyderabad, India.

We determined factors associated with non-adherence (consuming <90% of monthly antiretroviral therapy) among female sex workers (FSWs). An interviewer-administered questionnaire was used in a sample of 100 South Indian FSWs living with HIV. We examined demographics, food insecurity, side effects, stigma, alcohol/substance use and self-efficacy. Non-adherence was assessed by self-report, pill-count and combined measures. Prevalence ratios and 95% confidence intervals (CIs) were calculated at p-value <0.1. Thirty-seven percent (33/90) of FSWs were non-adherent by pill-count, 29% (28/95) by self-report and 52% (51/99) by the combined measure. Seventy-six percent (76/100) of FSWs reported experience of at least one form of food insecurity in the past six months. In the regression analysis, arrest in the past year was independently associated with the combined measure of non-adherence (crude prevalence ratios 1.7, 95% CI 1.0-2.8). A successful combination adherence intervention should consider several of the socio-behavioral factors identified in this study including arrest and food insecurity.

Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007-2011): Evidence leading to policy enhancement.

BACKGROUND: Globally, India has the world's highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP. OBJECTIVE: To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment. METHODS: This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics. RESULTS: In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92-125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202-381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and continuation phase (CP); cavitary disease; prior treatment episodes characterized by re-treatment regimen taken twice, longer duration and more episodes of treatment; any weight loss during treatment; males and additional resistance to first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment success, half of the success (54.8%) seen in Ofloxacin sensitive patients. Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55) significantly doubled and quadrupled the chances for culture conversion respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also significantly reduced the odds of unfavorable treatment outcomes (p value ≤0.05) in multinomial logistic regression model. CONCLUSION: India's initial MDR-TB patients' cohort treated under the RNTCP experienced poor treatment outcomes. To address the factors associated with poor treatment outcomes revealed in our study, a systematic multi-pronged approach would be needed. A series of policies and interventions have been developed to address these factors to improve DR-TB treatment outcomes and are being scaled-up in India.

Binding of resveratrol to the minor groove of DNA sequences with AATT and TTAA segments induces differential stability.

Interactions of a natural stilbene compound, resveratrol with two DNA sequences containing AATT/TTAA segments have been studied. Resveratrol is found to interact with both the sequences. The mode of interaction has been studied using absorption, steady state fluorescence and circular dichroism spectroscopic techniques. UV-visible absorption and fluorescence studies provided the information regarding the binding constants and the stoichiometry of binding, whereas circular dichroism studies depicted the structural changes in DNA upon resveratrol binding. Our results evidenced that, though resveratrol showed similar affinity to both the sequences, the mode of interactions was different. The binding constants of resveratrol to AATT/TTAA sequences were found to be 7.55×105M-1 and 5.42×105M-1 respectively. Spectroscopic data evidenced for a groove binding interaction. Melting studies showed that the binding of resveratrol induces differential stability to the DNA sequences d(CGTTAACG)2 and d(CGAATTCG)2. Fluorescence data showed a stoichiometry of 1:1 for d(CGAATTCG)2-resveratrol complex and 1:4 for d(CGTTAACG)2-resveratrol complex. Molecular docking studies demonstrated that resveratrol binds to the minor groove region of both the sequences to form stable complexes with varied atomic contacts to the DNA bases or backbone. Both the complexes are stabilized by hydrogen bond formation. Our results evidenced that modulation of DNA sequence within the same bases can greatly alter the binding geometry and stability of the complex upon binding to small molecule inhibitor compounds like resveratrol.

Comparison of Bone Mineral Density between Urban and Rural Areas: Systematic Review and Meta-Analysis.

BACKGROUND: Studies from high income countries (HIC) have generally shown higher osteoporotic fracture rates in urban areas than rural areas. Low bone mineral density (BMD) increases susceptibility to fractures. This review aimed to assess whether urbanicity is consistently associated with lower BMD globally. METHOD: Ovid MEDLINE, EMBASE, and Global Health (-April 2013) were searched for articles investigating differences in bone mineral content (BMC) or BMD between urban and rural areas. Ratio of means (RoM) of BMD were used to estimate effect sizes in meta-analysis, with an exception for one study that only presented BMC data. RESULTS: Fifteen articles from eleven distinct populations were included in the review; seven populations from four high income countries and four from three low and middle income countries (LMIC). Meta-analysis showed conflicting evidence for urban-rural difference in BMD; studies from high income countries generally showed higher BMD in rural areas while the results were more mixed in studies from low and middle income countries (HIC RoM = 0.05; 95% CI: 0.03 to 0.06; LMIC RoM = -0.04: 95% CI: -0.1 to 0.01). CONCLUSIONS: Urban-rural differences of bone mineral density may be context-specific. BMD may be higher in urban areas in some lower income countries. More studies with robust designs and analytical techniques are needed to understand mechanisms underlying the effects of urbanization on bone mass accrual and loss.

Microhabitat distribution of some monogenoideans, parasitizing the gills of Wallago attu (Bl. and Sch., 1801) and their seasonal variation.

The parasitic microhabitat distribution of the monogenoideans Thaparocleidus wallagonoius Jain, 1952, Mizelleus indicus Jain, 1957and T. gomtius Jain, 1957 parasitizing the gills of a fresh-water demersal Wallago attu and their seasonal variations were investigated in the present study. The microhabitat preferences of these species were observed. The gill segments and gill areas were the most important factors segregating the monogenoidean parasites on gills, not their abundance. Low niche overlap was found within each of the four gill arches and parasites were segregated in the same microhabitats within each gill arch. The distribution of parasites was independent of the left or right side of gill. The distribution plots in our study indicated that the anterior segment of first and fourth gill arches were more preferred site of infection. Seasonal variation of parasites, recorded during 2006 & 2007, in male and female hosts was also investigated. Due to ectoparasitic nature and high host specificity exhibited by the species of monogenoidea, studies on their seasonal dynamics are very significant as they could contribute significantly to the understanding of their biological adaptations to their environment.

Discriminant analysis: A supportive tool for monogenoidean taxonomy.

Data on the measurements of haptoral parts of 47 parasite species of Bychowskyella (1), Cornudiscoides (2) and Thaparocleidus (3), found on Indian freshwater catfish, were gathered from previously reported studies. Based on six morphometric variables concerning haptors, these species were subjected to discriminant analysis in order to more accurately distinguish their generic placement. This paper describes a comparative study of several classification models. Using the original variables in the study, a simple linear discriminant analysis model was constructed and models using principal components (PC) for discrimination have also been explored. The effectiveness of these models is measured in terms of percentage of correct classification. Quadratic discriminant models using original variables and their principal components provided the highest (95%) correct classification for Bychowskyella (1). Species of Thaparocleidus (3) were correctly classified using dorsal and ventral hard-part measurements (100%) as well as hook measurements. The highest percentage (75%) of correct classification for Cornudiscoides (2) was achieved through a quadratic discriminant model using hook measurements.

Developmental and molecular characterization of emerging beta- and gammadelta-selected pre-T cells in the adult mouse thymus.

The first checkpoint in T cell development, beta selection, has remained incompletely characterized for lack of specific surface markers. We show that CD27 is upregulated in DN3 thymocytes initiating beta selection, concomitant with intracellular TCR-beta expression. Clonal analysis determined that CD27high DN3 cells generate CD4+CD8+ progeny with more than 90% efficiency, faster and more efficiently than the CD27low majority. CD27 upregulation also occurs in gammadelta-selected DN3 thymocytes in TCR-beta-/- mice and in IL2-GFP transgenic reporter mice where GFP marks the earliest emerging TCR-gammadelta cells from DN3 thymocytes. With CD27 to distinguish pre- and postselection DN3 cells, a detailed gene expression analysis defined regulatory changes associated with checkpoint arrest, with beta selection, and with gammadelta selection. gammadelta selection induces higher CD5, Egr, and Runx3 expression as compared to beta selection, but it triggers less proliferation. Our results also reveal differences in Notch/Delta dependence at the earliest stages of divergence between developing alphabeta and gammadelta T-lineage cells.