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Abstract Background Validated and comprehensive tools to measure treatment burden are needed for healthcare professionals to understand the treatment burden of patients in China. The study aimed to translate and validate the Chinese version of Patient Experience with Treatment and Self-management (PETS vs. 2.0) in patients with multimorbidity in primary care. Methodology The translation process of the 60-item PETS vs. 2.0 followed the Functional Assessment of Chronic Illness Therapy (FACIT) Translation, Formatting, and Testing Guidelines. Computer-assisted assessments were conducted in adult primary care patients with multimorbidity from three general out-patient clinics in Hong Kong. A sample of 502 patients completed the assessments from July to December 2023. Internal reliability was examined using Cronbach’s alphas for each domain of the PETS vs. 2.0. Concurrent validity was assessed through the correlations between different domains of PETS vs. 2.0 with established measures including quality of life, frailty, and depression. Confirmatory Factor Analysis (CFA) with maximum likelihood method was carried out to assess the construct validity. Results The mean age of participants was 64.9 years old and 56.2% were female. Internal consistency reliability was acceptable (alpha ≥ 0.70) for most domains. Higher scores of PETS domains were significantly correlated with worse quality of life, higher level of frailty, and more depressive symptoms (p

Abstract Background There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. Methods This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (

Abstract Mounting evidence demonstrates that intimate partners sharing risk factors have similar propensities for chronic conditions such as hypertension. The objective was to study whether spousal hypertension was associated with one’s own hypertension status independent of known risk factors, and stratified by socio-demographic subgroups (age, sex, wealth quintile, caste endogamy). Data were from heterosexual married couples (n = 50,023, women: 18–49 years, men: 21–54 years) who participated in the National Family Health Survey-V (2019–2021). Hypertension was defined as self-reported diagnosis of hypertension or average of three blood pressure measurements ≥ 140 systolic or 90 mmHg diastolic BP. Among married adults, the prevalence of hypertension among men (38.8 years [SD 8.3]) and women (33.9 years [SD 7.9]) were 29.1% [95% CI 28.5–29.8] and 20.6% [95% CI 20.0–21.1] respectively. The prevalence of hypertension among both partners was 8.4% [95% CI 8.0–8.8]. Women and men were more likely to have hypertension if their spouses had the condition (husband with hypertension: PR 1.37 [95% CI 1.30–1.44]; wife with hypertension: PR 1.32 [95% CI 1.26–1.38]), after adjusting for known risk factors. Spouse’s hypertension status was consistently associated with own status across all socio-demographic subgroups examined. These findings present opportunities to consider married couples as a unit in efforts to diagnose and treat hypertension.

BackgroundNoncommunicable diseases (NCDs), particularly diabetes and chronic kidney diseases, pose a significant health burden in Thailand, especially among socioeconomically disadvantaged populations. The existing primary health care system faces challenges in providing optimal care for NCDs due to inadequate primary care workforce. The SMARThealth program offers a technology-based solution to enhance NCD management through task-sharing among nonphysician health care workers. ObjectiveThis study aims to adapt and implement the SMARThealth Diabetes program in rural Thailand to improve diabetes management. The main objectives are to (1) adapt, validate, and integrate the SMARThealth Diabetes program for improving the management of type 2 diabetes mellitus at the primary health care level; and (2) to determine the feasibility and acceptability of the SMARThealth Diabetes program in rural communities of Thailand. MethodsA pragmatic, type 2 hybrid effectiveness or implementation, parallel-group cluster randomized controlled trial of 12 months duration and involving 51 subdistrict health offices in rural communities of Kamphaeng Phet province, Thailand, will be conducted. The intervention arm will receive the SMARThealth Diabetes program, including workforce restructuring, clinical decision support system, and continuous performance monitoring, while the control arm will continue with usual practice. Data will be collected using the SMARThealth platform and will be stored on a server in Thailand. The primary outcome measure will be the change in mean hemoglobin A1c (HbA1c) measured at randomization and 12 months from randomization between the intervention and control clusters. Secondary outcomes will include the difference in change in albuminuria status, estimated glomerular filtration rate, systolic blood pressure, and low-density lipoprotein cholesterol level. The analysis for change in HbA1c between baseline and end of study will be performed using linear mixed models. Any imbalances between the 2 arms will be addressed by sensitivity analyses. Additionally, a mixed methods process evaluation will be conducted to assess the implementation process, that will include in-depth interviews and focus group discussions, in addition to the quantitative data collected during the implementation process. The qualitative data will be thematically analyzed to explore factors that promote or inhibit the implementation and maintenance of the program. ResultsThe data collection commenced in November 2022, and the results will be ready for publication by the first quarter of 2025. Effectiveness of the intervention package will be assessed by change in mean HbA1c measures, and detailed feasibility, barriers, and enablers for the implementation of the intervention will be documented through a detailed process evaluation. ConclusionsThe study protocol outlines a novel approach to enhancing diabetes management in rural Thailand through digital technology–based interventions that will facilitate task-sharing among health care workers. This can help inform future strategies for improving NCD care in low-resource settings globally. Trial RegistrationThai Clinical Trials Registry TCTR20200322006; https://www.thaiclinicaltrials.org/show/TCTR20200322006 International Registered Report Identifier (IRRID)DERR1-10.2196/59266

Deep sea is a vast, dark, and difficult-to-access terrain and is now looked upon as a unique niche harboring diverse microorganism. We used a metataxonomic approach to decipher the microbial diversity present in the water column (surface to near bottom), water overlaying the sediments, and the deep-sea sediments (up to 35 cm) from the Indian Contract Region (ICR) in the Central Indian Ocean Basin (CIOB). Samples were collected from #IRZ (Impact Reference Zone), #PRZ (Potential Reference Zone), and #BC20 (Control site, outside potential mining area) with an average water depth of 5,200 m. 16S rRNA (V3–V4 region) amplicon sequencing on the MiSeq platform resulted in 942,851 ASVs across 65 water and sediment samples. Higher prokaryotic diversity was observed below 200 m in the water column to the seafloor. Proteobacteria was the most dominant bacterial phylum among all the water samples while Firmicutes, Actinobacteria and, Bacteroidota dominated the sediments. Sediment (below 10 cm) was co-dominated by Firmicutes. Thermoplasmata was the dominant archaeal group in the water column while Crenarchaeota was in the sediments. BC20 was less diverse than IRZ and PRZ. Deep Sea microorganisms could play a vital role in the mineralization processes, nutrient cycling, and also different biogeochemical cycles.

Abstract Globally, over 200 million women and girls have been subjected to Female Genital Mutilation (FGM). This practice, illegal in most countries, often happens in unsanitary conditions and without clinical supervision with consequent bleeding and infection. However, little is known about its contribution to the global epidemiology of child mortality. We matched data on the proportion of girls of a given age group subject to FGM to age-gender-year specific mortality rates during 1990–2020 in 15 countries where FGM is practised. We used fixed-effects regressions to separate the effect of FGM on mortality-rates from variation in mortality in that country in that year. Using our estimated effect, we calculated total annual excess mortality due to FGM. Our estimates imply that a 50% increase in the number of girls subject to FGM increases their 5-year mortality rate by 0.075 percentage point (95% CI $$0\cdot 065$$ 0 · 065 – $$0\cdot 085$$ 0 · 085 ). This increased mortality rate translates into an estimated 44,320 excess deaths per year across countries where FGM is practised. These estimates imply that FGM is a leading cause of the death of girls and young women in those countries where it is practised accounting for more deaths than any cause other than Enteric Infections, Respiratory Infections, or Malaria.

Abstract We investigated the effect of two dosing regimens of oral iron on iron status and hematological parameters in patients with CKD. In this single center, open label, randomized, active controlled clinical trial, stable adult patients with CKD stage G3–4 with percentage transferrin saturation (%TSAT) ≤ 30% and serum ferritin ≤ 500 ng/ml were eligible. Participants were randomized to receive either 100 mg of ferrous ascorbate once daily (OD group) or 100 mg of ferrous ascorbate twice daily (BD group, total daily dose 200 mg). The primary outcome was change in %TSAT between groups over 12 weeks. The secondary outcomes were changes in other iron status and hematological parameters, serum interleukin-6 (IL-6) and hepcidin. 80 participants were enrolled out of which 76 completed the study. Change in %TSAT was not significantly different between groups (β = − 1.43, 95% CI − 3.99 to 1.12, BD group as reference). The rise in serum ferritin was less in the OD group as compared to BD group (β = − 0.36, 95% CI − 0.61 to − 0.10) whereas MCHC increased in the OD group as compared to decrease in the BD group (β = 0.37, 95% CI 0.067–0.67). These observations need exploration to ascertain the impact of different oral iron dosing strategies in CKD.

Objectives Few studies have examined frailty in Indian adults, despite an increasing population of older adults and an escalating burden of chronic diseases. We aimed to study the prevalence and correlates of frailty in middle-aged and older Indian adults.Setting Cross-sectional data from Wave 1 of Longitudinal Ageing Study in India, conducted in 2017–2018 across all states and union territories, were used.Participants The final analytical sample included 57 649 participants aged 45 years and above who had information on frailty status.Primary outcome measure The deficits accumulation approach to measuring frailty was employed, creating a frailty index between 0 and 1, based on 40 deficits. Individuals with a frailty index of 0.25 or more were defined as ‘frail’.Results Prevalence of frailty among 45+ adults was 30%. 60+ women were two times as likely to be frail compared with 60+ men, after adjusting for a wide range of sociodemographic, economic and lifestyle factors. The sex difference was more pronounced in adults aged 45–59 years. Odds of hospitalisation in the last 12 months, and having falls in the past 2 years, were two times as high in frail adults compared with non-frail adults. Frail middle-aged and older adults had 33% and 39% higher odds, respectively, of having poor cognition than non-frail adults. The relative increase was higher in women for all three outcomes, although not statistically significant.Conclusions There needs to be careful consideration of sex differences when addressing frailty, particularly for optimising frailty interventions. Frailty, although typically assessed in older adults, was shown in this study to be also prevalent and associated with adverse outcomes in middle-aged Indian adults. More research into assessment of frailty in younger populations, its trajectory and correlates may help develop public health measures for prevention of frailty.

Abstract Acute kidney injury (AKI) increases the risk of morbidity, mortality, and progression to chronic kidney disease (CKD). There are few data on the risk of CKD following community-acquired AKI (CA-AKI) and its predictors from developing countries. We evaluated the association of a panel of serum and urine biomarkers at the time of hospital discharge with 4-month renal outcome in CA-AKI. Patients of either sex, aged between 18 and 70 years, with no underlying CKD, and with CA-AKI were recruited at the time of discharge from hospital in this prospective observational study. Levels of serum and urine biomarkers were analyzed and association between these markers and development of CKD, defined as eGFR

Summary: Background: The aim of this study is to assess the current status of metabolic and behavioural risk factors for cardiovascular diseases among the adult population in South and Southeast Asia using World Health Organization (WHO) STEPS data. Methods: We used WHO STEPS surveys data in ten South and Southeast Asian countries. Weighted mean estimates of prevalence of five metabolic risk factors and four behavioural risk factors were calculated by country and overall region. We used random-effects meta-analysis to generate country and regional pooled estimates of metabolic and behavioural risk factors, using the DerSimonian and Laird inverse-variance method. Finding: Around 48,434 participants aged 18–69 years were included in this study. Overall 32.00% (95% CI: 31.15–32.36) of individuals in the pooled sample had one metabolic risk factor, 22.10% (95% CI: 21.73–22.47) had two, and 12.38% had three or more (95% CI: 9.09–14.00). Twenty-four percent (95% CI: 20.00–29.00) of individuals in the pooled sample had only one behavioural risk factor, 49.00% (95% CI: 42.00–56.00) had two, and 22.00% had three or more (95% CI: 16.00–29.00). Risk of high three or more metabolic risk factors was higher among women, those of older age, and those with a higher education. Interpretation: The existence of multiple metabolic and behavioural risk factors among the South and Southeast Asian population demand appropriate prevention strategies to halt the progress of non-communicable disease burden within the region. Funding: Not applicable.

Objective Older male and female adults differ in key characteristics such as disease-specific life expectancy, health behaviours and clinical presentations and non-communicable disease multimorbidity (NCD-MM). Therefore, examining the sex differences in NCD-MM among older adults is vital, as this issue is understudied in low-income and middle-income country (LMIC) contexts such as India, and has been growing in the past few decades.Design Large scale nationally representative cross-sectional study.Settings and participants Longitudinal Ageing Study in India (LASI 2017–2018) had data on 27 343 men and 31 730 women aged 45+, drawn from a sample of 59 073 individuals across India.Primary and secondary outcomes measures We operationalised NCD-MM based on prevalence of the presence of two or more long-term chronic NCD morbidities. Descriptive statistics and bivariate analysis along with multivariate statistics were used.Results Women aged 75+ had a higher prevalence of multimorbidity as compared with men (52.1% vs 45.17%). NCD-MM was more common among widows (48.5%) than widowers (44.8%). The female-to-male ratios of ORs (RORs) for NCD-MM associated with overweight/obesity and prior history of chewing tobacco were 1.10 (95% CI: 1.01 to 1.20) and 1.42 (95% CI: 1.12 to 1.80), respectively. The female-to-male RORs show that the odds of NCD-MM were greater in formerly working women (1.24 (95% CI: 1.06 to 1.44)) relative to formerly working men. The effect of increasing NCD-MM on limitations in activities of daily living and instrumental ADL was greater in men than women but reversed for the hospitalisation.Conclusions We found significant sex differences in NCD-MM prevalence among older Indian adults, with various associated risk factors. The patterns underlying these differences warrant greater study, given existing evidence on differential longevity, health burdens and health-seeking patterns all of which operate in a larger structural context of patriarchy. Health systems in turn must respond to NCD-MM mindful of these patterns and aim to redress some of the larger inequities they reflect.

MicroRNAs (miRs) are a class of endogenously expressed non-coding RNAs that negatively regulate gene expression within cells and participate in maintaining cellular homeostasis. By targeting 3′ UTRs of target genes, individual miRs can control a wide array of gene expressions. Previous research has shed light upon the fact that aberrantly expressed miRs within cells can pertain to diseased conditions, such as cancer. Malignancies caused due to miRs are because of the high expression of onco-miRs or feeble expression of tumor-suppressing miRs. Studies have also shown miRs to engage in epithelial to mesenchymal transition (EMT), which allows cancer cells to become more invasive and metastasize. miR-21 is an onco-miR highly expressed in breast cancer cells and targets protein PTEN, which abrogates EMT. Therefore, we discuss an approach where in-house-developed peptidic amino sugar molecules have been used to target pre-miR-21 to inhibit miR-21 biogenesis, and hence antagonize its tumor-causing effect and inhibit EMT. Our study shows that small-molecule-based fine-tuning of miR expression can cause genotypic as well as phenotypic changes and also reinstates the potential and importance of nucleic acid therapeutics.

IntroductionAngiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are the antihypertensive drug class of choice in patients with chronic kidney disease (CKD). Head-to-head comparisons of the renal or non-renal outcomes between ACEI/ARB users and nonusers have not been conducted in all population groups. We examined the renal and cardiovascular outcomes in users and nonusers enrolled in the Indian Chronic Kidney Disease (ICKD) Study.MethodsA total of 4,056 patients with mild-moderate CKD were studied. Patients were categorized as ACEI/ARB users or nonusers. Major adverse kidney events [ESKD (end stage kidney disease), ≥50% decline in eGFR and kidney death], all-cause mortality, and cardiovascular mortality were analyzed over a median follow-up period of 2.64 (1.40, 3.89) years between the two groups.ResultsOut of a total of 4,056 patients, 3,487 (87%) were hypertensive. The adjusted sub-hazard ratio (SHR) and 95 % CI for ACEI /ARB users was 0.85 (0.71, 1.02) for MAKE, 0.80 (0.64, 0.99) for a 50% decline in eGFR, and 0.72 (0.58, 0.90) for ESKD. For cardiovascular mortality, ACEI/ARB users were at lower risk (SHR = 0.55, 95% CI: 0.34, 0.88). Diuretic users were at increased risk of all-cause mortality (HR = 1.95, 95% CI: 1.50, 2.53) and cardiovascular mortality (adjusted SHR = 1.73, 95% CI: 1.09, 2.73). There was non-significant association between the use of other antihypertensives and any of the end points.DiscussionACEI/ARB use is associated with slower rate of decline in eGFR in those with CKD stage 1-3. ACEI/ARB users had a significantly lower risk of renal outcomes, and cardiovascular mortality.

Abstract The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients—mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.

ABSTRACT Clinical and in vivo studies have demonstrated a role for hepatitis B virus (HBV)-encoded HBsAg (hepatitis B surface antigen) in HBV-related hepatocellular carcinoma (HCC); however, the underlying mechanisms remain largely unknown. Here, we investigated the role of HBsAg in regulating long noncoding RNAs (lncRNAs) involved in HCC progression. Our analysis of microarray data sets identified LINC00665 as an HBsAg-regulated lncRNA. Furthermore, LINC00665 is upregulated in liver samples from HBV-infected patients as well as in HCC, specifically in HBV-related HCC liver samples. These findings were supported by our in vitro data demonstrating that HBsAg, as well as HBV, positively regulates LINC00665 in multiple HBV cell culture models. Next, we evaluated the oncogenic potential of LINC00665 by its overexpression and CRISPR interference (CRISPRi)-based knockdown in various cell-based assays. LINC00665 promoted cell proliferation, migration, and colony formation but inhibited cell apoptosis in vitro. We then identified the underlying mechanism of HBsAg-mediated regulation of LINC00665. We used immunofluorescence assays to show that HBsAg enhanced the nuclear translocation of NF-κB factors in HepG2 cells, confirming that HBsAg activates NF-κB. Inhibition of NF-κB signaling nullified HBsAg-mediated LINC00665 upregulation, suggesting that HBsAg acts through NF-κB to regulate LINC00665. Furthermore, the LINC00665 promoter contains NF-κB binding sites, and their disruption abrogated HBsAg-induced LINC00665 upregulation. Finally, HBsAg facilitated the enrichment of the NF-κB factors NF-κB1, RelA, and c-Rel in the LINC00665 promoter. Taken together, this work shows that HBsAg can drive hepatocarcinogenesis by upregulating oncogenic LINC000665 through the NF-κB pathway, thereby identifying a novel mechanism in HBV-related HCC. IMPORTANCE Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Numerous reports indicate an oncogenic role for HBV-encoded HBsAg; however, the underlying mechanisms are not well understood. Here, we studied the role of HBsAg in regulating lncRNAs involved in hepatocarcinogenesis. We demonstrate that HBsAg, as well as HBV, positively regulates oncogenic lncRNA LINC00665. The clinical significance of this lncRNA is highlighted by our observation that LINC00665 is upregulated in liver samples during HBV infection and HBV-related HCC. Furthermore, we show LINC00665 can drive hepatocarcinogenesis by promoting cell proliferation, colony formation, and cell migration and inhibiting apoptosis. Taken together, this work identified LINC00665 as a novel gene through which HBsAg can drive hepatocarcinogenesis. Finally, we show that HBsAg enhances LINC00665 levels in hepatocytes by activating the NF-κB pathway, thereby identifying a novel mechanism by which HBV may contribute to HCC.

Summary: Background: Modifiable non-communicable disease (NCD) risk factors are becoming increasingly common among adolescents, with clustering of these risk factors in individuals of particular concern. The aim of this study was to assess global status of clustering of common modifiable NCD risk factors among adolescents. Methods: We used latest available data from nationally representative survey for 140 countries, namely the Global School-based Student Health Survey, the Health Behaviour in School-Aged Children and the longitudinal study of Australian Children. Weighted mean estimates of prevalence with corresponding 95% confidence intervals of nine NCD risk factors - physical inactivity, sedentary behaviour, insufficient fruits and vegetable consumption, carbonated soft drink consumption, fast food consumption, tobacco use, alcohol consumption and overweight/obesity - were calculated by country, region and sex. Findings: Over 487,565 adolescents, aged 11–17 years, were included in this study. According to trend analysis, prevalence of four or more NCD risk factors increased gradually over time. Prevalence of four or more NCD risk factors was 14.8% in 2003–2007 and increased to 44% in 2013–2017, an approximately three-fold increase (44.0%). Similar trends were also observed for three and two risk factors. Large variation between countries in the prevalence of adolescents with four or more risk factors was found in all regions. The country level range was higher in the South-East Asia Region (minimum Sri Lanka = 8%, maximum Myanmar = 84%) than Western Pacific Region (minimum China = 3%, maximum Niue = 72%), European Region (minimum Sweden = 13.9%, maximum Ireland = 66.0%), African Region (minimum Senegal = 0.8%, maximum Uganda = 82.1%) and Eastern Mediterranean Region (minimum Libya = 0.2%, maximum Lebanon = 80.2%). Insufficient vegetable consumption, insufficient fruit consumption and physically inactivity were three of the four most prevalent risk factors in all regions. Interpretation: Our results suggest a high prevalence of four or more NCD risk factors in adolescents globally, although variation was found between countries. Results from our study indicate that efforts to reduce adolescent NCD risk factors and the associated health burden need to be improved. These findings can assist policy makers to target the rollout of country- specific interventions. Funding: None.

Abstract Anisotropy is one factor that appears to be significantly important in the studies of relativistic compact stars. In this paper, we make a generalization of the Buchdahl limit by incorporating an anisotropic effect for a selected class of exact solutions describing anisotropic stellar objects. In the isotropic case of a homogeneous distribution, we regain the Buchdahl limit $$2M/R \le 8/9$$ 2 M / R ≤ 8 / 9 . Our investigation shows a direct link between the maximum allowed compactness and pressure anisotropy vi-a-vis geometry of the associated 3-space.

The efficiency of Aspergillus tamarii (isolated from sludge of a textile industry) was investigated to remediate the synthetic solutions of reactive red 120 (RR120) dye and chromium(III) separately. Also, parallel studies were conducted on the bioremediation of binary system of chromium(III) and RR120 dye in different ratios. The study was conducted to find the potential of the A. tamarii for removing chromium(III) and color from solutions containing only chromium or only RR120 dye or both and the effect of RR120 and chromium on the growth of the strain were observed. Maximum dye removal 81 mg/L was observed from 100 mg/L RR120 dye solution at pH 5 up to 50 hours. Maximum chromium removal 88.3 mg/L was observed from 100 mg/L chromium (III) solution at pH 5 up to 50 hours. In previous studies, A. tamarii was used as a bioremediator for removing different chromium complex dyes. The removal of chromium(III) and color were compared from solutions of synthetic mixtures and chromium complex dyes. The response of bioremediation study was validated using multiple regression analysis.

Identification of the genomic diversity and the phylodynamic profiles of prevalent variants is critical to understand the evolution and spread of SARS-CoV-2 variants. We performed whole-genome sequencing of 54 SARS-CoV-2 variants collected from COVID-19 patients in Kolkata, West Bengal during August–October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad that are available in the GISAID database. We estimated the clade dynamics of the Indian variants and compared the clade-specific mutations and the co-mutation patterns across states and union territories of India over the time course. Frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating the emergence of newer mutations in the viral population prevailing in the country. Furthermore, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested in Indian patients.

Abstract Objectives To evaluate the effect of the combination of hydroxychloroquine (HCQ) and standard personal protective equipment (PPE) compared to the use of standard personal protective equipment alone on the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers(HCWs) in India Trial design HOPE is an investigator initiated multi-centre open-label parallel group randomized controlled trial. Participants All HCWs currently working in an environment with direct exposure to patients with confirmed COVID-19 infection are eligible to participate in the trial. The trial aims to be conducted across 20-30 centres (public and private hospitals) in India. HCWs who decline consent, who have a confirmed COVID-19 infection, those who are already on chloroquine/HCQ for any indication, or if pregnant or breast-feeding, or have known QT prolongation or are on medications that when taken with HCQ can prolong the QTc will be excluded. Intervention and comparator The interventions to be compared in this trial are standard practice (use of recommended PPE) and HCQ plus standard practice. In the standard practice arm, HCWs will use recommended PPE as per institutional guidelines and based on their roles. They will be discouraged from taking HCQ to prevent contamination and contacted every week for the duration of the study to ascertain if they have taken any HCQ. Any such use will be reported as a protocol violation. In the intervention arm, HCWs will be administered 800mg of HCQ as a loading dose on the day of randomization (as two 400mg doses 12hrs apart) and subsequently continued on 400mg once a week for 12 weeks. This will be in addition to the use of recommended PPE as per institutional guidelines and based on their roles. HCWs will collect the drug once every week from designated research and pharmacy staff at site. A weekly phone reminder will be provided to participants in this arm to ensure compliance. An ECG will be performed between 4-6 weeks in this arm and if the QTc is prolonged (greater than 450milliseconds), the drug will be stopped. Follow-up will however continue. Participants in both arms will receive a weekly phone call for evaluation of the primary outcome, to monitor protocol compliance and development of any adverse events (in the HCQ group). Main outcomes Participants will be followed on a weekly basis. The primary outcome is the proportion of HCWs developing laboratory confirmed COVID-19 infection within 6 months of randomization. We will also evaluate a number of secondary outcomes, including hospitalization related to suspected/confirmed COVID-19 infection, intensive care unit or high-dependency unit admission due to suspected/confirmed COVID-19 infection, all-cause mortality, need for organ support ( non-invasive or invasive ventilation, vasopressors and renal replacement therapy), ICU and hospital length of stay, readmission, days off work and treatment-related adverse events. Randomisation Randomisation will be conducted through a password-protected, secure website using a central, computer-based randomisation program. Randomisation will be stratified by participating institutions and by the role of HCW – nursing, medical and other. Participants will be randomised 1:1 to either standard practice only or HCQ plus standard practice. Allocation concealment is maintained by central web-based randomisation Blinding (masking) This is an unblinded study: study assigned treatment will be known to the research team and participant. Bias will be mitigated through an objective end point (laboratory confirmed COVID-19 infection). Numbers to be randomised (sample size) A total of 6,950 HCWs will be enrolled (3475 to the intervention) and (3475 to the standard practice group) to detect a 25% relative reduction, or 2.5% absolute reduction, in the infection rate from an estimated baseline infection rate of 10%, with 80% statistical power using a two-sided test at 5% level of significance. Available data from China and Italy indicate that the rate of infection among frontline healthcare workers varies between 4% to 12%. We therefore assumed a baseline infection rate of 10% among HCWs. This sample size allows for a potential loss to follow-up rate of 10% and a potential non-compliance rate of 10% in both the treatment and control arms. Trial Status HOPE protocol version 3.0 dated June 3rd 2020. Recruitment started on 29th June 2020 and currently 56 participants have been enrolled. Planned completion of enrolment is January 31st 2021. Trial registration Clinical Trials Registry of India: CTRI/2020/05/025067 (prospectively registered) Date of registration: 6th May 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expedited dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Abstract Objective Pabda (Ompok bimaculatus) is a freshwater catfish, largely available in Asian countries, especially in Bangladesh, India, Pakistan and Nepal. This fish is highly valued for its fabulous taste and high nutritional value and is very popular as a rich source of proteins, omega-3 and omega-6 fatty acids, vitamins and mineral for growing children, pregnant females and elders. We performed de-novo sequencing of Ompok bimaculatus using a hybrid approach and present here a draft assembly for this species for the first time. Data Description The genome of Ompok bimaculatus (Fig. 1: Table 1, Data file 3) from Ganges river, has been sequenced by hybrid approach using Illumina short reads and PacBio long reads followed by structural annotations. The draft genome assembly was found to be 718 Mb with N50 size of 81 kb. MAKER gene annotation tool predicted 21,371 genes.

Introduction: High prevalence of chronic kidney disease (CKD) not associated with known risk factors has been reported from coastal districts of Andhra Pradesh. The Study to Test and Operationalize Preventive Approaches for Chronic Kidney Disease of Undetermined Etiology in Andhra Pradesh (STOP CKDu AP) aims to ascertain the burden (prevalence and incidence) of CKD, the risk factor profile, and the community perceptions about the disease in the Uddanam area of Andhra Pradesh. Methods: Study participants will be sampled from the Uddanam area using multistage cluster random sampling. Information will be collected on the demographic profile, occupational history, and presence of conventional as well as nonconventional risk factors. Glomerular filtration rate (GFR) will be estimated using the Chronic Kidney Disease Epidemiology Collaboration equation, and proteinuria will be measured. All abnormal values will be confirmed by repeat testing after 3 months. Cases of CKD not associated with identified etiologies will be identified. Biospecimens will be stored to explore future hypotheses. The entire cohort will be followed up every 6 months to determine the incidence of CKD and to identify risk factors for decline in kidney function. Qualitative studies will be performed to understand the community perceptions and expectations with respect to the interventions. Implications: CKD is an important public health challenge in low- and middle-income countries. This study will establish the prevalence and determine the incidence of CKD not associated with known risk factors in a reported high-burden region, and will provide insights to help design targeted health systems responses. The findings will contribute to the policy development to tackle CKD in the region and will permit international comparisons with other regions with similar high prevalence. Keywords: chronic kidney disease, CKD of uncertain etiology, risk factors

BackgroundGlobal cardiovascular disease (CVD) burden is high and rising, especially in low-income and middle-income countries (LMICs). Focussing on 45 LMICs, we aimed to determine (1) the adult population's median 10-year predicted CVD risk, including its variation within countries by socio-demographic characteristics, and (2) the prevalence of self-reported blood pressure (BP) medication use among those with and without an indication for such medication as per World Health Organization (WHO) guidelines.Methods and findingsWe conducted a cross-sectional analysis of nationally representative household surveys from 45 LMICs carried out between 2005 and 2017, with 32 surveys being WHO Stepwise Approach to Surveillance (STEPS) surveys. Country-specific median 10-year CVD risk was calculated using the 2019 WHO CVD Risk Chart Working Group non-laboratory-based equations. BP medication indications were based on the WHO Package of Essential Noncommunicable Disease Interventions guidelines. Regression models examined associations between CVD risk, BP medication use, and socio-demographic characteristics. Our complete case analysis included 600,484 adults from 45 countries. Median 10-year CVD risk (interquartile range [IQR]) for males and females was 2.7% (2.3%-4.2%) and 1.6% (1.3%-2.1%), respectively, with estimates indicating the lowest risk in sub-Saharan Africa and highest in Europe and the Eastern Mediterranean. Higher educational attainment and current employment were associated with lower CVD risk in most countries. Of those indicated for BP medication, the median (IQR) percentage taking medication was 24.2% (15.4%-37.2%) for males and 41.6% (23.9%-53.8%) for females. Conversely, a median (IQR) 47.1% (36.1%-58.6%) of all people taking a BP medication were not indicated for such based on CVD risk status. There was no association between BP medication use and socio-demographic characteristics in most of the 45 study countries. Study limitations include variation in country survey methods, most notably the sample age range and year of data collection, insufficient data to use the laboratory-based CVD risk equations, and an inability to determine past history of a CVD diagnosis.ConclusionsThis study found underuse of guideline-indicated BP medication in people with elevated CVD risk and overuse by people with lower CVD risk. Country-specific targeted policies are needed to help improve the identification and management of those at highest CVD risk.

Transition planning is the foundation for addressing post-secondary goals leading to improved outcomes. Transition assessments guide the transition planning process. Given the importance of transition assessment results, practitioners need access to measures supporting the active involvement of youth with intellectual disability. One such method is the occupational interests card sort. This study investigated the use of an occupational interests card sort with youth with intellectual disability, assessing its impact on their career decision self-efficacy. Results indicated that the occupational interests card sort influenced young adults’ ability to select career goals, as well as identify career themes beyond occupational interests.

Abstract Background To improve immunization coverage, most interventions that are part of the national immunization program in India address supply-side challenges. But, there is growing evidence that addressing demand-side factors can potentially contribute to improvement in childhood vaccination coverage in low- and middle-income countries. Participatory engagement of communities can address demand-side barriers while also mobilizing the community to advocate for better service delivery. The objective of this study is to evaluate the impact of a novel community engagement approach in improving immunization coverage. In our proposed intervention, we go a step beyond merely engaging the community and strive towards increasing ‘ownership’ by the communities. Methods/Design We adopt a cluster randomized design with two groups to evaluate the intervention in Assam, a state in the northeast region of India. To recruit villages and participants at baseline, we used a two-stage stratified random sampling method. We stratified villages; our unit of randomization, based on census data and randomly selected villages from each of the four strata. At the second-stage, we selected random sub-sample of eligible households (having children in the age group of 6–23 months) from each selected village. The study uses a repeated cross sectional design where we track the same sampled villages but draw independent random samples of households at baseline and endline. Total number of villages required for the study is 180 with 15 eligible HHs from each village. Post-baseline survey, we adopt a stratified randomization strategy to achieve better balance in intervention and control groups, leveraging information from the extensive baseline survey. Discussion The proposed intervention can help identify barriers to vaccination at the local level and potentially lead to more sustainable solutions over the long term. Our sampling design, sample size calculation, and randomization strategy address internal validity of our evaluation design. We believe that it would allow us to causally relate any observed changes in immunization coverage to the intervention. Trial registration The trial has been registered on 7th February, 2017 under the Clinical Trials Registry- India (CTRI), hosted at the ICMR’s National Institute of Medical Statistics, having registration number CTRI/2017/02/007792. This is the original study protocol.

A notion of pi-tolerant equilibrium is defined that takes into account that players have some tolerance regarding payoffs in a game. This solution concept generalizes Nash and refines epsilon-Nash equilibrium in a natural way. We show that pi-tolerant equilibrium can explain cooperation in social dilemmas such as Prisoner's Dilemma and the Public Good game. We then examine the structure of particularly cooperative pi-tolerant equilibria, where players are as cooperative as they can be, subject to their tolerances, in Prisoner's Dilemma. To the extent that cooperation is due to tolerance, these results provide guidance to a mechanism designer who has some control over the payoffs in a game, and suggest ways in which cooperation can be increased.

MicroRNAs are a newly discovered class of non-protein small RNAs with 22–24 nucleotides. They play multiple roles in biological processes including development, cell proliferation, apoptosis, stress responses and many other cell functions. In this research, several approaches were combined to make a computational prediction of potential miRNAs and their targets in Helianthus annuus (H. annuus). The already available information of the plant miRNAs present in miRBase v21 was used against expressed sequence tags (ESTs). A total of three miRNAs were detected from which one potential novel miRNA was identified following a range of strict filtering criteria. The target prediction was carried out for these three miRNAs having various targets. These targets were functionally annotated and GO terms were assigned. To study the conserved nature of the miRNAs, predicted phylogenetic analysis was carried out. These findings will significantly provide the broader picture for understanding the functions in H. annuus.

The effects of methyl jasmonate (MeJA), an elicitor of plant defense mechanisms, on the biosynthesis of diosgenin, a steroidal saponin, were investigated in six fenugreek (Trigonella foenum-graecum) varieties (Gujarat Methi-2, Kasuri-1, Kasuri-2, Pusa Early Branching, Rajasthan Methi and Maharashtra Methi-5). Treatment with 0.01% MeJA increased diosgenin levels, in 12 days old seedlings, from 0.5%–0.9% to 1.1%–1.8%. In addition, MeJA upregulated the expression of two pivotal genes of the mevalonate pathway, the metabolic route leading to diosgenin: 3-hydroxy-3-methylglutaryl-CoA reductase (HMG) and sterol-3-β-glucosyl transferase (STRL). In particular, MeJA increased the expression of HMG and STRL genes by 3.2- and 22.2-fold, respectively, in the Gujarat Methi-2 variety, and by 25.4- and 28.4-fold, respectively, in the Kasuri-2 variety. Therefore, MeJA may be considered a promising elicitor for diosgenin production by fenugreek plants.

Background: Studying drug use pattern among medical practitioners is of vital importance due to use of irrational drugs. Objective: This observational descriptive cross sectional study was carried out to assess prescribing practice in the out-patient department of Block Rural Hospital of West Bengal. Methods: By systematic random sampling technique total 160 prescriptions from all the prescribing recommendations of the out-patient department of the block rural hospital were studied. The data were collected by scrutinizing individual prescription of the eligible participants using predesigned, pretested schedule study tool during the study period of two months. The prescriptions were analyzed in the context of correctness of components of instructions and adherence to WHO core prescribing indicators. Results: Overall, an average number of drugs per prescription were 3.01±0.02. Only 155(32.22%) out of the total 481 drugs were prescribed by generic names. Among prescriptions antibiotics were in 71.87 percent and injectable preparations in 11.87 percent; 91.06 percent drugs were prescribed from national list of Essential Medicines of India. In terms of correctness, content of the drugs prescribed, was unacceptable; adherence to WHO core prescribing indicators was poor. Conclusion: Our study revealed that we need to identify loopholes regarding practices to improve the standard of prescriptions.

T L. (fenugreek) is a viable alternative for production of diosgenin because of its shorter growing cycle, lower production costs, and consistent yield and quality. We studied de novo transcriptome analysis along with the diosgenin pathway in and identified the genes responsible for diosgenin biosynthesis. The GMV-1 variety of has been used in the present study for transcriptome analysis by sequencing messenger ribonucleic acid (RNA) with a SOLiD 4 Genome Analyzer. Deep sequencing data of the transcriptome was assembled using various assembly tools along with functional annotation of genes, and pathway analysis for diosgenin biosynthesis was deciphered. A total of 42 million high quality reads were obtained. De novo assembly was performed using Velvet at different -mer, Oases, and CLC Genomics Workbench, which generated 20,561 transcript contigs. CAP3 was used to reduce the redundancy of contigs obtained through these assemblers. A total of 18,333 transcript contigs were functionally annotated. Kyoto Encyclopedia of Genes and Genomes pathway mapping showed that 6775 transcripts were related to plant biochemical pathways including the diosgenin biosynthesis pathway. The large number of transcripts reported in the current study will serve as a valuable genetic resource for Sequence information of the genes that were involved in diosgenin biosynthesis could be used for metabolic engineering of to increase diosgenin content.

Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays.Replicate enrollment serum aliquots from 388 unvaccinated women in the control arm of the Costa Rica HPV vaccine trial were measured for HPV16 seropositivity using three serological assays: a VLP-based direct ELISA; a VLP-based competitive Luminex immunoassay (cLIA); and a secreted alkaline phosphatase protein neutralization assay (SEAP-NA). We assessed the association of assay seropositivity and risk of subsequent HPV16 infection over four years of follow-up by calculating sampling-adjusted odds ratios (OR) and HPV16 seropositivity based on standard cutoff from the cLIA was significantly associated with protection from subsequent HPV16 infection (OR = 0.48, CI = 0.27-0.86, compared with seronegatives). Compared with seronegatives, the highest seropositive tertile antibody levels from the direct ELISA (OR = 0.53, CI = 0.28-0.90) as well as the SEAP-NA (OR = 0.20, CI = 0.06, 0.64) were also significantly associated with protection from HPV16 infection.Enrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, although cutoffs for immune protection were different. We defined the assays and seropositivity levels after natural infection that better measure and translate to protective immunity.

Identification of the genomic diversity and the phylodynamic profiles of prevalent variants is critical to understand the evolution and spread of SARS-CoV-2 variants. We performed whole-genome sequencing of 54 SARS-CoV-2 variants collected from COVID-19 patients in Kolkata, West Bengal during August–October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad that are available in the GISAID database. We estimated the clade dynamics of the Indian variants and compared the clade-specific mutations and the co-mutation patterns across states and union territories of India over the time course. Frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating the emergence of newer mutations in the viral population prevailing in the country. Furthermore, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested in Indian patients. [ABSTRACT FROM AUTHOR]