An insight into the prokaryotic diversity from a polymetallic nodule-rich region in the Central Indian Ocean Basin using next generation sequencing approach.

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.

Centre-level variation in the survival of patients receiving haemodialysis in India: findings from a nationwide private haemodialysis network.

Background: There are no large studies examining survival in patients receiving haemodialysis in India or considering centre-level effects on survival. We measured survival variation between dialysis centres across India and evaluated the extent to which differences are explained by measured centre characteristics. Methods: This is a multilevel analysis of patient survival in centres of the NephroPlus dialysis network consisting of 193 centres across India. Patients receiving haemodialysis at a centre for ≥90 days between April 2014 and June 2019 were included, with analyses restricted to centres with ≥10 such patients. The primary outcome was all-cause mortality, measured from 90 days after joining a centre. Proportional hazards models with shared frailty were used to model centre- and patient-level effects on survival. Findings: Amongst 23,601 patients (median age 53 years; 29% female), the unadjusted centre-specific 180-day Kaplan-Meier survival estimates ranged between 55% (95% confidence interval [CI] 38-80%) and 100%, with a median of 88% (interquartile interval 83%-92%). After accounting for multilevel factors, estimated 180-day survival ranged between 83% (73-89%) and 97% (95-98%), with 90% 180-day survival in the average centre. The mortality rate in patients attending rural centres was 32% (Hazard Ratio 1.32; 95% CI 1.06-1.65) higher than those at urban centres in adjusted analyses. Multiple patient characteristics were associated with mortality. Interpretation: This is the first national benchmark for survival amongst dialysis patients in India. Centre- and patient-level characteristics are associated with survival but there remains unexplained variation between centres. As India continues to widen dialysis access, ongoing quality improvement programs will be an important part of ensuring that patients experience the best possible outcomes at the point of care. Funding: This project received no external funding.

The association of hypertension among married Indian couples: a nationally representative cross-sectional study.

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: 18-49y, men: 21-54y) who participated in the National Family Health Survey-V (2019-21). 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.

Multi-objective optimization of ternary blends of Algal biodiesel-diesel-1-decanol to mitigate environmental pollution in powering a diesel engine using RSM, ANOVA, and artificial bee colony.

This research presents an in-depth examination that utilizes a hybrid technique consisting of response surface methodology (RSM) for experimental design, analysis of variance (ANOVA) for model development, and the artificial bee colony (ABC) algorithm for multi-objective optimization. The study aims to enhance engine performance and reduce emissions through the integration of global maxima for brake thermal efficiency (BTE) and global minima for brake-specific fuel consumption (BSFC), hydrocarbon (HC), nitrogen oxides (NOx), and carbon monoxide (CO) emissions into a composite objective function. The relative importance of each objective was determined using weighted combinations. The ABC algorithm effectively explored the parameter space, determining the optimum values for brake mean effective pressure (BMEP) and 1-decanol% in the fuel mix. The results showed that the optimized solution, with a BMEP of 4.91 and a 1-decanol % of 9.82, improved engine performance and cut emissions significantly. Notably, the BSFC was reduced to 0.29 kg/kWh, demonstrating energy efficiency. CO emissions were lowered to 0.598 vol.%, NOx emissions to 1509.91 ppm, and HC emissions to 29.52 vol.%. Furthermore, the optimizing procedure produced an astounding brake thermal efficiency (BTE) of 28.78%, indicating better thermal energy efficiency within the engine. The ABC algorithm enhanced engine performance and lowered emissions overall, highlighting the advantageous trade-offs made by a weighted mix of objectives. The study's findings contribute to more sustainable combustion engine practises by providing crucial insights for upgrading engines with higher efficiency and fewer emissions, thus furthering renewable energy aspirations.

Estimating excess mortality due to female genital mutilation.

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 [Formula: see text]-[Formula: see text]). 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.

Hope, proactive personality, coping styles, and satisfaction with life among veterans during COVID-19.

Veterans of the U.S. Armed Forces are an at-risk population given their increased mental health concerns resulting from their military service. However, there has been limited research conducted with this population during the novel coronavirus (COVID-19) pandemic. The purpose of this exploratory study was to examine aspects of positive psychological functioning with 132 U.S. veterans during COVID-19 using Lazarus and Folkman's (1984) transactional model of stress and coping. Specifically, we examined the personal resources of hope and proactive personality, two coping styles, and satisfaction with life. We performed correlation analyses to determine how these constructs related to each other. We also conducted a regression analysis to examine if the two dimensions of hope, proactive personality, adaptive coping, and maladaptive coping predicted veterans' satisfaction with life. Lastly, we utilized a mediation analysis to investigate whether two coping styles mediated the relationships among personal resources and satisfaction with life. Findings from the regression analysis suggested hope pathways and proactive personality were significant predictors of satisfaction with life. Results from the mediation analysis suggested that adaptive and maladaptive coping did not mediate the relationships among personal resources and satisfaction with life.

Identification of G-quadruplex structures in MALAT1 lncRNA that interact with nucleolin and nucleophosmin.

Nuclear-retained long non-coding RNAs (lncRNAs) including MALAT1 have emerged as critical regulators of many molecular processes including transcription, alternative splicing and chromatin organization. Here, we report the presence of three conserved and thermodynamically stable RNA G-quadruplexes (rG4s) located in the 3' region of MALAT1. Using rG4 domain-specific RNA pull-down followed by mass spectrometry and RNA immunoprecipitation, we demonstrated that the MALAT1 rG4 structures are specifically bound by two nucleolar proteins, Nucleolin (NCL) and Nucleophosmin (NPM). Using imaging, we found that the MALAT1 rG4s facilitate the localization of both NCL and NPM to nuclear speckles, and specific G-to-A mutations that disrupt the rG4 structures compromised the localization of both NCL and NPM in speckles. In vitro biophysical studies established that a truncated version of NCL (ΔNCL) binds tightly to all three rG4s. Overall, our study revealed new rG4s within MALAT1, established that they are specifically recognized by NCL and NPM, and showed that disrupting the rG4s abolished localization of these proteins to nuclear speckles.

Frailty among middle-aged and older women and men in India: findings from wave 1 of the longitudinal Ageing study in India.

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.

Clustering of metabolic and behavioural risk factors for cardiovascular diseases among the adult population in South and Southeast Asia: findings from WHO STEPS data.

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.

Impact of leachate and landfill gas on the ecosystem and health: Research trends and the way forward towards sustainability.

Globally, a whopping increase in solid waste (SW) generation and the risks posed by climate change are major concerns. A wide spread practice for disposal of municipal solid waste (MSW) is landfill, which swells with population and urbanization. Waste, if treated properly, can be used to produce renewable energy. The recent global event COP 27 mainly stressed on production of renewable energy to achieve the Net Zero target. The MSW landfill is the most significant anthropogenic source of methane (CH4) emission. On one side, CH4 is a greenhouse gas (GHG), and on the other it is a main component of biogas. Wastewater that collects due to rainwater percolation in landfills creates landfill leachate. There is a need to understand global landfill management practices thoroughly for implementation of better practices and policies related to this threat. This study critically reviews recent publications on leachate and landfill gas. The review discusses leachate treatment and landfill gas emissions, focusing on the possible reduction technology of CH4 emission and its impact on the environment. Mixed leachate will benefit from the combinational therapy method because of its intricate combination. Implementation of circular material management, entrepreneurship ideas, blockchain, machine learning, LCA usage in waste management, and economic benefits from CH4 production have been emphasized. Bibliometric analysis of 908 articles from the last 37 years revealed that industrialized nations dominate this research domain, with the United States having the highest number of citations.

Landscape assessment of the cities in the state of Maharashtra: first step towards air quality management (AQM) and strategic implementation of mitigation plans.

OBJECTIVE OF THE STUDY: This study aims to understand the need for landscape assessment of the 18 non-attainment cities in the state of Maharashtra, to understand and rank the cities according to the need and necessity for strategic implementation of air quality management. This air quality management is a National Clean Air Programme initiative to curb the air pollution level in all the highly polluted Indian cities by 20-30% till 2024. METHODOLOGY: The ranking and selection of the cities consisted of a two-phase approach including (a) desk research and (b) field interventions and stakeholders' consultations. The first phase included (ai) review of 18 non-attainment cities in Maharashtra, (aii) identification of suitable indicators to inform prioritisation during the ranking process, (aiii) data collection and analysis of the indicators and (aiv) the ranking of the 18 non-attainment cities in Maharashtra. The second phase, i.e. field interventions included (bi) Mapping of stakeholders and field visits, (bii) the consultations with the stakeholders, (biii) information and data collection and (biv) ranking and selection of cities. On analysing the score obtained from both the approaches a ranking of all the cities is done accordingly. RESULTS AND DISCUSSION: The screening of cities from the first phase gave a possible list of 8 cities-Aurangabad, Kolhapur, Mumbai, Nagpur, Nashik, Navi Mumbai, Pune, Solapur. Further, the second round of analysis involving field interventions and stakeholder consultations was done within the 8 cities to find out the most suitable list of two to 5 cities. The second research analysis gave Aurangabad, Kolhapur, Mumbai, Navi Mumbai and Pune. A more granular stakeholder consultation resulted in the selection of cities like Navi Mumbai and Pune as the cities where implementation of new strategies seemed feasible. INTERVENTION AND ACTIVITIES: New strategic interventions like (a) strengthen the clean air ecosystem/institutions, (b) air quality monitoring and health impact assessment, and (c) skill development to ensure the long-term sustainability of initiatives planned for the cities.

Sex differences in non-communicable disease multimorbidity among adults aged 45 years or older in India.

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.

A randomized trial of once daily versus twice daily dosing of oral iron in CKD.

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 (ß = - 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 (ß = - 0.36, 95% CI - 0.61 to - 0.10) whereas MCHC increased in the OD group as compared to decrease in the BD group (ß = 0.37, 95% CI 0.067-0.67). These observations need exploration to ascertain the impact of different oral iron dosing strategies in CKD.

Patterns of multimorbidity among a community-based cohort in rural India.

Background: Multimorbidity estimates are expected to increase in India primarily due to the population aging. However, there is a lack of research estimating the burden of multimorbidity in the Indian context using a validated tool. We estimated the prevalence and determinants of multimorbidity amongst the adult population of the rural Uddanam region, Andhra Pradesh. Methods: This community-based cross-sectional study was conducted as a part of an ongoing research program. Multistage cluster sampling technique was used to select 2419 adult participants from 40 clusters. Multimorbidity was assessed using Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC) tool, collecting information on 13 chronic diseases. Patient Health Questionnaire (PHQ-12) was used to screen for depression. Multiple logistic regression was conducted to identify the strongest determinants of multimorbidity. Results: Of the 2419 participants, 2289 completed the MAQ-PC tool. Mean age (standard deviation) of participants was 48.1 (13.1) years. The overall prevalence of multimorbidity was 58.5% (95% CI 56.5-60.6); with 30.7%, 15.6%, and 12.2% reporting two, three, and four chronic conditions, respectively. Acid peptic disease-musculoskeletal disease (44%) and acid peptic disease-musculoskeletal disease-hypertension (14.9%) were the most common dyad and triad. Among metabolic diseases, diabetes-hypertension (28.3%) and diabetes-hypertension-chronic kidney disease (7.6%) were the most common dyad and triad, respectively. Advancing age, female gender, and being obese were the strongest determinates of the presence of multimorbidity. Depression was highly prevalent among the study population, and participants with higher PHQ-12 score had 3.7 (2.5-5.4) greater odds of having multimorbidity. Conclusions: Our findings suggest that six of 10 adults in rural India are affected with multimorbidity. We report a higher prevalence of multimorbidity as compared with other studies conducted in India. We also identified vulnerable groups which would guide policy makers in developing holistic care packages for individuals with multimorbidity.

Measurement invariance of the Mental Health Continuum-Short Form across US military veteran and civilian adults.

OBJECTIVE: Recent research has suggested that mental health is not only the absence of mental illness but includes aspects of well-being. One common psychological assessment used to assess dimensions of well-being is the Mental Health Continuum-Short Form (MHC-SF). The MHC-SF is a 14-item measure that assesses emotional, psychological, and social well-being. The purpose of this study was to assess measurement invariance of the MHC-SF across US military veterans and civilians. METHOD: First, we examined the factor structure of the MHC-SF separately for veterans (n = 418) and civilians (n = 411). We then conducted multiple group confirmatory factor analysis (MG-CFA) to assess measurement invariance for the two groups. RESULTS: Findings suggested there were three latent factors representing emotional, social, and psychological well-being. Results from MG-CFA suggested that the MHC-SF is invariant across veterans and civilians. CONCLUSION: Researchers and practitioners can administer the MHC-SF with both groups.

Carbonyl Profiles of Electronic Nicotine Delivery System (ENDS) Aerosols Reflect Both the Chemical Composition and the Numbers of E-Liquid Ingredients-Focus on the In Vitro Toxicity of Strawberry and Vanilla Flavors.

Propylene glycol (PG) and glycerin (G) are the most widely used humectants in electronic nicotine delivery system (ENDS) devices. Carbonyls are present in aerosols produced when ENDS devices heat PG and G. Whether aerosolized PG and G are innocuous to the lungs has not been established. Here, we determined the chemical profiles of ENDS aerosols containing three humectant ratios (30/70, 50/50 and 70/30, PG/VG), for three flavors (strawberry, vanilla and Catalan cream) containing either 12 or 18 mg/mL of nicotine. Additionally, we examined the in vitro toxicity of the strawberry- and vanilla-flavored ENDS aerosol in human lung epithelial cells (BEAS-2B) exposed at the air-liquid interface for 1 h. For strawberry- and vanilla-flavored aerosols produced by a 3rd-generation ENDS device with the same PG/G ratio, the e-liquid nicotine content of 12 and 18 mg/mL did not transfer to the aerosol with substantial differences in concentrations. Our data also indicate the presence of carbonyls in all three flavored e-cig aerosols analyzed, with levels exceeding 1 µg/puff for acetone, butyraldehyde, and acetaldehyde, in strawberry-, vanilla, and Catalan cream-flavored e-cig aerosols, respectively. Furthermore, closed-system ENDS of the fourth generation emitted trace levels of carbonyls in the aerosols (<0.3 µg/puff), while open-system tank-style ENDS of the third generation produced elevated levels of harmful chemicals, including acrolein (>1 µg/puff), formaldehyde (>5 µg/puff), and m- & p-tolualdehyde (>4 µg/puff). Moreover, under non-cytotoxic conditions, BEAS-2B cells exposed to strawberry-flavored aerosols exhibited significantly increased reactive oxygen and nitric oxide species (ROS/NOS) levels in cell media compared to air controls, while vanilla-flavored ENDS aerosols up-regulated the expression of pro-inflammatory and oxidative stress markers. Our data suggest (a) that ENDS aerosol chemical composition will vary based upon the presence and concentration of the initial e-liquid ingredients, with a pronounced impact of the flavoring components; and (b) short-term exposures to flavored ENDS aerosols may impair lung cells' redox signaling in a flavor-specific manner.

Serum myo-inositol oxygenase levels at hospital discharge predict progression to chronic kidney disease in community-acquired acute kidney injury.

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 < 60 ml/min/1.73 m2 or dialysis dependence at 4 month after discharge, were analyzed using multivariate logistic regression analysis and penalized least absolute shrinkage and selection operator logistic regression. Out of a total 126 patients followed up for 4 months, 25 developed CKD. Those who developed CKD were older (p = 0.008), had higher serum creatinine (p < 0.001) and lower serum albumin (p = 0.001) at discharge. Adjusted logistic regression showed that each 10% increase in standardized serum myo-inositol oxygenase (MIOX) level increased the odds of progression to CKD by 13.5%. With 10% increase in standardized urine Neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine and urine protein creatinine ratio (uPCR), increase in the odds of progression to CKD was 10.5%, 9.6% and 8%, respectively. Multivariable logistic model including serum MIOX, discharge serum creatinine and discharge uPCR, was able to predict the progression of CKD [AUC ROC 0.88; (95% CI 0.81, 0.95)]. High level serum MIOX levels at the time of discharge from hospital are associated with progression to CKD in patients with CA-AKI.

Prevalence of multiple non-communicable diseases risk factors among adolescents in 140 countries: A population-based study.

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.

Hepatitis B Virus-Encoded HBsAg Contributes to Hepatocarcinogenesis by Inducing the Oncogenic Long Noncoding RNA LINC00665 through the NF-κB Pathway.

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.

Multimorbidity matters in low and middle-income countries.

Multimorbidity is a complex challenge affecting individuals, families, caregivers, and health systems worldwide. The burden of multimorbidity is remarkable in low- and middle-income countries (LMICs) given the many existing challenges in these settings. Investigating multimorbidity in LMICs poses many challenges including the different conditions studied, and the restriction of data sources to relatively few countries, limiting comparability and representativeness. This has led to a paucity of evidence on multimorbidity prevalence and trends, disease clusters, and health outcomes, particularly longitudinal outcomes. In this paper, based on our experience of investigating multimorbidity in LMICs contexts, we discuss how the structure of the health system does not favor addressing multimorbidity, and how this is amplified by social and economic disparities and, more recently, by the COVID-19 pandemic. We argue that generating epidemiologic data around multimorbidity with similar methods and definition is essential to improve comparability, guide clinical decision-making and inform policies, research priorities, and local responses. We call for action on policy to refinance and prioritize primary care and integrated care as the center of multimorbidity.