MicroRNA-29b-3p degenerates terminally differentiated dopaminergic SH-SY5Y cells by perturbation of mitochondrial functions.

Mitochondrial dysfunction is the main cause of gradual deterioration of structure and function of neuronal cells, eventually resulting in neurodegeneration. Studies have revealed a complex interrelationship between neurotoxicant exposure, mitochondrial dysfunction, and neurodegenerative diseases. Alteration in the expression of microRNAs (miRNAs) has also been linked with disruption in mitochondrial homeostasis and bioenergetics. In our recent research (Cellular and Molecular Neurobiology (2023) https://doi.org/10.1007/s10571-023-01362-4), we have identified miR-29b-3p as one of the most significantly up-regulated miRNAs in the blood of Parkinson's patients. The findings of the present study revealed that neurotoxicants of two different natures, that is, arsenic or rotenone, dramatically increased miR-29b-3p expression (18.63-fold and 12.85-fold, respectively) in differentiated dopaminergic SH-SY5Y cells. This dysregulation of miR-29b-3p intricately modulated mitochondrial morphology, induced oxidative stress, and perturbed mitochondrial membrane potential, collectively contributing to the degeneration of dopaminergic cells. Additionally, using assays for mitochondrial bioenergetics in live and differentiated SH-SY5Y cells, a reduction in oxygen consumption rate (OCR), maximal respiration, basal respiration, and non-mitochondrial respiration was observed in cells transfected with mimics of miR-29b-3p. Inhibition of miR-29b-3p by transfecting inhibitor of miR-29b-3p prior to exposure to neurotoxicants significantly restored OCR and other respiration parameters. Furthermore, we observed that induction of miR-29b-3p activates neuronal apoptosis via sirtuin-1(SIRT-1)/YinYang-1(YY-1)/peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α)-regulated Bcl-2 interacting protein 3-like-dependent mechanism. Collectively, our studies have shown the role of miR-29b-3p in dysregulation of mitochondrial bioenergetics during degeneration of dopaminergic neurons via regulating SIRT-1/YY-1/PGC-1α axis.

Examining birth preparedness and complication readiness: a systematic review and meta-analysis of pregnant and recently delivered women in India.

BACKGROUND: Birth preparedness and complication readiness (BPCR) is an essential component of safe motherhood programs. This study aims to systematically identify and synthesize available evidence on birth preparedness and complication readiness among pregnant and recently delivered women in India. METHODS: The study followed PRISMA guidelines and used databases such as PubMed, Cochrane Library, and ProQuest. Joanna Briggs Institute [JBI] Tool was used for critical appraisal of studies. The meta-analysis was conducted using Comprehensive Meta-Analysis [CMA] tool and R studio software. Statistical heterogeneity was evaluated using visual inspection of the forest plot, Cochran's Q test, and the I2 statistic results. Funnel plot and Egger's tests were applied to explore the possibility of the publication bias in the studies [PROSPERO: CRD42023396109]. RESULT: Thirty-five cross-sectional studies reported knowledge on one or more components of birth preparedness [BP], whilst knowledge on complication readiness [CR] or danger signs was reported in 34 included studies. Utilizing the random effect model, the pooled result showed that only about half of the women [49%; 95% CI: 44%, 53%] were aware on BPCR components. This result ranged between 15% [95% CI: 12%, 19%] to 79% [95% CI: 72%, 84%] in Maharashtra and Karnataka respectively [I2 = 94%, p = < 0.01]. High heterogeneity [> 90%] is observed across all components [p < 0.01]. The result of subgroup analysis indicated no significant difference in the proportion on BPCR among pregnant women [50%; 95% CI: 45%, 55%] and recently delivered women [54%; 95% CI: 46%, 62%]. However, the southern region of India indicates relatively better [56%; 95% CI: 45%, 67%] prevalence. CONCLUSION: Our study highlights the low prevalence of BPCR in India and the factors associated with it. Scaling up cost-effective interventions like BPCR that have a positive overall effect is necessary. Authors strongly suggests that birth preparedness and complication readiness should be given utmost importance to reduce maternal morbidity and mortality to achieve the Sustainable Development Goals. Consideration should be given to fortifying existing resources, such as frontline workers and primary healthcare, as a strategic approach to augmenting the effectiveness of awareness initiatives.

Ageing at Molecular Level: Role of MicroRNAs.

The progression of age triggers a vast number of diseases including cardiovascular, cancer, and neurodegenerative disorders. Regardless of our plentiful knowledge about age-related diseases, little is understood about molecular pathways that associate the ageing process with various diseases. Several cellular events like senescence, telomere dysfunction, alterations in protein processing, and regulation of gene expression are common between ageing and associated diseases. Accumulating information on the role of microRNAs (miRNAs) suggests targeting miRNAs can aid our understanding of the interplay between ageing and associated diseases. In the present chapter, we have attempted to explore the information available on the role of miRNAs in ageing of various tissues/organs and diseases and understand the molecular mechanism of ageing.

Identifying risk of death in children hospitalized with community-acquired pneumonia.

Objective: To externally validate a tool developed by the Pneumonia Research Partnership to Assess WHO Recommendations study group for identification of the risk of death in children hospitalized with community-acquired pneumonia, the PREPARE tool. Methods: We did a secondary analysis of data collected during hospital-based surveillance of children with community-acquired pneumonia in northern India from January 2015 to February 2022. We included children aged 2-59 months with pulse oximetry assessment. We used multivariable backward stepwise logistic regression analysis to assess the strength of association of the PREPARE variables (except hypothermia) with pneumonia-related death. We estimated sensitivity, specificity, and positive and negative likelihood ratios of the PREPARE score at cut-off scores ≥ 3, ≥ 4 and ≥ 5. Findings: Of 10 943 children screened, 6745 (61.6%) were included in our analysis, of whom 93 (1.4%) died. Age of < 1 year, female sex, weight-for-age < -3 standard deviations, respiratory rate of ≥ 20 breaths/min higher than the age-specific cut-off, and lethargy, convulsions, cyanosis and blood oxygen saturation < 90% were associated with death. In the validation, the PREPARE score had the highest sensitivity (79.6%) with concurrent highest specificity (72.5%) to identify hospitalized children at risk of death from community-acquired pneumonia at a cut-off score of ≥ 5. Area under curve was 0.82 (95% confidence interval: 0.77-0.86). Conclusion: The PREPARE tool with pulse oximetry showed good discriminatory ability on external validation in northern India. The tool can be used to assess risk of death of hospitalized children aged 2-59 months with community-acquired pneumonia for early referral to higher-level facilities.

Transcriptomics and Proteomics Approach for the Identification of Altered Blood microRNAs and Plasma Proteins in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by the selective destruction of dopaminergic neurons (DA-nergic). Clinically, PD is diagnosed based on developing signs and symptoms. A neurological and physical examination and sometimes medical and family history also help in the diagnosis of PD. However, most of these features are visible when more than 80% of the dopaminergic neurons have degenerated. An understanding of the selective degeneration process at the cellular and molecular level and the development of new biomarkers are required for effective PD management. Several studies have been carried out using a selected set of miRNAs/ mRNAs and proteins to develop biomarkers of PD; however, an unbiased and combined miRNA-protein profiling study was required to identify the markers of progressive and selected degeneration of dopaminergic neurons in PD patients. In the present study, we have carried out global protein profiling through LC-MS/MS and miRNA profiling by using a "brain-specific" miRNA array panel of 112 miRNAs in PD patients and healthy controls to find the unprejudiced group of proteins and miRNAs that are deregulating in PD. In the whole blood samples of PD patients compared to healthy controls, the expression of 23 miRNAs and 289 proteins was significantly increased, whereas the expression of 4 miRNAs and 132 proteins was considerably downregulated. Network analysis, functional enrichment, annotation, and analysis of miRNA-protein interactions were also performed as part of the bioinformatics investigation of the discovered miRNAs and proteins revealing several pathways that lead to PD development and pathogenesis. Based on the analysis of miRNA and protein profiling, we have identified four miRNAs (hsa-miR-186-5p, miR-29b, miR-139 & has-miR-150-5p) and four proteins (YWHAZ, PSMA4, HYOU1, & SERPINA1), which can be targeted for the development of new biomarkers of PD. In vitro studies have identified the role of miR-186-5p in regulating the levels of the YWHAZ/YWHAB & CALM2 gene, which has shown maximum downregulation in PD patients and is known for its role in neuroprotection from apoptotic cell death & calcium regulation. In conclusion, our research has identified a group of miRNA-proteins that can be developed as PD biomarkers; however, future studies on the release of these miRNAs and proteins in extracellular vesicles circulating in the blood of PD patients can further validate these as specific biomarkers of PD.

Alarming Trends of Cesarean Section-Time to Rethink: Evidence From a Large-Scale Cross-sectional Sample Survey in India.

BACKGROUND: Cesarean section (CS) delivery rate has increased significantly both globally and in India, thereby posing a burden on overstretched health systems. OBJECTIVE: This study plans to understand the factors associated with CS rate with an objective to (1) analyze the trends of CS delivery from 1998-99 to 2019-21 and (2) understand the proximate determinants of CS deliveries in India. METHODS: Analysis of secondary data (National Family Health Survey) of a nationally representative sample of 230,870 women (year 2019-21) was undertaken to explore the trends, distribution, and determinants of CS deliveries in India and within states. Multivariable analyses were performed to determine the proximate variables associated with CS and elective CS. The relative interaction effect of confounding factors, such as number of antenatal care (ANC) visits, place of residence, and wealth status, on cesarean delivery was assessed. A composite index was generated using trust, support, and intimate partner violence variables (termed the partner human capital index [PHI]) to study its influence on CS deliveries, with a low PHI indicating abusive partner and a high PHI indicating supportive partner. Statewise spatial distribution of the most significantly associated factors, namely, wealth quintile and ANC checkups, were also analyzed. RESULTS: The overall prevalence of CS was 21.50% (49,634/230,870) which had risen from 16.72% (2312/13,829) in 1998-99. The adjusted odds of CS deliveries were significantly higher among women who were highly educated (odds ratio [OR] 7.30, 95% CI 7.02-7.60; P<.001), had 4 or more ANC visits (OR 2.28, 95% CI 2.15-2.42; P<.001), belonging to the high-wealth quintile (OR 7.87, 95% CI 7.57-8.18; P<.001), and from urban regions. Increasing educational level of the head of the household (OR 3.05, 95% CI 2.94-3.16; P<.001) was also found to be a significant determinant of CS deliveries. The odds of selection of elective and emergency CS were also significantly higher among women from richer families (OR 1.66, 95% CI 1.25-2.21; P<.001) and those belonging to Christian religion (OR 1.67, 95% CI 1.14-2.43; P=.008). Adjusting the cesarean delivery by PHI, the odds of outcome were significantly higher among women with moderate and high PHI compared with those with low PHI (OR 1.46, 95% CI 1.36-1.56 and OR 1.61, 95% CI 1.49-1.74, respectively; P<.001 for both). The interaction effect result reiterates that women with more than 4 ANC checkups, high PHI, and belonging to the richer wealth quintile were more likely to undergo cesarean delivery (OR 22.22, 95% CI 14.99-32.93; P<.001) compared with those with no ANC visit, low PHI, and poorest women. CONCLUSIONS: The increasing trend of CS deliveries across India is raising concerns. Better education, wealth, and good support from the partner have been incriminated as the contributory factors. There is a need to institute proper monitoring mechanisms to assess the need for CS, especially when performed electively.

Assessment of interleukin 1 receptor antagonist (IL-1RA) levels in children with and without community acquired pneumonia: a hospital based case-control study.

The primary objective was to compare serum interleukin-1 receptor antagonist (IL-1RA) levels in cases of community acquired pneumonia (CAP) and healthy age-gender-matched controls. The secondary objective was to compare serum IL-1RA levels in cases which were positive or negative for Streptococcus pneumoniae in the blood by real-time-polymerase chain reaction (RT-PCR). Hospitalized children with World Health Organization defined CAP, aged 2-59 months, were included as cases. Healthy controls were recruited from the immunization clinic of the hospital. Enzyme-linked immunosorbent assay (ELISA) test was used to detect serum IL-1RA levels. Identification of S.pneumoniae in blood was done by RT-PCR. From October 2019 to October 2021, 330 cases (123, 37.27% female) and 330 controls (151, 45.75% females) were recruited. Mean serum IL-1RA levels (ng/ml) were 1.36 ± 0.95 in cases and 0.25 ± 0.25 in controls (p < 0.001). Within cases, serum IL-1RA levels were significantly higher in those whose RT-PCR was positive for S.pneumoniae. Thus serum IL-1RA levels may be evaluated as a surrogate marker of S.pneumoniae in future studies.

The main purpose of the study was to compare the levels of a protein in the blood that is part of the immune system, called interleukin-1 receptor antagonist (IL-1RA) which binds to the same site in the body as an antibody does when it is fighting certain diseases, like pneumonia. We then compared the levels of this protein, IL-1RA, in hospitalized cases of community acquired pneumonia (CAP), caused from exposure to germs in the community, rather than obtained or contracted in a hospital, to that found in healthy people or 'controls' recruited from an immunization clinic. Cases and controls were matched for age and gender. The secondary objective of our study was to compare the level of IL-1RA protein in the blood in cases that were positive for the bacteria Streptococcus pneumoniae measured in the blood by a molecular test called real-time-polymerase chain reaction which can detect a very small amounts of a protein that is uniquely found in the S.pneumoniae bacteria that causes CAP. This case­control study was conducted in a large teaching institution that receives referrals from the other hospitals in northern India. It was found that serum IL-1RA levels were raised in cases of CAP, especially those which were possibly due to S.pneumoniae.

A Historical Perspective on Chronic Obstructive Pulmonary Disease: From Past to Present.

René-Théophile-Hyacinthe Laennec in his book "Treatise of the Diseases of the Chest" discussed the emphysema in 1821. Chronic obstructive pulmonary disease (COPD) has been around for at least 202 years, from 1821 to 2023 (but the disease itself is much older than that). It is believed that William Briscoe first used the term COPD in June 1965, at the 9th Aspen Emphysema Conference. COPD was first defined by the CIBA guest symposium in 1959 and the American Thoracic Society Committee on Diagnostic Standards in 1962; recent definition of COPD was released by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report 2023. In 1990, it was sixth leading cause of death and in 2020 COPD becomes third leading cause of death. GOLD update 2023 also proposed taxonomy (etiotypes), classification of COPD based on risk factors, and ABE assessment tool for COPD. Now concept of early-COPD, pre-COPD, and, mild-COPD are also emerging, which are helpful in better understanding of COPD. Here, we have discussed historical landmarks, definition, burden, taxonomy, classification, different concept of disease, ABE assessment tool, personalized medicine, and brief description of GOLD and World COPD Day from past to present.

Nanoencapsulation of Docetaxel Induces Concurrent Apoptosis and Necroptosis in Human Oral Cancer Cells (SCC-9) via TNF-α/RIP1/RIP3 Pathway.

Human oral squamous cell carcinoma is the sixth most frequent malignant cancer, with an unacceptably high death rate that affects people's health. Albeit, there are several clinical approaches for diagnosing and treating oral cancer they are still far from ideal. We previously synthesised and characterised the docetaxel nanoformulation (PLGA-Dtx) and discovered that docetaxel nanoencapsulation may suppress oral cancer cells. The goal of this study was to figure out the mechanism involved in the suppression of oral cancer cell proliferation. We discovered that PLGA-Dtx inhibited SCC-9 cell growth considerably as compared to free docetaxel (Dtx), and that the viability of SCC-9 cells treated with PLGA-Dtx was decreased dose-dependently. MTT assay showed that PLGA-Dtx selectively inhibited the growth of PBMCs from oral cancer patients while sparing PBMCs from normal healthy controls. Further, flow cytometry analysis showed that PLGA-Dtx induced apoptosis and necroptosis in SCC-9 cells. G2/M cell cycle arrest has been confirmed on exposure of PLGA-Dtx for 24 h in SCC-9 cells. Interestingly, western blot investigation found that PLGA-Dtx increased the amounts of necroptic proteins and apoptosis-related proteins more efficiently than Dtx. Furthermore, PLGA-Dtx was more effective in terms of ROS generation, and mitochondrial membrane potential depletion. Pretreatment with necroptosis inhibitor Nec-1 efficiently reversed the ROS production and further recover MMP caused by PLGA-Dtx. Overall, this study revealed a mechanistic model of therapeutic response for PLGA-Dtx in SCC-9 cells and proposed its potency by inducing cell death via activation of concurrent apoptosis and necroptosis in SCC-9 cells via TNF-α/RIP1/RIP3 and caspase-dependent pathway.

Increased Serum Levels of Matrix-metalloproteinase-9, Cyclo-oxygenase-2 and Prostaglandin E-2 in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Chronic obstructive pulmonary disease (COPD), a heterogeneous lung disorder that is characterized by airflow obstruction and the third leading cause of death, globally. COPD is influenced by environmental and genetic factors. Here, we measured the serum level of matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE-2) and reveal the correlation between their levels in COPD subjects. In this study, we included a total of 79 COPD and 79 healthy controls. We assessed demographic profile, risk factors, respiratory symptoms, clinical history, COPD Assessment Test (CAT) score and spirometry. Further, we determined the serum levels of MMP-9, COX-2 and PGE-2 by enzyme-linked immunosorbent assay (ELISA). The correlation between their serum levels was also determined. Among the studied population age, gender, body mass index and socioeconomic status were comparable. Serum levels of MMP-9, COX-2 and PGE-2 were significantly increased in the COPD group than in healthy controls (P < 0.0001). Moreover, MMP-9, COX-2 and PGE-2 levels were increased with the GOLD grades and CAT score (> 10). Serum levels of MMP-9, COX-2 and PGE-2 was enhanced in patients with larger clinical history (> 20 years) than those with lower clinical history (< 10 years). Serum levels of MMP-9 and COX-2; MMP-9 and PGE-2; COX-2 and PGE-2 showed a positive correlation (P < 0.0001) with the COPD group. Our data demonstrate that serum levels of MMP-9, COX-2 and PGE-2 were correlated with the GOLD grade, CAT score and clinical history of the COPD group, pointing that they can be used as a indicators to understand the disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-021-00973-2.

Correction: Functional male accessory glands and fertility in Drosophila require novel ecdysone receptor.

[This corrects the article DOI: 10.1371/journal.pgen.1006788.].

Functional male accessory glands and fertility in Drosophila require novel ecdysone receptor.

In many insects, the accessory gland, a secretory tissue of the male reproductive system, is essential for male fertility. Male accessory gland is the major source of proteinaceous secretions, collectively called as seminal proteins (or accessory gland proteins), which upon transfer, manipulate the physiology and behavior of mated females. Insect hormones such as ecdysteroids and juvenoids play a key role in accessory gland development and protein synthesis but little is known about underlying molecular players and their mechanism of action. Therefore, in the present study, we examined the roles of hormone-dependent transcription factors (Nuclear Receptors), in accessory gland development, function and male fertility of a genetically tractable insect model, Drosophila melanogaster. First, we carried out an RNAi screen involving 19 hormone receptors, individually and specifically, in a male reproductive tissue (accessory gland) for their requirement in Drosophila male fertility. Subsequently, by using independent RNAi/ dominant negative forms, we show that Ecdysone Receptor (EcR) is essential for male fertility due to its requirement in the normal development of accessory glands in Drosophila: EcR depleted glands fail to make seminal proteins and have dying cells. Further, our data point to a novel ecdysone receptor that does not include Ultraspiracle but is probably comprised of EcR isoforms in Drosophila male accessory glands. Our data suggest that this novel ecdysone receptor might act downstream of homeodomain transcription factor paired (prd) in the male accessory gland. Overall, the study suggests novel ecdysone receptor as an important player in the hormonal regulation of seminal protein production and insect male fertility.

Correction: Functional male accessory glands and fertility in Drosophila require novel ecdysone receptor.

[This corrects the article DOI: 10.1371/journal.pgen.1006788.].

Functional characterisation of ADP ribosylation factor-like protein 15 in rheumatoid arthritis synovial fibroblasts.

OBJECTIVES: ARL15 is a novel susceptibility gene identified in a recent GWAS in a north Indian rheumatoid arthritis (RA) cohort. However, the role of ARL15 or ARF family genes in RA aetiology remains unknown. Therefore, we aimed to i) establish the expression of ARL15 in rheumatoid arthritis synovial fibroblasts (RASF) and ii) its functional characterisation by assessing its effects on major inflammatory cytokines and interacting partners using a knockdown approach. METHODS: RASF were cultured from synovial tissue obtained from RA patients (n=5) and osteoarthritis (OA) patients (n=3) serving as controls. Expression of ARL15, ARF1 and ARF6 in RASF was checked by semi-quantitative PCR and western blots; and altered expression of ARL15, if any, by induction of RASF with TNF using real-time PCR. The effect of ARL15 on the expression of adiponectin, adiponectin receptor I, IL6 and GAPDH and on cell mobility by invasion and migration assays were assessed by siRNA mediated gene knockdown. RESULTS: Expression of ARL15, ARF1 and ARF6 was confirmed in RASF and OASF samples but ARL15 expression remained unaltered on TNF induction. Notably, ARL15 knockdown resulted in downregulation of IL6 and GAPDH, upregulation of adiponectin and adiponectin receptor I genes; and significant reduction in migration and invasion of RASF. Genemania showed significant interactions of ARL15 with genes responsible for insulin resistance and phospholipase D. CONCLUSIONS: This first report on ARL15 expression in RASF and its likely role in inflammation and metabolic syndromes through a TNF independent pathway, encourages hypothesis-free studies to identify additional pathways underlying RA disease biology.

Economic Burden of Accidents and Injuries in India: What Does 75th Round of National Sample Survey Imply?

Background: Accidents and injuries constitute a sizable share of mortality and morbidity in low- and middle-income countries. This affects the most productive age group and increases disability-adjusted life years (DALYs). It results in a substantial financial burden on the households. To explore the economic burden of accidents and Injuries on Indian households and to find how the catastrophic health expenditure (CHE) from accidents and injuries affects the population. Another objective is to explore Catastrophic out-of-pocket expenditures (OOPE) patterns and distressed financing of households in India. Materials and Methods: The study used data from the 75th round of nationally representative surveys, that is, the National Sample Survey (NSS). Authors have analyzed the data using descriptive binary logistic regression analysis to estimate the rate and average days of hospitalization, average OOPE, and share of the population experiencing the catastrophic impact from the health expenditure separately from the public and private healthcare institutions. Results: The study observed that hospitalization in the private sector imposes 72% of households incur CHE at more than 10% cut-off and 41% at more than 25% cut-off. In comparison, it is less in the public sector, with 22% of households incurring CHE at more than 10% of annual per capita household income and 9% at more than 25%. Conclusion: The increasing incidence of road traffic accidents (RTA) is a concern for the overstretched health system. The government should provide better healthcare facilities and universal health insurance coverage to ensure patients' speedy recovery and financial security.

Clinical outcome post treatment of anemia in pregnancy with intravenous versus oral iron therapy: a systematic review and meta-analysis.

Oral iron therapy is often the most common way of treating anaemia; however intravenous iron is considered effective due to rapid iron replenishment. We have dearth of evidence on clinical outcomes post treatment of anaemia. We have searched studies published in English in PubMed, Cochrane, Scopus, ProQuest, and Google Scholar. Our study analysed the clinical outcomes amongst neonates and mother and the adverse events post treatment and assessed the mean change in maternal haemoglobin concentration in both the groups. Forest plots for the clinical outcomes are presented. From a total of 370 studies, 34 Randomized and quasi experimental studies comparing clinical outcomes post-treatment of anaemia in pregnancy were included for quantitative evidence synthesis. Pooled results of maternal clinical outcomes using random effect model [OR: 0.79 (95% CI 0.66; 0.95); 10 outcomes; 17 studies] showed statistically significant difference among both the groups [Moderate quality evidence]; however no significant difference [OR: 0.99 (95% CI 0.86; 1.14); 7 outcomes; 8 studies] have been observed for neonatal complications [Low quality evidence]. The study found that pregnant women receiving IV iron were significantly less likely to experience adverse events as compared with those receiving oral iron [OR 0.39;  (95% CI 0.26-0.60)]; 34 studies; 13,909 women; [Low quality evidence]. Findings from meta-regression analysis showed that IV iron is more likely to reduce maternal complications by 21% compared to oral iron. Increase in odds of adverse maternal outcomes was observed due to increase in gestational age and publication year but no effect for the type of drug used. IV iron increases Hb more and at a higher pace than oral iron. Intravenous iron is more likely to avert adverse maternal outcomes and adverse reactions. However, there is no conclusive evidence on its effectiveness on individual maternal outcome or neonatal outcome/s. Protocol registered with PROSPERO CRD42022368346).

ARL15 and its Multiple Disease Association: Emerging Functions and Potential Therapeutic Application.

ARL15 is a member of the RAS superfamily of small GTPases and is associated with several metabolic traits, including increased risk of diabetes, rheumatoid arthritis and lipid metabolism disorders. The ARL15 gene encodes for an uncharacterized small GTP binding protein. Its precise role in human physiology remains unknown, but several genetic association studies have recognized different variants in this gene to be statistically associated with numerous traits and complex diseases. Here, we provided the unique features of ARL15 small G protein, its association with varied metabolic and lifestyle diseases, its function in vesicular and lipid trafficking, and its binding partners. We outlined this protein as a promising and emerging therapeutic target to combat metabolic disorders like cardiovascular diseases, diabetes and rheumatoid arthritis. The review provides a comprehensive description of the current advancements in ARL15 research with a perspective that focused research will position this small GTPase as a viable target for the treatment of rheumatoid arthritis.

Contributing factors for reduction in maternal mortality ratio in India.

Maternal mortality ratio (MMR) estimates have been studied over time for understanding its variation across the country. However, it is never sufficient without accounting for presence of variability across in terms of space, time, maternal and system level factors. The study endeavours to estimate and quantify the effect of exposures encompassing all maternal health indicators and system level indicators along with space-time effects influencing MMR in India. Using the most recent level of possible -factors of MMR, maternal health indicators from the National Family Health Survey (NFHS: 2019-21) and system level indicators from government reports a heatmap compared the relative performance of all 19 SRS states. Facet plots with a regression line was utilised for studying patterns of MMR for different states in one frame. Using Bayesian Spatio-temporal random effects, evidence for different MMR patterns and quantification of spatial risks among individual states was produced using estimates of MMR from SRS reports (2014-2020). India has witnessed a decline in MMR, and for the majority of the states, this drop is linear. Few states exhibit cyclical trend such as increasing trends for Haryana and West Bengal which was evident from the two analytical models i.e., facet plots and Bayesian spatio- temporal model. Period of major transition in MMR levels which was common to all states is identified as 2009-2013. Bihar and Assam have estimated posterior probabilities for spatial risk that are relatively greater than other SRS states and are classified as hot spots. More than the individual level factors, health system factors account for a greater reduction in MMR. For more robust findings district level reliable estimates are required. As evident from our study the two most strong health system influencers for reducing MMR in India are Institutional delivery and Skilled birth attendance.

The severity of non-smoking chronic obstructive pulmonary disease is correlated with biomass fuel exposure and COPD assessment test score.

BACKGROUND AND OBJECTIVE: Tobacco smoking is an established risk factor for chronic obstructive pulmonary disease (COPD). Current evidence suggests that non-tobacco-related risk factors vary geographically and are less understood than smoking. This study aims to compare the risk factors, symptoms, and clinical features of smoking (S-COPD) and non-smoking (NS-COPD) in a COPD population. MATERIALS AND METHODS: In this retrospective cross-sectional study, 489 COPD patients were screened. Data on socio-demographics, smoking and medical history, other risk factors, symptoms, and clinical characteristics including COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) Dyspnea Scale were examined. RESULTS: Of the total selected 416 COPD patients, 35.34% were NS-COPD while 64.66% were S-COPD. S-COPD was predominant in males, whereas NS-COPD was predominant in females (P < 0.0001). In NS-COPD, biomass fuel exposure was a major risk factor (P < 0.0001), and 61% of subjects had a biomass fuel exposure index of >60. In bivariate and multivariate analyses, no risk factors were correlated with forced expiratory volume in 1 second (FEV1)% predicted, while among clinical features, duration of illness (P = 0.001) was correlated with lower values of FEV1 in the multivariate table of S-COPD. In the multivariate analysis, biomass fuel exposure (P = 0.039) and CAT score (P < 0.0001) were correlated with FEV1(%) in NS-COPD. CONCLUSION: Biomass fuel exposure is a substantial risk factor for NS-COPD and was correlated with FEV1(%) predicted. In addition, the CAT score correlated with disease severity in patients with NS-COPD. The development of COPD in non-smokers is being recognized as a separate phenotype and it should be managed according to risk factors.

Hidden hunger in patients with type 2 diabetes (T2D) and its effect on glycaemic control: a protocol for systematic review and meta-analysis.

INTRODUCTION: Hidden hunger or micronutrient deficiencies are quite common in many parts of the world, particularly in the countries of sub-Saharan Africa and South Asia. Micronutrient deficiencies may impact insulin signalling pathways and glucose metabolism, potentially accelerating the onset and development of type 2 diabetes (T2D). This review aims to estimate the prevalence of multiple micronutrient deficiencies among patients with T2D and assess the effect of their deficiency on glycaemic control. METHODOLOGY: The review follows the Cochrane Handbook and PRISMA 2020 guidelines. It includes all eligible studies reporting the prevalence of micronutrient deficiencies and their effect on glycaemic control in T2D patients. We would undertake a comprehensive literature search across databases: PubMed, Scopus, EMBASE, LILACS, ProQuest, Google Scholar and grey literature, and identify the studies meeting the inclusion criteria. We would perform data extraction using a prepiloted data extraction sheet and record relevant study characteristics and outcomes. ANALYSIS: Data will be analysed using JBI Sumari software and R software. Pooled prevalence/incidence of micronutrient deficiency will be estimated, and variance will be stabilised using logit transformation and a double-arcsine transformation of the data. The OR and risk ratio of glycaemic control among T2D cases with and without micronutrient deficiency will be estimated using the 'rma' function under the 'meta' and 'metafor' packages.The study findings will have implications for diabetes management strategies and may inform interventions targeting improved glycaemic control through addressing micronutrient deficiencies. ETHICS AND DISSEMINATION: This systematic review will be based on the scientific information available in the public domain; therefore, ethics approval is not required. We will share the study findings at national and international conferences and submit them for publication in relevant scientific journals. PROSPERO REGISTRATION NUMBER: CRD42023439780.