Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries.

Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies. Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival. Design, Setting, and Participants: This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023. Main Outcomes and Measures: Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies). Results: Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable. Conclusions and Relevance: In this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.

HPV-YAP1 oncogenic alliance drives malignant transformation of fallopian tube epithelial cells.

High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the malignant transformation of FTECs. HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC.

Toxicity assessment of heavy metals translocation in maize grown in the Ganges delta floodplain soils around the Payra power plant in Bangladesh.

As a cereal crop, maize ranked third place after wheat and rice in terms of land area coverage for its cultivation, and in Bangladesh, it ranked second place after rice in its production. As the substitution of wheat products, maize has been used widely in baking for human consumption and animal fodder. However, maize grown in this soil around the coal-burning power plant may cause heavy metals uptake that poses a risk to humans. The study was conducted at the maize fields in the Ganges delta floodplain soils of Bangladesh to know the concentration of eight heavy metals (Ni, Cr, Cd, Mn, As, Cu, Zn, and Pb) in soil and maize samples using an inductively coupled plasma mass spectrometer (ICP-MS) and to estimate the risk of heavy metals in maize grains. Mean concentrations of heavy metals (mg/kg) in soil were in decreasing order of Zn (10.12) > Cu (10.02) > Mn (5.48) > Ni (4.95) > Cr (3.72) > As (0.51) > Pb (0.27) > Cd (0.23). The plant tissues showed the descending order of heavy metal concentration as roots > grains > stems > leaves. BCF values for As, Cd, Pb, and Mn in roots were higher than 1.0, indicating considerable accumulation of these elements in maize via roots. Total hazard quotient (Æ©THQ) of heavy metals through maize grain consumption was 3.7E+00 and 3.9E+00 for adults and children, respectively, indicating non-cancer risk to the consumers. Anthropogenic influences contributed to the heavy metals enrichment in the Ganges delta floodplain soils around the thermal plant, and potential risks (non-carcinogenic and carcinogenic) were observed due to the consumption of maize grain cultivated in the study area.

Understanding cervical cancer awareness in hard-to-reach areas of Bangladesh: A cross-sectional study involving women and household decisionmakers.

INTRODUCTION: In Bangladesh, the uptake of cervical cancer screening is low. Lack of knowledge and understanding of symptoms and risk factors contributes to low screening uptake. The purpose of this study was to explore the knowledge of cervical cancer risk factors and symptoms and to measure the association with socio-demographic characteristics among women and household decisionmakers living in hard-to-reach areas of Bangladesh. METHODS: A cross-sectional survey was conducted in five districts in Bangladesh among women aged between 30 and 60 years, their husbands, and their mothers-in-law from April to September 2022. Data were collected using a modified version of the validated AWACAN questionnaire tool. The significance level was considered at p-value <0.05 and odds ratios with 95% confidence. RESULTS: Nearly 50% of participating women in hard-to-reach areas of Bangladesh and their family decisionmakers had low levels of knowledge of the risk factors and symptoms of cervical cancer. Only 20% of respondents in our survey knew about HPV, the most important risk factor for developing cervical cancer. Most respondents were familiar with the terminology of cervical cancer as a disease; however, approximately 40% of respondents did not know that not adhering to cervical cancer screening could be seen as a risk factor. Women do not make decisions about participation in cervical cancer screening on their own. Knowledge of cervical cancer risk factors and symptoms among decisionmakers was significantly associated with higher education and higher household monthly expenditure. CONCLUSION: Women, their husbands, and mothers-in-law in hard-to-reach areas of Bangladesh had limited knowledge about cervical cancer risk factors and symptoms. Engaging these key decision-makers in targeted health education is vital to improve screening uptake. Conduction of future research to identify and address screening barriers is also essential for effective prevention efforts.

Roles of Hydrogen Sulfide (H2S) as a Potential Therapeutic Agent in Cardiovascular Diseases: A Narrative Review.

Cardiovascular disease (CVD) stands as one of the leading causes of morbidity and mortality worldwide, and the continued search for novel therapeutics is vital for addressing this global health challenge. Over the past decade, hydrogen sulfide (H2S) has garnered significant attention in the field of medical research, as it has been proven to be a cardioprotective gaseous signaling molecule. It joins nitric oxide and carbon monoxide as endogenously produced gasotransmitters. As for its mechanism, H2S functions through the posttranslational addition of a sulfur group to cysteine residues on target proteins in a process called sulfhydration. As a result, the observed physiological effects of H2S can include vasodilation, anti-apoptosis, anti-inflammation, antioxidant effects, and regulation of ion channels. Various studies have observed the cardioprotective benefits of H2S in diseases such as myocardial infarction, ischemia-reperfusion injury, cardiac remodeling, heart failure, arrhythmia, and atherosclerosis. In this review, we discuss the mechanisms and therapeutic potential of H2S in various CVDs.

Diabetic Neuropathy: A Guide to Pain Management.

PURPOSE OF REVIEW: Diabetic neuropathy is a common complication of diabetes mellitus (DM) and can affect up to 50% of DM patients during their lifetime. Patients typically present with numbness, tingling, pain, and loss of sensation in the extremities. Since there is no treatment targeting the underlying mechanism of neuropathy, strategies focus on preventative care and pain management. RECENT FINDINGS: Up to 69% of patients with diabetic neuropathy receive pharmacological treatment for neuropathic pain. The United States Food and Drug Administration (FDA) confirmed four drugs for painful diabetic neuropathy (PDN): pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch. Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) both show promise in reducing pain in DM patients. Despite the high burden associated with PDN, effective management remains challenging. This update covers the background and management of diabetic neuropathy, including its epidemiology, pathogenesis, preventative care, and current therapeutic strategies.

Rare case of human Ancylostoma ceylanicum infection in Bangladesh.

The zoonotic hookworm species Ancylostoma ceylanicum has drawn more attention recently because of its potential impact on public health. Although A. duodenale and Necator americanus are more common, A. ceylanicum is still known to play a major role in human infections, particularly in regions where close human-animal interactions are prevalent. While there has been a notable increase in documenting the presence of A. ceylanicum in the Asia-Pacific area, bottlenecks remains in understanding its epidemiology in Bangladesh. This report highlights the first documented case of Ancylostoma ceylanicum infection isolated and identified in a 15-year-old girl experiencing frequent diarrhea and weakness, residing in an urban tea garden area in Sylhet, Bangladesh. Microscopic examination of stool samples revealed the presence of hookworm eggs and subsequent culture led to the observation of larvae. Molecular investigation by amplifying Internal Transcribed Spacer (ITS1+) regions of the ribosomal deoxyribonucleic acid (rDNA) confirmed the infection as A. ceylanicum. The identification of Ancylostoma ceylanicum in a human host in Bangladesh carries significant implications for global health. The careful measurement of eggs and larvae, coupled with molecular analysis, serves as an appropriate diagnostic strategy for confirming the infections. This finding emphasizes the emergence of A. ceylanicum as a zoonotic infection in endemic regions and calls for increased awareness among healthcare professionals and the general public.

Unveiling the molecular basis of paracetamol-induced hepatotoxicity: Interaction of N-acetyl-p-benzoquinone imine with mitochondrial succinate dehydrogenase.

Background and aim: N-acetyl-p-benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard. Method: Molecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant. Result: The molecular binding affinity score for APAP and NAPQI with SDH was predicted -6.5 and -6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH. Conclusion: This study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.

Uncovering Novel Protein Partners of Inducible Nitric Oxide Synthase in Human Testis.

Peroxidative damage to human spermatozoa has been shown to be the primary cause of male infertility. The possible role of nitric oxide (NO) in affecting sperm motility, capacitation, and acrosome reaction has been reported, too. The overproduction of NO by the enzyme inducible nitric oxide synthase (iNOS) could be responsible as it has been implicated in the pathogenesis of many diseases. There have been many studies on regulating iNOS function in various tissues, especially by protein-protein interaction; however, no study has looked for iNOS-interacting proteins in the human testis. Here, we have reported the identification of two proteins that interact with iNOS. We initially undertook a popular yeast two-hybrid assay to screen a human testis cDNA library in yeast using an iNOS-peptide fragment (amino acids 181-335) as bait. We verified our data using the mammalian chemiluminescent co-IP method; first, employing the same peptide and, then, a full-length protein co-expressed in HEK293 cells in addition to the candidate protein. In both cases, these two protein partners of iNOS were revealed: (a) sperm acrosome-associated 7 protein and (b) retinoblastoma tumor-suppressor binding protein.

Evaluation of a disability-inclusive ultra-poor graduation programme in Uganda: study protocol for a cluster-randomised controlled trial with process evaluation.

BACKGROUND: There is little evidence on how to support ultra-poor people with disabilities to adopt sustainable livelihoods. The Disability-Inclusive Graduation (DIG) programme targets ultra-poor people with disabilities and/or women living in rural Uganda. The programme is an adaptation of an ultra-poor graduation model that has been shown to be effective in many contexts but not evaluated for people with disabilities. METHODS: The DIG programme works with project participants over a period of 18 months. Participants receive unconditional cash transfers for 6 months, training, access to savings-and-loans groups, and a capital asset that forms the basis of their new livelihood. The programme is also adapted to address specific barriers that people with disabilities face. Eligible households are clustered by geographical proximity in order to deliver the intervention. Eligibility is based on household screening to identify the 'ultra-poor' based on proxy means testing-both households with and without people with disabilities are included in the programme. Clusters are randomly selected prior to implementation, resulting in 96 intervention and 89 control clusters. The primary outcome of the trial is per-capita household consumption. Before the start of the intervention, a baseline household survey is conducted (November 2020) among project participants and those not offered the programme, a similar endline survey is conducted with participants with disabilities at the end of programme implementation in July 2022, and a second endline survey for all participants in October 2023. These activities are complemented by a process evaluation to understand DIG programme implementation, mechanisms, and context using complementary qualitative and quantitative methods. Ethical approval for the research has been received from Mildmay Uganda Research Ethics Committee and London School of Hygiene and Tropical Medicine. DISCUSSION: DIG is a promising intervention to evaluate for people with disabilities, adapted to be disability inclusive across programme components through extensive consultations and collaboration, and has proven efficacy at reducing poverty in other marginalised groups. However, evaluating a well-evidenced intervention among a new target group poses ethical considerations. TRIAL REGISTRATION: Registry for International Development Impact Evaluations, RIDIE-STUDY-ID-626008898983a (20/04/22). ISRCTN registry, ISRCTN78592382 . Retrospectively registered on 17/08/2023.

Identifying delays in healthcare seeking and provision: The Three Delays-in-Healthcare and mortality among infants and children aged 1-59 months.

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted.

Post-mortem investigation of deaths due to pneumonia in children aged 1-59 months in sub-Saharan Africa and South Asia from 2016 to 2022: an observational study.

BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network. METHODS: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards. FINDINGS: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus. INTERPRETATION: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens. FUNDING: Bill & Melinda Gates Foundation.

An integrated coastal ecosystem monitoring strategy: Pilot case in Naf-Saint Martin Peninsula, Bangladesh.

Rapid population growth creating an excessive pressure on the marine environment and thus monitoring of marine ecosystem is essential. However, due to high technical and financial involvement, monitoring of coastal ecosystem is always challenging in developing countries. This study aims to develop an integrated coastal ecosystem monitoring system that combines scientific sampling, numerical model simulation and citizen science observations to monitor the coastal ecosystem of Bangladesh. This concept of integrated monitoring approach was piloted from January 2022 to April 2023 at the South East coastal zone of Bangladesh. Scientific sampling and numerical model simulations were performed for temperature and salinity data collection. Citizen science approach was employed to collect data on environmental conditions, fisheries, plankton, other marine resources, and plastic pollution. Numerical model simulations and citizen scientists observations of temperature and salinity showed good agreement with the scientifically collected data. In addition, citizen scientists observations on fisheries, plankton, other marine resources and plastic pollution were also in line with the existing database and previous studies. The proposed integrated monitoring approach presents a viable technique, creating a new avenue for coastal and marine ecosystem monitoring where infrastructural facilities are limited.

Morpho-molecular investigation of ectoparasitic infestation of companion animals in Sylhet city, Bangladesh.

Ticks (Ixodida) and Fleas (Siphonaptera) are considered among the most important arthropod of public health concern due to their ability to transmit vector-borne pathogens to humans. By sharing a common environment, vector-borne diseases constituted major setbacks to the development of a pet population in Bangladesh. This study aimed to determine companion animal-associated ticks and fleas based on morpho-molecular approaches. Between December 2021 and May 2022, 74 animals (62 cats and 12 dogs) were examined, of which 17 (27.4%) cats and 9 (75.0%) dogs had ectoparasitic infestations, with 35.1% overall prevalence. Morphometrical examination showed the ectoparasites in these animals were Ctenocephalides spp. (flea) and Riphicephalus spp. (tick). Genetic analysis using the mitochondrial markers i.e. Cytochrome c oxidase subunit 1 (cox1) revealed the presence of two flea species i.e., Ctenocephalides canis, Ctenocephalides felis, and one tick species Rhipicephalus sanguineus. Interviews of animal owners indicate that 35.14% of them had no concern about ectoparasitic infestation or ectoparasites-borne diseases. Our results indicated that fleas and ticks were the most common ectoparasites in companion animals of this area. The zoonotic nature of some ectoparasites can be regarded as a public health alert. The findings will assist epidemiologists and policymakers in offering customized guidance for upcoming monitoring and preventive tactics in this area.

Warming influences carbon and nitrogen assimilation between a widespread Ericaceous shrub and root-associated fungi.

High-latitude ecosystems are warming faster than other biomes and are often dominated by a ground layer of Ericaceous shrubs, which can respond positively to warming. The carbon-for-nitrogen (C-for-N) exchange between Ericaceous shrubs and root-associated fungi may underlie shrub responses to warming, but has been understudied. In a glasshouse setting, we examined the effects of warming on the C-for-N exchange between the Ericaceous shrub Empetrum nigrum ssp. hermaphroditum and its root-associated fungi. We applied different 13 C and 15 N isotope labels, including a simple organic N form (glycine) and a complex organic N form (moss litter) and quantified their assimilation into soil, plant biomass, and root fungal biomass pools. We found that warming lowered the amount of 13 C partitioned to root-associated fungi per unit of glycine 15 N assimilated by E. nigrum, but only in the short term. By contrast, warming increased the amount of 13 C partitioned to root-associated fungi per unit of moss 15 N assimilated by E. nigrum. Our study suggests that climate warming affects the short-term exchange of C and N between a widespread Ericaceous shrub and root-associated fungi. Furthermore, while most isotope tracing studies use labile N sources, we demonstrate that a ubiquitous recalcitrant N source may produce contrasting results.

Model organism life extending therapeutics modulate diverse nodes in the drug-gene-microbe tripartite human longevity interactome.

Advances in antiaging drug/lead discovery in animal models constitute a large body of literature on novel senotherapeutics and geroprotectives. However, with little direct evidence or mechanism of action in humans-these drugs are utilized as nutraceuticals or repurposed supplements without proper testing directions, appropriate biomarkers, or consistent in-vivo models. In this study, we take previously identified drug candidates that have significant evidence of prolonging lifespan and promoting healthy aging in model organisms, and simulate them in human metabolic interactome networks. Screening for drug-likeness, toxicity, and KEGG network correlation scores, we generated a library of 285 safe and bioavailable compounds. We interrogated this library to present computational modeling-derived estimations of a tripartite interaction map of animal geroprotective compounds in the human molecular interactome extracted from longevity, senescence, and dietary restriction-associated genes. Our findings reflect previous studies in aging-associated metabolic disorders, and predict 25 best-connected drug interactors including Resveratrol, EGCG, Metformin, Trichostatin A, Caffeic Acid and Quercetin as direct modulators of lifespan and healthspan-associated pathways. We further clustered these compounds and the functionally enriched subnetworks therewith to identify longevity-exclusive, senescence-exclusive, pseudo-omniregulators and omniregulators within the set of interactome hub genes. Additionally, serum markers for drug-interactions, and interactions with potentially geroprotective gut microbial species distinguish the current study and present a holistic depiction of optimum gut microbial alteration by candidate drugs. These findings provide a systems level model of animal life-extending therapeutics in human systems, and act as precursors for expediting the ongoing global effort to find effective antiaging pharmacological interventions.Communicated by Ramaswamy H. Sarma.

Correction: Prevalence of anemia in diabetes mellitus in South Asia: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0285336.].

Factors contributing to antibiotic use among children younger than five years old with fever, acute respiratory illness, and diarrhea in Bangladesh.

INTRODUCTION: Increasing antibiotic usage is a leading health threat that develops antibiotic resistance. The current practice of antibiotic use among under-five children are unavailable in Bangladesh. We aim to identify the factors of antibiotic use among under-five children with infectious diseases. METHODOLOGY: A cross-sectional multiple indicators cluster survey (MICS) was conducted in 2019 across Bangladesh. This survey of 23,099 children under the age of five was randomly selected by using a two-stage stratified sampling method. The first stage involved randomly selecting 32,200 enumeration clusters. In second stage, households where 15-45-years-old women lived were randomly selected from within each cluster. The Poisson regression models were performed to estimate the prevalence ratio (PR). RESULTS: We found 36.7% (8447/23,099) under-five children with infectious diseases. The proportion of antibiotic use was reported as 32.6%. Antibiotic use was associated with wealth (poorest vs. rich adjusted prevalence ratio (APR) = 1.07; 95% CI: 0.94-1.22) and mother's education (pre-primary vs. higher: APR = 1.14; 95% CI: 1.03-1.27). Oral and injectable antibiotics were used in cases of fever (30.5%), diarrhea (4.5%), fever with cough (47.6%). Cotrimoxazole (31.0%) and amoxicillin (29.0%) were consumed for fever with cough while cotrimoxazole (14.0%) and amoxicillin (11.0%) were consumed for fever with diarrhea. They received antibiotics from drug stores (71.9%) without prescription and private healthcare (52.1%). CONCLUSIONS: Overall, one-third of the under-five children in Bangladesh consumed antibiotics to treat infectious diseases. Multiple factors contribute to the prevalence of antibiotic use. The results highlight the need to regulate antibiotic use and prioritize national intervention programs.

Secondhand smoke exposure and associated factors among city residents living in multiunit housing in Bangladesh.

BACKGROUND: Secondhand smoke (SHS) poses a high health risk to those living in multiunit housing (MUH) since it can easily spread from unit to unit and throughout the building's communal areas. MUH residents in Bangladesh are particularly vulnerable to SHS due to the absence of smoking restrictions within a housing complex. Therefore, this study aimed to assess the prevalence of SHS exposure and its associated factors among MUH residents living in seven divisional cities of Bangladesh- Dhaka, Chattogram, Rajshahi, Khulna, Sylhet, Barishal, and Rangpur. METHODS: From April 2019 to November 2019, a cross-sectional survey was conducted with 616 MUH residents aged 18 or older who had been residing in MUH for at least two years in the seven divisional cities of Bangladesh. A multivariable logistic regression model was performed to determine the associated factors of SHS exposure. RESULTS: In MUH complexes, more than half (54.9%) of the 616 respondents were exposed to SHS. The key factors positively associated with SHS exposure were females (aOR: 1.8, 95% CI:1.236-2.681), residents with a low monthly family income (aOR: 1.9, 95% CI: 1.162-3.220), those whose family members smoked (aOR: 2.4, 95% CI: 1.537-3.746), and Dhaka city residents (aOR: 1.9, 95% CI: 1.013-3.440). CONCLUSIONS: This study revealed a high prevalence of SHS exposure among Bangladeshi MUH residents. Therefore, a smoking ban is needed in and around MUH complexes to protect non-smoking residents from SHS exposure.

Cardiomyocyte-Targeting Peptide to Deliver Amiodarone.

BACKGROUND: Amiodarone is underutilized due to significant off-target toxicities. We hypothesized that targeted delivery to the heart would lead to the lowering of the dose by utilizing a cardiomyocyte-targeting peptide (CTP), a cell-penetrating peptide identified by our prior phage display work. METHODS: CTP was synthesized thiolated at the N-terminus, conjugated to amiodarone via Schiff base chemistry, HPLC purified, and confirmed with MALDI/TOF. The stability of the conjugate was assessed using serial HPLCs. Guinea pigs (GP) were injected intraperitoneally daily with vehicle (7 days), amiodarone (7 days; 80 mg/kg), CTP-amiodarone (5 days; 26.3 mg/kg), or CTP (5 days; 17.8 mg/kg), after which the GPs were euthanized, and the hearts were excised and perfused on a Langendorff apparatus with Tyrode's solution and blebbistatin (5 µM) to minimize the contractions. Voltage (RH237) and Ca2+-indicator dye (Rhod-2/AM) were injected, and fluorescence from the epicardium split and was captured by two cameras at 570-595 nm for the cytosolic Ca2+ and 610-750 nm wavelengths for the voltage. Subsequently, the hearts were paced at 250 ms with programmed stimulation to measure the changes in the conduction velocities (CV), action potential duration (APD), and Ca2+ transient durations at 90% recovery (CaTD90). mRNA was extracted from all hearts, and RNA sequencing was performed with results compared to the control hearts. RESULTS: The CTP-amiodarone remained stable for up to 21 days at 37 °C. At ~1/15th of the dose of amiodarone, the CTP-amiodarone decreased the CV in hearts significantly compared to the control GPs (0.92 ± 0.05 vs. 1.00 ± 0.03 ms, p = 0.0007), equivalent to amiodarone alone (0.87 ± 0.08 ms, p = 0.0003). Amiodarone increased the APD (192 ± 5 ms vs. 175 ± 8 ms for vehicle, p = 0.0025), while CTP-amiodarone decreased it significantly (157 ± 16 ms, p = 0.0136), similar to CTP alone (155 ± 13 ms, p = 0.0039). Both amiodarone and CTP-amiodarone significantly decreased the calcium transients compared to the controls. CTP-amiodarone and CTP decreased the CaTD90 to an extent greater than amiodarone alone (p < 0.001). RNA-seq showed that CTP alone increased the expression of DHPR and SERCA2a, while it decreased the expression of the proinflammatory genes, NF-kappa B, TNF-α, IL-1ß, and IL-6. CONCLUSIONS: Our data suggest that CTP can deliver amiodarone to cardiomyocytes at ~1/15th the total molar dose of the amiodarone needed to produce a comparable slowing of CVs. The ability of CTP to decrease the AP durations and CaTD90 may be related to its increase in the expression of Ca-handling genes, which merits further study.