Lifestyle practices and associated factors among adults with hypertension: Conquering Hypertension in Vietnam-solutions at the grassroots level study.

BACKGROUND: Vietnam is experiencing an increasing prevalence of hypertension in its adult population. In addition to medical therapy, modifying adverse lifestyle practices is important for effective blood pressure control. There are limited data on unhealthy lifestyle practices in patients with chronic diseases, however, particularly among hypertensive patients living in rural Vietnam. Our study objectives were to examine the prevalence of unhealthy lifestyle practices and associated factors among rural Vietnamese adults with uncontrolled hypertension. METHODS: Data from the baseline survey of a cluster randomized trial among hypertensive Vietnamese adults (2017-2022) were utilized. Information on unhealthy lifestyle practices including smoking, excessive alcohol consumption, physical inactivity, and inadequate fruit and vegetable intake was collected from study participants. The primary study outcome was having ≥2 unhealthy lifestyle practices. A multivariable logistic regression model was used to examine factors associated with the primary study outcome. RESULTS: The mean age of the 671 patients was 67 years and 45.0% were men. Nearly three out of every four participants had one or fewer unhealthy practices, 24.0% had two, and 3.3% had three or all four unhealthy lifestyle practices. Men, individuals who did unpaid work or were unemployed, and individuals with hypertension level III were more likely to have ≥2 unhealthy lifestyle practices, whereas individuals with higher education were less likely to have ≥2 unhealthy lifestyle practices compared with respective comparison groups. CONCLUSIONS: We observed a high prevalence of unhealthy lifestyle practices among rural Vietnamese patients with uncontrolled hypertension. Several demographic factors were associated with a greater number of unhealthy lifestyle practices. Newer interventions and educational programs encouraging lifestyle modification practices are needed to control hypertension among adults living in rural settings of Vietnam.

Deworming and micronutrient status by community open defecation prevalence: An observational study using nationally representative data from India, 2016-2018.

BACKGROUND: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. METHODS AND FINDINGS: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. CONCLUSIONS: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study.

Feasibility of Using an Artificial Intelligence-based Telephone Application for Dietary Assessment and Nudging to Improve the Quality of Food Choices of Female Adolescents in Vietnam: Evidence from a Randomized Pilot Study.

Background: Adolescent nutrition has faced a policy neglect, partly owing to the gaps in dietary intake data for this age group. The Food Recognition Assistance and Nudging Insights (FRANI) is a smartphone application validated for dietary assessment and to influence users toward healthy food choices. Objectives: This study aimed to assess the feasibility (adherence, acceptability, and usability) of FRANI and its effects on food choices and diet quality in female adolescents in Vietnam. Methods: Adolescents (N = 36) were randomly selected from a public school and allocated into 2 groups. The control group received smartphones with a version of FRANI limited to dietary assessment, whereas the intervention received smartphones with gamified FRANI. After the first 4 wk, both groups used gamified FRANI for further 2 wk. The primary outcome was the feasibility of using FRANI as measured by adherence (the proportion of completed food records), acceptability and usability (the proportion of participants who considered FRANI acceptable and usable according to answers of a Likert questionnaire). Secondary outcomes included the percentage of meals recorded, the Minimum Dietary Diversity for Women (MDDW) and the Eat-Lancet Diet Score (ELDS). Dietary diversity is important for dietary quality, and sustainable healthy diets are important to reduce carbon emissions. Poisson regression models were used to estimate the effect of gamified FRANI on the MDDW and ELDS. Results: Adherence to the application was 82% and the percentage of meals recorded was 97%. Acceptability and usability were 97%. MDDW in the intervention group was 1.07 points (95% CI: 0.98, 1.18; P = 0.13) greater than that in the control (constant = 4.68); however, the difference was not statistically significant. Moreover, ELDS in the intervention was 1.09 (95% CI: 1.01, 1.18; P = 0.03) points greater than in the control (constant = 3.67). Conclusions: FRANI was feasible and may be effective to influence users toward healthy food choices. Research is needed for FRANI in different contexts and at scale.The trial was registered at the International Standard Randomized Controlled Trial Number as ISRCTN 10681553.

Utilizing surface plasmon resonance as a novel method for monitoring in-vitro P-glycoprotein efflux.

P-glycoprotein (Pgp) is known for its dichotomous roles as both a safeguarding efflux transporter against xenobiotics and as a catalyst for multidrug resistance. Given the susceptibility of numerous therapeutic compounds to Pgp-mediated resistance, compliance with Food and Drug Administration (FDA) guidelines mandates an in-depth in vitro transport assay during drug development. This study introduces an innovative transport assay that aligns with these regulatory imperatives but also addresses limitations in the currently established techniques. Using Pgp-reconstituted liposomes and employing surface plasmon resonance (SPR), this study developed a distinct method of measuring the relative transport rates of Pgp substrates in a controlled microenvironment. The Pgp substrates selected for this study-quinidine, methadone, and desipramine-resulted in transport ratios that corroborate with trends previously observed. To assess the kinetics of Pgp-mediated transport, the results were analyzed by fitting the data to both currently proposed Pgp substrate translocation models-the vacuum cleaner and flippase models. While the resulting kinetic analysis in this study lends support predominantly to the vacuum cleaner model, this study most notably developed a novel method of assessing Pgp-mediated transport rates and real-time kinetics using surface plasmon resonance.

"Multiplexed screen identifies a Pseudomonas aeruginosa -specific small molecule targeting the outer membrane protein OprH and its interaction with LPS".

The surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly against Pseudomonas aeruginosa , a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) of P. aeruginosa combined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging. We adapted PROSPECT 1 , a target-based, whole-cell screening strategy, to discover small molecule probes that kill P. aeruginosa mutants depleted for essential proteins localized at the OM. We identified BRD1401, a small molecule that has specific activity against a P. aeruginosa mutant depleted for the essential lipoprotein, OprL. Genetic and chemical biological studies identified that BRD1401 acts by targeting the OM ß-barrel protein OprH to disrupt its interaction with LPS and increase membrane fluidity. Studies with BRD1401 also revealed an interaction between OprL and OprH, directly linking the OM with peptidoglycan. Thus, a whole-cell, multiplexed screen can identify species-specific chemical probes to reveal novel pathogen biology.

Utilization of Integrated Child Development Services (ICDS) and its linkages with undernutrition in India.

The Integrated Child Development Services (ICDS) programme has been the central focus of the POSHAN Abhiyaan to combat maternal and child malnutrition under the national nutrition mission in India. This paper examined the linkages between utilization of ICDS and underweight among children aged 6-59 months. The study utilized data from two recent rounds of the National Family Health Survey (NFHS-4 [2015-2016] and NFHS-5 [2019-2021]). Descriptive analyses were used to assess the change in utilization of ICDS and the prevalence of underweight at the national and state levels. Multivariable logistic regressions were performed to examine factors associated with the utilization of ICDS and underweight. Linkages between utilization of ICDS and underweight were examined using the difference-in-differences (DID) approach. Utilization of ICDS increased from 58% in 2015-2016 to 71% in 2019-2021. The prevalence of underweight decreased from 37% to 32% in the same period. Changes in ICDS utilization and underweight prevalence varied considerably across states, socioeconomic and demographic characteristics. Results from decomposition of DID models suggest that improvements in ICDS explained 9%-12% of the observed reduction in underweight children between 2016 and 2021, suggesting that ICDS made a modest but meaningful contribution in addressing undernutrition among children aged 6-59 months in this period.

The relationships between optimal infant feeding practices and child development and attained height at age 2 years and 6-7 years.

Limited evidence exists on the long-term effects of early feeding practices on child growth and development. We examined the relationships between infant feeding practices and child height and development at ages 2 and 6-7 years. We studied 885 mother-child dyads from a randomized controlled trial of preconception supplementation in Vietnam. Early initiation of breastfeeding (EIBF), exclusive breastfeeding (EBF), breastfeeding (BF) duration and minimum dietary diversity (MDD) were assessed using World Health Organization (WHO) guidelines. Child development was assessed by the Bayley Scales of Infant Development-III at 2 years and the Wechsler Intelligence Scale for Children® - IV at 6-7 years. Child height-for-age z-score (HAZ) was calculated from child height and age. Multivariable regression and structural equation models were used in analyses that controlled for confounding. EIBF and EBF at 6 months occurred in 52% and 62% of children, respectively. Mean breastfeeding duration was 18 months and 83% achieved MDD at 1 year. EIBF was associated with motor (ß = 0.13, 95% confidence interval [CI]: 0.00, 0.28) and cognitive development at 2 years (ß = 0.12, 95% CI: -0.01, 0.26), which in turn were positively associated with cognitive development at 6-7 years. EBF was directly associated with development at 6-7 years (ß = 0.21, 95% CI:0.08, 0.34) whereas motor and cognitive development at 2 years explained 41%-75% of the relationship between EIBF and development at 6-7 years. HAZ at 2 years also mediated 70% of the association between MDD at 1 year and HAZ at 6-7 years. BF duration was not associated with child development and HAZ. Early infant feeding practices, especially EIBF and EBF, have important long-term implications for optimizing child linear growth and cognition as they begin school.

Preconception Micronutrient Supplementation Affects Maternal BMI and Body Composition Postpartum: A Randomized Controlled Trial in Vietnam.

BACKGROUND: Although there is growing evidence on the role of preconception nutrition for birth outcomes, limited evidence exists for its effects on maternal health. OBJECTIVES: This study evaluates the impact of preconception micronutrient supplementation on maternal BMI (kg/m2) and body composition at 6 to 7 y postpartum (PP). METHODS: We followed females who participated in a randomized controlled trial of preconception supplementation in Vietnam and delivered live offspring (n = 1599). Females received weekly supplements containing either 2800 µg folic acid (FA) only, 60 mg iron and 2800 µg FA (IFA), or multiple micronutrients (MMs) (15 micronutrients including IFA) from baseline until conception followed by daily prenatal IFA supplements until delivery. Height, weight, mid-upper arm circumference, triceps skinfold, and waist-hip circumference were measured at recruitment and at 1, 2, and 6 to 7 y PP. Body fat was assessed using bioelectric impedance at 6 to 7 y PP (n = 867). Group comparisons were made using analysis of variance or chi-square tests and general linear models for adjusted models. RESULTS: At 6 to 7 y PP, we found significant differences (P < 0.05) by treatment group for mean percent fat (MM: 29.2%; IFA: 27.6%; FA: 27.8%), absolute fat mass (MM: 15.1 kg; IFA: 14.0 kg; FA: 14.3 kg), and prevalence of underweight based on BMI < 18.5 (MM: 5.8%; IFA: 10.3%; FA: 14.3%). Mean BMI and triceps skinfold thickness were higher in the MM group, but these differences were not statistically significant; the differences in absolute fat mass were also attenuated after controlling for body weight. No differences were observed for fat-free mass, prevalence of overweight (BMI >23), or other anthropometric measurements. CONCLUSIONS: Preconception MM supplementation was associated with lower prevalence of underweight and higher percent fat when compared with IFA and/or FA only. Preconception micronutrient interventions may have long-term effects on maternal health and merit further examination. This trial was registered at clinicaltrials.gov as NCT01665378.

Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation in gastric cancer.

BACKGROUND: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. METHODS: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor ß-chain (TCRß), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB). RESULTS: Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRß clonality (inverted Pielou's evenness) increased and TCRß diversity (Pielou's evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023). CONCLUSION: Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.

Structure and Elasticity of Mitochondrial Membranes: A Molecular Dynamics Simulation Study.

Mitochondria are known as the powerhouse of the cell because they produce energy in the form of adenosine triphosphate. They also have other crucial functions such as regulating apoptosis, calcium homeostasis, and reactive oxygen species production. To perform these diverse functions, mitochondria adopt specific structures and frequently undergo dynamic shape changes, indicating that their mechanical properties play an essential role in their functions. To gain a detailed understanding at the molecular level of the structure and mechanical properties of mitochondria, we carry out atomistic molecular dynamics simulations for three inner mitochondrial membranes and three outer mitochondrial membrane models. These models take into account variations in cardiolipin and cholesterol concentrations as well as the symmetry/asymmetry between the two leaflets. Our simulations allow us to calculate various structural quantities and the bending, twisting, and tilting elastic moduli of the membrane models. Our results indicate that the structures of the inner and outer mitochondrial membranes are quite similar and do not depend much on the variation in lipid compositions. However, the bending modulus of the membranes increases with increasing concentrations of cardiolipin or cholesterol but decreases with a membrane asymmetry. Notably, we found that the dipole potential of the membrane increases with an increasing cardiolipin concentration. Finally, possible roles of cardiolipin in regulating ion and proton currents and maintaining the cristate are discussed in some details.

Visible light-induced switching of soft matter materials properties based on thioindigo photoswitches.

Thioindigos are visible light responsive photoswitches with excellent spatial control over the conformational change between their trans- and cis- isomers. However, they possess limited solubility in all conventional organic solvents and polymers, hindering their application in soft matter materials. Herein, we introduce a strategy for the covalent insertion of thioindigo units into polymer main chains, enabling thioindigos to function within crosslinked polymeric hydrogels. We overcome their solubility issue by developing a thioindigo bismethacrylate linker able to undergo radical initiated thiol-ene reaction for step-growth polymerization, generating indigo-containing polymers. The optimal wavelength for the reversible trans-/cis- isomerisation of thioindigo was elucidated by constructing a detailed photochemical action plot of their switching efficiencies at a wide range of monochromatic wavelengths. Critically, indigo-containing polymers display significant photoswitching of the materials' optical and physical properties in organic solvents and water. Furthermore, the photoswitching of thioindigo within crosslinked structures enables visible light induced modulation of the hydrogel stiffness. Both the thioindigo-containing hydrogels and photoswitching processes are non-toxic to cells, thus offering opportunities for advanced applications in soft matter materials and biology-related research.

Recent Computational Advances Regarding Amyloid-ß and Tau Membrane Interactions in Alzheimer's Disease.

The interactions of amyloid proteins with membranes have been subject to many experimental and computational studies, as these interactions contribute in part to neurodegenerative diseases. In this review, we report on recent simulations that have focused on the adsorption and insertion modes of amyloid-ß and tau proteins in membranes. The atomistic-resolution characterization of the conformational changes of these amyloid proteins upon lipid cell membrane and free lipid interactions is of interest to rationally design drugs targeting transient oligomers in Alzheimer's disease.

Concurrent Undernutrition and Overnutrition within Indian Families between 2006 and 2021.

Background: The double burden of malnutrition (DBM), characterized by concurrent undernutrition and overnutrition, is a growing global concern. Families share resources and eating behaviors and programs often target households, yet evidence of the DBM at the family level is scarce. Objectives: This study examined trends and inequality in the intrahousehold DBM in India between 2006 and 2021. Methods: Data were from 3 waves of India's National Family Health Survey (NFHS 2006, 2016, and 2021). We examined 3 types of household member (with children aged <5 y) combinations: mother-child (N = 328,039 across 3 waves), father-child, and parent (mother and father)-child (N = 47,139 for each pair). The DBM was defined as one or more individuals with undernutrition (either wasting or stunting in children or underweight in adults) and one or more overweight individuals within the same household. DBM was examined over time, at national and subnational levels, and by residence and wealth. Results: Nearly all DBM was in the form of an overweight parent and an undernourished weight or stunted child. The prevalence of parent-child DBM increased from 15% in 2006 to 26% in 2021. Father-child pairs experienced the most rapid DBM increase, from 12% in 2006 to 22% in 2021, an 83% increase, driven by increasing overweight among men. In 2021, the DBM was highest in North-Eastern and Southern states, and among relatively rich households from urban areas. The increase in the DBM was faster in rural areas and among poor households compared with that in urban areas and rich households. Urban-rural and rich-poor inequalities in the DBM have decreased over time. Conclusions: The intrahousehold DBM has increased over time, affecting 1 in 4 households in India in 2021. Family-based interventions that can simultaneously address child underweight and parent overweight are required to address India's increasing intrahousehold DBM.

Opportunities and barriers for maternal nutrition behavior change: an in-depth qualitative analysis of pregnant women and their families in Uttar Pradesh, India.

Background: Maternal undernutrition during pregnancy remains a critical public health issue in India. While evidence-based interventions exist, poor program implementation and limited uptake of behavior change interventions make addressing undernutrition complex. To address this challenge, Alive & Thrive implemented interventions to strengthen interpersonal counseling, micronutrient supplement provision, and community mobilization through the government antenatal care (ANC) platform in Uttar Pradesh, India. Objective: This qualitative study aimed to: (1) examine pregnant women's experiences of key nutrition-related behaviors (ANC attendance, consuming a diverse diet, supplement intake, weight gain monitoring, and breastfeeding intentions); (2) examine the influence of family members on these behaviors; and (3) identify key facilitators and barriers that affect behavioral adoption. Methods: We conducted a qualitative study with in-depth interviews with 24 pregnant women, 13 husbands, and 15 mothers-in-law (MIL). We analyzed data through a thematic approach using the Capability-Opportunity-Motivation-Behavior (COM-B) framework. Results: For ANC checkups and maternal weight gain monitoring, key facilitators were frontline worker home visits, convenient transportation, and family support, while the primary barrier was low motivation and lack understanding of the importance of ANC checkups. For dietary diversity, there was high reported capability (knowledge related to the key behavior) and most family members were aware of key recommendations; however, structural opportunity barriers (financial strain, lack of food availability and accessibility) prevented behavioral change. Opportunity ranked high for iron and folic acid supplement (IFA) intake, but was not consistently consumed due to side effects. Conversely, lack of supply was the largest barrier for calcium supplement intake. For breastfeeding, there was low overall capability and several participants described receiving inaccurate counseling messages. Conclusion: Key drivers of maternal nutrition behavior adoption were indicator specific and varied across the capability-opportunity-motivation behavior change spectrum. Findings from this study can help to strengthen future program effectiveness by identifying specific areas of program improvement.

CD38 marks the exhausted CD8+ tissue-resident memory T cells in hepatocellular carcinoma.

Introduction: Despite recent advances in immunotherapy for hepatocellular carcinoma (HCC), the overall modest response rate underscores the need for a better understanding of the tumor microenvironment (TME) of HCC. We have previously shown that CD38 is widely expressed on tumor-infiltrating leukocytes (TILs), predominantly on CD3+ T cells and monocytes. However, its specific role in the HCC TME remains unclear. Methods: In this current study, we used cytometry time-of-flight (CyTOF), bulk RNA sequencing on sorted T cells, and single-cell RNA (scRNA) sequencing to interrogate expression of CD38 and its correlation with T cell exhaustion in HCC samples. We also employed multiplex immunohistochemistry (mIHC) for validating our findings. Results: From CyTOF analysis, we compared the immune composition of CD38-expressing leukocytes in TILs, non-tumor tissue-infiltrating leukocytes (NIL), and peripheral blood mononuclear cells (PBMC). We identified CD8+ T cells as the dominant CD38-expressing TILs and found that CD38 expression was significantly higher in CD8+ TRM in TILs than in NILs. Furthermore, through transcriptomic analysis on sorted CD8+ TRM from HCC tumors, we observed a higher expression of CD38 along with T cell exhaustion genes, including PDCD1 and CTLA4, compared to the circulating memory CD8 T cells from PBMC. This was validated by scRNA sequencing that revealed co-expression of CD38 with PDCD1, CTLA4, and ITGAE (CD103) in T cells from HCC tumors. The protein co-expression of CD38 and PD-1 on CD8+ T cells was further demonstrated by mIHC on HCC FFPE tissues, marking CD38 as a T cell co-exhaustion marker in HCC. Lastly, the higher proportions of CD38+PD-1+ CD8+ T cells and CD38+PD-1+ TRM were significantly associated with the higher histopathological grades of HCC, indicating its role in the aggressiveness of the disease. Conclusion: Taken together, the concurrent expression of CD38 with exhaustion markers on CD8+ TRM underpins its role as a key marker of T cell exhaustion and a potential therapeutic target for restoring cytotoxic T cell function in HCC.

Strengthening Nutrition Interventions during Antenatal Care Improved Maternal Dietary Diversity and Child Feeding Practices in Urban Bangladesh: Results of a Quasi-Experimental Evaluation Study.

BACKGROUND: Bangladesh is urbanizing rapidly, facing challenges of malnutrition, low coverage and poor quality of urban nutrition services. OBJECTIVES: We assessed the effect of integrating maternal, infant, and young child nutrition interventions, delivered at urban Maternal Neonatal and Child Health facilities, on maternal dietary diversity, iron and folic acid (IFA) and calcium consumption, and child feeding practices. METHODS: We used a quasi-experimental design with a nonrandom assignment of 20 health care facilities in Dhaka to intensive and standard service arms. We conducted facility-based observations and community-based surveys at baseline (2020) and endline (2022) (n = 2455 observations and surveys with 1678 pregnant women [PW] or recently delivered women [RDW] at endline). We derived difference-in-difference (DID) estimates, adjusted for characteristics that differed at baseline or endline, and accounted for clustering. RESULTS: Exposure to antenatal care (ANC) was similar in both arms: two-thirds of RDW received ANC during the first trimester and three-fourths received ≥4 ANC checkups. Compared to the standard arm, a higher proportion of PW in the intensive arm received counseling on dietary diversity (DID: 45 percentage points [pp]), and a higher proportion of RDW received IFA (25 pp) and calcium supplementation (19 pp), showed adequate weight gain (44 pp), and recorded appropriate child feeding (27 pp). Improvements were greater in the intensive than the standard arm for the number of food groups consumed (DID: 1.1 food groups) and minimum dietary diversity (23 pp); no effect was observed for IFA and calcium consumption during pregnancy. However, effects were observed for early initiation of (20 pp) and exclusive breastfeeding (45 pp), introduction of solid or semisolid foods (28 pp), and egg and/or flesh food consumption (33 pp) among children. Minimum dietary diversity and acceptable diet remained low in both arms. CONCLUSIONS: Intensifying nutrition in government-aligned health care services delivered by experienced nongovernmental organization-run facilities is a feasible model to address the urban health gap, nutrition services coverage, and improve practices. The trial was registered at clinicaltrials.gov as NCT03882268.

Multistep molecular mechanisms of Aß16-22 fibril formation revealed by lattice Monte Carlo simulations.

As a model of self-assembly from disordered monomers to fibrils, the amyloid-ß fragment Aß16-22 was subject to past numerous experimental and computational studies. Because dynamics information between milliseconds and seconds cannot be assessed by both studies, we lack a full understanding of its oligomerization. Lattice simulations are particularly well suited to capture pathways to fibrils. In this study, we explored the aggregation of 10 Aß16-22 peptides using 65 lattice Monte Carlo simulations, each simulation consisting of 3 × 109 steps. Based on a total of 24 and 41 simulations that converge and do not converge to the fibril state, respectively, we are able to reveal the diversity of the pathways leading to fibril structure and the conformational traps slowing down the fibril formation.

Structure and elasticity of healthy and Alzheimer's disease cell membranes revealed by molecular dynamics simulations.

Interactions of amyloid-ß (Aß) peptides with neuronal membrane are associated with the development of Alzheimer's disease (AD). Ganglioside monosialotetrahexosylganglioside (GM1) lipids have been shown to form clusters that induce the structural conversion of Aß and promote the incorporation of Aß into the membrane via the membrane surface electrical potential. Prior to the onset of AD symptoms, GM1 clusters may not have formed but the concentration of GM1 may have already changed, and our question is whether this early concentration modification affects the structure and mechanical properties of the membrane. Using one model for healthy cell membranes and three models for AD cell membranes, we carry out 2 µs all-atom molecular dynamics simulations for each model to compare the structure and elasticity of the two membrane types. The simulations show that at the physiological concentration, 1%-3%, GM1 does not form clusters. The reduction of the GM1 lipid does not significantly alter the area per lipid, the membrane thickness, and the lipid order parameters of the AD membranes. However, the dipole potential, the bending, and twist moduli are decreased for the AD membranes. We suggest that these changes in the AD membranes are factors that could trigger the interaction and incorporation of Aß to the membranes. Finally, we show that changes in the sphingomyelin lipid concentrations do not affect the membrane structure and elasticity.

Assessing the hidden burden and costs of COVID-19 pandemic in South Asia: Implications for health and well-being of women, children and adolescents.

The COVID-19 pandemic has disproportionately affected vulnerable populations. With its intensity expected to be cyclical over the foreseeable future, and much of the impact estimates still modeled, it is imperative that we accurately assess the impact to date, to help with the process of targeted rebuilding of services. We collected data from administrative health information systems in six South Asian countries (Afghanistan, Bangladesh, Nepal, India, Pakistan and Sri Lanka), to determine essential health services coverage disruptions between January-December 2020, and January-June 2021, compared to the same calendar months in 2019, and estimated the impact of this disruption on maternal and child mortality using the Lives Saved Tool. We also modelled impact of prolonged school closures on continued enrollment, as well as potential sequelae for the cohort of girls who have likely dropped out. Coverage of key maternal and child health interventions, including antenatal care and immunizations, decreased by up to 60%, with the largest disruptions observed between April and June 2020. This was followed by a period of recovery from July 2020 to March 2021, but a reversal of most of these gains in April/May 2021, likely due to the delta variant-fueled surge in South Asia at the same time. We estimated that disruption of essential health services between January 2020 and June 2021 potentially resulted in an additional 19,000 maternal and 317,000 child deaths, an increase of 19% and 13% respectively, compared to 2019. Extended school closures likely resulted in 9 million adolescents dropping out permanently, with 40% likely being from poorest households, resulting in decreased lifetime earnings. A projected increase in early marriages for girls who dropped out could result in an additional 500,000 adolescent pregnancies, 153,000 low birthweight births, and 27,000 additional children becoming stunted by age two years. To date, the increase in maternal and child mortality due to health services disruption has likely exceeded the overall number of COVID-19 deaths in South Asia. The indirect effects of the pandemic were disproportionately borne by the most vulnerable populations, and effects are likely to be long-lasting, permanent and in some cases inter-generational, unless policies aimed at alleviating these impacts are instituted at scale and targeted to reach the poorest of the poor. There are also implications for future pandemic preparedness.

Metastable alpha-rich and beta-rich conformations of small Aß42 peptide oligomers.

Probing the structures of amyloid-ß (Aß) peptides in the early steps of aggregation is extremely difficult experimentally and computationally. Yet, this knowledge is extremely important as small oligomers are the most toxic species. Experiments and simulations on Aß42 monomer point to random coil conformations with either transient helical or ß-strand content. Our current conformational description of small Aß42 oligomers is funneled toward amorphous aggregates with some ß-sheet content and rare high energy states with well-ordered assemblies of ß-sheets. In this study, we emphasize another view based on metastable α-helix bundle oligomers spanning the C-terminal residues, which are predicted by the machine-learning AlphaFold2 method and supported indirectly by low-resolution experimental data on many amyloid polypeptides. This finding has consequences in developing novel chemical tools and to design potential therapies to reduce aggregation and toxicity.