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.

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.

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.

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.

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.

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.

Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC.

BACKGROUND AND AIMS: Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the hypoxic TME of HCC remains to be elucidated. APPROACH AND RESULTS: We analyzed the immune landscapes of hypoxia-low and hypoxia-high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses. The mechanisms of immunosuppression in immune subsets of interest were further explored using in vitro hypoxia assays. Regulatory T cells (Tregs) and a number of immunosuppressive myeloid subsets, including M2 macrophages and human leukocyte antigen-DR isotype (HLA-DRlo ) type 2 conventional dendritic cell (cDC2), were found to be significantly enriched in hypoxia-high tumor regions. On the other hand, the abundance of active granzyme Bhi PD-1lo CD8+ T cells in hypoxia-low tumor regions implied a relatively active immune landscape compared with hypoxia-high regions. The up-regulation of cancer-associated genes in the tumor tissues and immunosuppressive genes in the tumor-infiltrating leukocytes supported a highly pro-tumorigenic network in hypoxic HCC. Chemokine genes such as CCL20 (C-C motif chemokine ligand 20) and CXCL5 (C-X-C motif chemokine ligand 5) were associated with recruitment of both Tregs and HLA-DRlo cDC2 to hypoxia-high microenvironments. The interaction between Tregs and cDC2 under a hypoxic TME resulted in a loss of antigen-presenting HLA-DR on cDC2. CONCLUSIONS: We uncovered the unique immunosuppressive landscapes and identified key immune subsets enriched in hypoxic HCC. In particular, we identified a potential Treg-mediated immunosuppression through interaction with a cDC2 subset in HCC that could be exploited for immunotherapies.

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.

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.

Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo, and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aß, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research, respectively, for many years.

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.

Disassembly of Amyloid Fibril with Infrared Free Electron Laser.

Amyloid fibril causes serious amyloidosis such as neurodegenerative diseases. The structure is composed of rigid ß-sheet stacking conformation which makes it hard to disassemble the fibril state without denaturants. Infrared free electron laser (IR-FEL) is an intense picosecond pulsed laser that is oscillated through a linear accelerator, and the oscillation wavelengths are tunable from 3 µm to 100 µm. Many biological and organic compounds can be structurally altered by the mode-selective vibrational excitations due to the wavelength variability and the high-power oscillation energy (10-50 mJ/cm2). We have found that several different kinds of amyloid fibrils in amino acid sequences were commonly disassembled by the irradiation tuned to amide I (6.1-6.2 µm) where the abundance of ß-sheet decreased while that of α-helix increased by the vibrational excitation of amide bonds. In this review, we would like to introduce the IR-FEL oscillation system briefly and describe combination studies of experiments and molecular dynamics simulations on disassembling amyloid fibrils of a short peptide (GNNQQNY) from yeast prion and 11-residue peptide (NFLNCYVSGFH) from ß2-microglobulin as representative models. Finally, possible applications of IR-FEL for amyloid research can be proposed as a future outlook.

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.

Specificity Matters: Unpacking Impact Pathways of Individual Interventions within Bundled Packages Helps Interpret the Limited Impacts of a Maternal Nutrition Intervention in India.

BACKGROUND: To address gaps in coverage and quality of nutrition services, Alive & Thrive (A&T) strengthened the delivery of maternal nutrition interventions through government antenatal care (ANC) services in Uttar Pradesh, India. The impact evaluation of the A&T interventions compared intensive ANC (I-ANC) with standard ANC (S-ANC) areas and found modest impacts on micronutrient supplementation, dietary diversity, and weight-gain monitoring. OBJECTIVES: This study examined intervention-specific program impact pathways (PIPs) and identified reasons for limited impacts of the A&T maternal nutrition intervention package. METHODS: We used mixed methods: frontline worker (FLW) surveys (n = ∼500), counseling observations (n = 407), and qualitative in-depth interviews with FLWs, supervisors, and block-level staff (n = 59). We assessed 7 PIP domains: training and materials, knowledge, supportive supervision, supply chains, data use, service delivery, and counseling. RESULTS: Exposure to training improved in both I-ANC and S-ANC areas with more job aids used in I-ANC compared with S-ANC (90% compared with 70%), but gaps remained for training content and refresher trainings. FLWs' knowledge improvement was higher in I-ANC than S-ANC (22-36 percentage points), but knowledge of micronutrient supplement benefits and recommended foods was insufficient (<50%). Most FLWs received supervision (>90%), but supportive supervision was limited by staff vacancies and competing work priorities. Supplies of iron-folic acid and calcium supplements were low in both areas (30-50% stock-outs). Use of monitoring data during review meetings was higher in I-ANC than S-ANC (52% compared with 36%) but was constrained by time, understanding, and data quality. Service provision improved in both I-ANC and S-ANC areas, but counseling on supplement benefits and weight-gain monitoring was low (30-40%). CONCLUSIONS: Systems-strengthening efforts improved maternal nutrition interventions in ANC, but gaps remained. Taking an intervention-specific perspective to the PIP analysis in this package of services was critical to understand how common and specific barriers influenced overall program impact.

Elastic moduli of normal and cancer cell membranes revealed by molecular dynamics simulations.

Recent studies indicate that there are mechanical differences between normal cells and cancer cells. Because the cell membrane takes part in a variety of vital processes, we test the hypothesis of whether or not two fundamental alterations in the cell membrane, i.e., the overexpression of phosphatidylserine lipids in the outer leaflet and a reduction in cholesterol concentration, could cause the softening in cancer cells. Adopting ten models of normal and cancer cell membranes, we carry out 1 µs all-atom molecular dynamics simulations to compare the structural properties and elasticity properties of two membrane types. We find that the overexpression of the phosphatidylserine lipids in the outer leaflet does not significantly alter the area per lipid, the membrane thickness, the lipid order parameters and the elasticity moduli of the cancer membranes. However, a reduction in the cholesterol concentration leads to clear changes in those quantities, especially decreases in the bending, tilt and twist moduli. This implies that the reduction of cholesterol concentration in the cancer membranes could contribute to the softening of cancer cells.

Molecular dynamics simulation of cancer cell membrane perforated by shockwave induced bubble collapse.

It has been widely accepted that cancer cells are softer than their normal counterparts. This motivates us to propose, as a proof-of-concept, a method for the efficient delivery of therapeutic agents into cancer cells, while normal cells are less affected. The basic idea of this method is to use a water jet generated by the collapse of the bubble under shockwaves to perforate pores in the cell membrane. Given a combination of shockwave and bubble parameters, the cancer membrane is more susceptible to bending, stretching, and perforating than the normal membrane because the bending modulus of the cancer cell membrane is smaller than that of the normal cell membrane. Therefore, the therapeutic agent delivery into cancer cells is easier than in normal cells. Adopting two well-studied models of the normal and cancer membranes, we perform shockwave induced bubble collapse molecular dynamics simulations to investigate the difference in the response of two membranes over a range of shockwave impulse 15-30 mPa s and bubble diameter 4-10 nm. The simulation shows that the presence of bubbles is essential for generating a water jet, which is required for perforation; otherwise, pores are not formed. Given a set of shockwave impulse and bubble parameters, the pore area in the cancer membrane is always larger than that in the normal membrane. However, a too strong shockwave and/or too large bubble results in too fast disruption of membranes, and pore areas are similar between two membrane types. The pore closure time in the cancer membrane is slower than that in the normal membrane. The implications of our results for applications in real cells are discussed in some details. Our simulation may be useful for encouraging future experimental work on novel approaches for cancer treatment.

Findings from a tandem clinician leadership intervention for emergency department cardiac arrest care during the COVID-19 pandemic.

INTRODUCTION: Cardiopulmonary arrest (CPA) care in the Emergency Department (ED) has had to be modified during the coronavirus disease (COVID-19) pandemic. Scarce literature exists on comfort of clinicians (defined as physicians, nurses & advanced practice providers-APP's) in these new roles and their perceived understanding of new algorithms. METHODS: Routine CPA care in our ED was modified during the COVID-19 pandemic. This involved clinicians in shared leadership roles alongside COVID-19 specific changes to CPA algorithms. The new protocol was operationalized through a two-step educational intervention involving didactic education and in-situ simulations. Univariate analyses using student's t-test assessed effectiveness of this educational intervention with clinician comfort as team leaders and perceived knowledge as primary outcomes on a scale of 1 (strongly disagree) to 5 (strongly agree). Subgroup analysis across physicians (attending & resident), nurses & APP's were also undertaken with an alpha of 0.05, and p values <0.05 were considered statistically significant. Secondary outcomes of task saturation, procedural safety and error prevention were also analyzed. RESULTS: Across 83 of 95 total participants, our primary outcome of clinician comfort in the team leader role improved from a mean value of 3.41 (SD: 1.23) pre-intervention to 4.11 (SD: 0.88) with a p-value <0.001 post intervention. Similar and statistically significant findings in clinician comfort were noted across all subgroups except attending physicians and APP's. Perceived knowledge increased from a mean value of 3.54 (SD: 1.06) pre-intervention to a mean value of 4.24 (SD: 0.67) with a p-value <0.001 post intervention. Similar and statistically significant findings in perceived knowledge were noted across all subgroups except APP's. Responses were registered in either the strongly agree or agree category with regards to task saturation (89%), procedural safety (93%) and error prevention (71%) across all clinicians post intervention. CONCLUSION: Our pilot investigation of the effectiveness of an educational intervention of a novel CPA protocol in the ED during the COVID-19 pandemic reached statistical significance with regards to clinician comfort in shared leadership roles and perceived knowledge. These findings suggest that the protocol is rapidly teachable, usable and can be efficiently disseminated across ED clinicians of varying experience, especially in pandemic settings. Further work regarding effectiveness of this new protocol in real life cardiac arrest scenarios is warranted.

Effect of Cholesterol Molecules on Aß1-42 Wild-Type and Mutants Trimers.

Alzheimer's disease displays aggregates of the amyloid-beta (Aß) peptide in the brain, and there is increasing evidence that cholesterol may contribute to the pathogenesis of the disease. Though many experimental and theoretical studies have focused on the interactions of Aß oligomers with membrane models containing cholesterol, an understanding of the effect of free cholesterol on small Aß42 oligomers is not fully established. To address this question, we report on replica exchange with a solute tempering simulation of an Aß42 trimer with cholesterol and compare it with a previous replica exchange molecular dynamics simulation. We show that the binding hot spots of cholesterol are rather complex, involving hydrophobic residues L17-F20 and L30-M35 with a non-negligible contribution of loop residues D22-K28 and N-terminus residues. We also examine the effects of cholesterol on the trimers of the disease-causing A21G and disease-protective A2T mutations by molecular dynamics simulations. We show that these two mutations moderately impact cholesterol-binding modes. In our REST2 simulations, we find that cholesterol is rarely inserted into aggregates but rather attached as dimers and trimers at the surface of Aß42 oligomers. We propose that cholesterol acts as a glue to speed up the formation of larger aggregates; this provides a mechanistic link between cholesterol and Alzheimer's disease.

Gaps in the implementation and uptake of maternal nutrition interventions in antenatal care services in Bangladesh, Burkina Faso, Ethiopia and India.

Antenatal care (ANC) is the largest health platform globally for delivering maternal nutrition interventions (MNIs) to pregnant women. Yet, large missed opportunities remain in nutrition service delivery. This paper examines how well evidence-based MNIs were incorporated in national policies and programs in Bangladesh, Burkina Faso, Ethiopia and India. We compared the nutrition content of ANC protocols against global recommendations. We used survey data to elucidate the coverage of micronutrient supplementation, weight gain monitoring, dietary and breastfeeding counselling. We reviewed literature, formative research and program assessments to identify barriers and enabling factors of service provision and maternal nutrition practices. Nutrition information in national policies and protocols was often fragmented, incomplete and did not consistently follow global recommendations. Nationally representative data on MNIs in ANC was inadequate, except for iron and folic acid supplementation. Coverage data from subnational surveys showed similar patterns of strengths and weaknesses. MNI coverage was consistently lower than ANC coverage with the lowest coverage of weight gain monitoring and variable coverage of dietary and breastfeeding counselling. Key common factors associated with coverage were micronutrient supply disruptions; suboptimal counselling on maternal diet, weight gain, and breastfeeding; and limited or no record keeping. Adherence of women to micronutrient supplementation and dietary recommendations was low and associated with late and too few ANC contacts, poor maternal knowledge and self-efficacy, and insufficient family and community support. Models of comprehensive nutrition protocols and health systems that deliver maternal nutrition services in ANC are urgently needed along with national data systems to track progress.

Using scenario-based assessments to examine the feasibility of integrating preventive nutrition services through the primary health care system in Bangladesh.

The National Nutrition Services of Bangladesh aims to deliver nutrition services through the primary health care system. Little is known about the feasibility of reshaping service delivery to close gaps in nutrition intervention coverage and utilization. We used a scenario-based feasibility testing approach to assess potential implementation improvements to strengthen service delivery. We conducted in-depth interviews with 31 service providers and 12 policymakers, and 5 focus group discussions with potential beneficiaries. We asked about the feasibility of four hypothetical scenarios for preventive and promotive nutrition service delivery: community-based events (CBE) for pregnant women, well-child services integrated into immunization contacts; CBE for well-children, and well-child visits at facilities. Opinions on service delivery platforms were mixed; some recommended new platforms, but others suggested strengthening existing delivery points. CBE for pregnant women was perceived as feasible, but workforce shortages emerged as a key barrier. Challenges such as equipment portability, upset children and a fast-moving service environment suggested low feasibility of integrating nutrition into outreach immunization contacts. In contrast, CBE and facility-based well-child visits emerged as feasible options, conditional on having the necessary workforce, structural readiness and budget support. On the demand side, enabling factors include using interpersonal communication and involving community leaders to increase awareness, organizing events at a convenient time and place for both providers and beneficiaries, and incentives for beneficiaries to encourage participation. In conclusion, integrating preventive and promotive nutrition services require addressing current challenges in the health system, including human resource and logistic gaps, and investing in creating demand for preventive services.

COVID-19 Disrupted Provision and Utilization of Health and Nutrition Services in Uttar Pradesh, India: Insights from Service Providers, Household Phone Surveys, and Administrative Data.

BACKGROUND: The coronavirus (COVID-19) pandemic may substantially affect health systems, but little primary evidence is available on disruption of health and nutrition services. OBJECTIVES: This study aimed to 1) determine the extent of disruption in provision and utilization of health and nutrition services induced by the pandemic in Uttar Pradesh, India; and 2) identify how adaptations were made to restore service provision in response to the pandemic. METHODS: We conducted longitudinal surveys with frontline workers (FLWs, n = 313) and mothers of children <2 y old (n = 659) in December 2019 (in-person) and July 2020 (by phone). We also interviewed block-level managers and obtained administrative data. We examined changes in service provision and utilization using Wilcoxon matched-pairs signed-rank tests. RESULTS: Compared with prepandemic, service provision reduced substantially during lockdown (83-98 percentage points, pp), except for home visits and take-home rations (∼30%). Most FLWs (68%-90%) restored service provision in July 2020, except for immunization and hot cooked meals (<10%). Administrative data showed similar patterns of disruption and restoration. FLW fears, increased workload, inadequate personal protective equipment (PPE), and manpower shortages challenged service provision. Key adaptations made to provide services were delivering services to beneficiary homes (∼40%-90%), social distancing (80%), and using PPE (40%-50%) and telephones for communication (∼20%). On the demand side, service utilization reduced substantially (40-80 pp) during the lockdown, but about half of mothers received home visits and food supplementation. Utilization for most services did not improve after the lockdown, bearing the challenges of limited travel (30%), nonavailability of services (26%), and fear of catching the virus when leaving the house (22%) or meeting service providers (14%). CONCLUSIONS: COVID-19 disrupted the provision and use of health and nutrition services in Uttar Pradesh, India, despite adaptations to restore services. Strengthening logistical support, capacity enhancement, performance management, and demand creation are needed to improve service provision and utilization during and post-COVID-19.