Association of Regular Opioid Use With Incident Dementia and Neuroimaging Markers of Brain Health in Chronic Pain Patients: Analysis of UK Biobank.

OBJECTIVES: We aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients. DESIGN: The primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes. SETTING AND PARTICIPANTS: Dementia-free UK Biobank participants with chronic pain and regular analgesic use. MEASUREMENTS: Chronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively. RESULTS: Prospective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08-1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19-0.71] per 1000 person-years; Wald χ2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07-1.37, Wald χ2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08-1.50, Wald χ2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23-1.67, Wald χ2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes. CONCLUSION: Regular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.

Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes.

The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.

Risk assessment of deep-sea floating offshore wind power projects based on hesitant fuzzy linguistic term set considering trust relationship among experts.

The development of deep-sea floating offshore wind power (FOWP) is the key to fully utilizing water resources to enhance wind resources in the years ahead, and then the project is still in its initial stage, and identifying risks is a crucial step before promoting a significant undertaking. This paper proposes a framework for identifying risks in deep-sea FOWP projects. First, this paper identifies 16 risk criteria and divides them into 5 groups to establish a criteria system. Second, hesitant fuzzy linguistic term set (HFLTS) and triangular fuzzy number (TFN) are utilized to gather and describe the criterion data to ensure the robustness and completeness of the criterion data. Third, extending the method for removal effects of criteria (MEREC) to the HFLTS environment through the conversion of TFNs, under the influence of subjective preference and objective fairness, a weighting method combining analytic network process (ANP) and MEREC is utilized to calculate criteria weights, and the trust relationship and consistency between experts are used to calculate the expert weights to avoid the subjective weighting given by experts arbitrariness. Fourth, the study's findings indicated that the overall risk level of the deep-sea FOWP projects is "medium." Fifth, sensitivity and comparative analyses were conducted to test the reliability of the assessment outcomes. lastly, this research proposes risk management measures for the deep-sea FOWP project's establishment from economic, policy, technology, environment, and management aspects.

HLA-C*07:01 and HLA-DQB1*02:01 protect against white matter hyperintensities and deterioration of cognitive function: A population-based cohort study.

BACKGROUND: Neuroinflammation and aberrant immune regulation are increasingly implicated in the pathophysiology of white matter hyperintensities (WMH), an imaging marker of cerebrovascular pathologies and predictor of cognitive impairment. The role of human leukocyte antigen (HLA) genes, critical in immunoregulation and associated with susceptibility to neurodegenerative diseases, in WMH pathophysiology remains unexplored. METHODS: We performed association analyses between classical HLA alleles and WMH volume, derived from MRI scans of 38 302 participants in the UK Biobank. To identify independent functional alleles driving these associations, we conducted conditional forward stepwise regression and lasso regression. We further investigated whether these functional alleles showed consistent associations with WMH across subgroups characterized by varying levels of clinical determinants. Additionally, we validated the clinical relevance of the identified alleles by examining their association with cognitive function (n = 147 549) and dementia (n = 460 029) in a larger cohort. FINDINGS: Four HLA alleles (DQB1*02:01, DRB1*03:01, C*07:01, and B*08:01) showed an association with reduced WMH volume after Bonferroni correction for multiple comparisons. Among these alleles, DQB1*02:01 exhibited the most significant association (ß = -0.041, 95 % CI: -0.060 to -0.023, p = 1.04 × 10-5). Forward selection and lasso regression analyses indicated that DQB1*02:01 and C*07:01 primarily drove this association. The protective effect against WMH conferred by DQB1*02:01 and C*07:01 persisted in clinically relevant subgroups, with a stronger effect observed in older participants. Carrying DQB1*02:01 and C*07:01 was associated with higher cognitive function, but no association with dementia was found. INTERPRETATION: Our population-based findings support the involvement of immune-associated mechanisms, particularly both HLA class I and class II genes, in the pathogenesis of WMH and subsequent consequence of cognitive functions.

Snoring and risk of dementia: a prospective cohort and Mendelian randomization study.

Background: The association between snoring, a very common condition that increases with age, and dementia risk is controversial. Snoring is linked to obstructive sleep apnoea and cardiometabolic conditions, both of which are associated with an increased risk of dementia. However, snoring also increases with body mass index (BMI), which in late life is linked to lower dementia risk, possibly due to metabolic changes during prodromal dementia. Methods: The prospective cohort study used data from 450,027 UK Biobank participants with snoring measured at baseline (2006 - 2010), and followed up for dementia diagnosis (censored at 2022). Two-sample Mendelian randomization (MR) analysis used summary statistics for genome-wide association studies of Alzheimer's disease (AD) (n = 94,437; cases = 35,274) and snoring (n = 408,317; snorers = 151,011). Results: During a median follow-up of 13.5 years, 7,937 individuals developed dementia. Snoring was associated with an 8% lower risk of all-cause dementia (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.88 to 0.97) and AD (HR 0.92; 95% CI 0.86 to 0.99). The association was stronger in older individuals, APOE ε4 allele carriers, and during shorter follow-up periods. MR analyses suggested no causal effect of snoring on AD, however, genetic liability to AD was associated with a lower risk of snoring. Multivariable MR indicated that the effect of AD on snoring was primarily driven by BMI. Conclusions: The phenotypic association between snoring and lower dementia risk likely stems from reverse causation, with genetic predisposition to AD associated with reduced snoring. This may be driven by weight loss in prodromal AD.

Nonagricultural emissions enhance dimethylamine and modulate urban atmospheric nucleation.

Gas-phase dimethylamine (DMA) has recently been identified as one of the most important vapors to initiate new particle formation (NPF), even in China's polluted atmosphere. Nevertheless, there remains a fundamental need for understanding the atmospheric life cycle of DMA, particularly in urban areas. Here we pioneered large-scale mobile observations of the DMA concentrations within cities and across two pan-region transects of north-to-south (∼700 km) and west-to-east (∼2000 km) in China. Unexpectedly, DMA concentrations (mean ± 1σ) in South China with scattered croplands (0.018 ± 0.010 ppbv, 1 ppbv=10-9 L/L) were over three times higher than those in the north with contiguous croplands (0.005 ± 0.001 ppbv), suggesting that nonagricultural activities may be an important source of DMA. Particularly in non-rural regions, incidental pulsed industrial emissions led to some of the highest DMA concentration levels in the world (>2.3 ppbv). Besides, in highly urbanized areas of Shanghai, supported by direct source-emission measurements, the spatial pattern of DMA was generally correlated with population (R2 = 0.31) due to associated residential emissions rather than vehicular emissions. Chemical transport simulations further show that in the most populated regions of Shanghai, residential DMA emissions can contribute for up to 78% of particle number concentrations. Shanghai is a case study for populous megacities, and the impacts of nonagricultural emissions on local DMA concentration and nucleation are likely similar for other major urban regions globally.

Household Water Access, Dietary Diversity and Nutritional Status among Preschoolers in Poor, Rural Areas of Central and Western China.

Poor child feeding and childhood malnutrition are major public health problems in rural central and western China, with little evidence about their environmental determinants. This study aimed to investigate whether household water access is associated with dietary diversity and nutritional outcomes. We analyzed the cross-sectional data of 3727 children aged 6 to 59 months in rural central and western China, applying multivariate linear and logistic models to estimate the effect of water access on children's anthropometric indices, hemoglobin, and dietary diversity. We found that unimproved water access was linked to a lower likelihood of achieving dietary diversity (OR = 0.65, 95% CI 0.44 to 0.98, p = 0.039); lower height-for-age z-score (ß = −0.34, 95% CI −0.49 to −0.19, p < 0.001) and hemoglobin concentration (ß = −2.78, 95% CI −5.16 to −0.41, p = 0.022); higher odds of stunting (OR = 1.50, 95% CI 1.01 to 2.25, p = 0.047) and anemia (OR = 1.34, 95% CI 1.02 to 1.77, p = 0.037). The associations between water access and nutritional outcomes were not explained by dietary diversity and were stronger in children who did not receive iron supplementation. These findings provide evidence for designing water-based nutritional interventions in China.

Association Between Violent Discipline at Home and Risk of Illness and Injury in Children: Findings From a Cross-sectional Study in Rural Western China.

To estimate the prevalence of violent discipline at home against young children, and to explore the potential association between violent discipline at home and multifaceted health risks in children. A community-based cross-sectional survey was conducted in twenty rural counties of weight provinces in western China. The information about child neglect and socio-demographic factors, exposure to different forms of violent discipline at home and four health outcomes was collected by face-to-face interview. Before analysis, the included interviews were weighted by the double-weighted comprehensive weighting. The proportion of children reported by primary caregivers to have experienced different forms of violent discipline by gender were calculated. To adjust the clustering effect of the survey design, two-level univariate and multivariate logistic regression models were constructed to evaluate the potential association between a child's exposure to violent discipline at home and risk of suffering from diarrhea, fever, cough and injury. A total of 3,682 weighted interviews were finally included in the analysis. The prevalence of any violent discipline, psychological aggression, any physical punishment and severe physical punishment were 76.4%, 57.5%, 68.3% and 14.1%, respectively. In multivariate analysis, after adjusting for clustering, there was still a positive association between a child's exposure to psychological aggression and risk of diarrhea (adjusted OR: 1.47, 95%CI: 1.14-1.90) and injury (adjusted OR: 1.95, 95%CI: 1.36-2.80); a child's exposure to any physical punishment and risk of diarrhea (adjusted OR: 1.36, 95%CI: 1.04-1.77), cough (adjusted OR: 1.37, 95%CI: 1.14-1.66), and injury (adjusted OR: 2.05, 95%CI: 1.37-3.06); and a child's exposure to severe physical punishment and risk of injury (adjusted OR: 2.07, 95%CI: 1.41-3.05). Considering that using violent discipline at home is prevalent in rural western China, and it could threaten young children's health, effective measures to prevent young children from violent discipline are urgently needed.

Intimate Partner Violence against Women Living in Inadequate Conditions in Sub-Saharan Africa: A Meta-Analysis of Demographic and Health Survey Data.

Intimate partner violence (IPV) against women is a major public health problem and is widespread in sub-Saharan Africa (SSA). However, little is known about its environmental determinants. This study aimed to investigate whether inadequate living conditions are associated with IPV victimization in women in SSA. We analyzed cross-sectional data for 102,714 women in 25 SSA countries obtained from the Demographic and Health Surveys Program. Logistic regression was used to estimate the country-specific effects of inadequate living conditions (housing with at least one of four characteristics of unimproved water, unimproved sanitation, insufficient space, and unfinished materials) on multiple forms of IPV. Random effects meta-analysis was used to combined the country-specific estimates. We found an association between inadequate living conditions and a higher likelihood of experiencing any (OR = 1.12, 95% CI 1.03 to 1.23, p = 0.012), sexual (OR = 1.18, 95% CI 1.05 to 1.34, p = 0.008), emotional (OR = 1.12, 95% CI 1.02 to 1.23, p = 0.023), and physical (OR = 1.15, 95% CI 1.03 to 1.28, p = 0.010) IPV. The associations were stronger for rural and less-educated women. These findings suggest that future research to establish a causal link between living conditions and IPV and to elucidate the underlying pathways is crucial to design IPV interventions in SSA.

Maternal depressive symptoms and early childhood development: the role of mother-child interactions among mother-child dyads in rural areas of Central and Western China.

BACKGROUND: The associations among maternal depressive symptoms (MDS), mother-child interactions and early child development are poorly understood. This study aimed to explore the role of mother-child interactions on the associations between MDS and child development. METHODS: A cross-sectional study with a multistage sampling method was conducted in rural areas of Central and Western China. MDS, child development outcomes (communication, gross motor function, fine motor function, problem solving and personal social skills) and mother-child interactions were assessed by The Edinburgh Postpartum Depression Scale, the Chinese version of the Ages and Stages Questionnaires and the Multiple Indicator Cluster Surveys, respectively. Regression-based statistical mediation and moderation were conducted using the PROCESS macro for SPSS. RESULTS: A total of 2,548 participants (mothers: 1,274; children: 1,274) were included in our analyses. MDS was negatively associated with child development outcomes and mother-child interactions partly mediated these associations. The proportion of the mediating effect of mother-child interactions was 7.7% for communication, 8.2% for gross motor, 10.3% for fine motor, 10.1% for problem-solving and 9.5% for personal social domains. In addition, the interaction effects of MDS and mother-child interactions on the communication domain were significant (ß = 0.070, 95% CI 0.016, 0.124; p = 0.011). The associations between MDS and child communication abilities were weaker at the high level (simple slope = -0.019, t =  - 0.458, p = 0.647) of mother-child interactions than at the mean level (simple slope = -0.089, t =  - 3.190, p = 0.002) and the low level (simple slope = -0.158, t =  - 4.231, p < 0.001). Similar moderating effects were not observed in the other child development outcomes. CONCLUSION: Our results suggest the important role of mother-child interactions on the associations between MDS and early childhood development. Due to the cross-sectional design of this study, these associations require further investigation in prospective studies.

Housing environment and early childhood development in sub-Saharan Africa: A cross-sectional analysis.

BACKGROUND: The influence of the safety and security of environments on early childhood development (ECD) has been under-explored. Although housing might be linked to ECD by affecting a child's health and a parent's ability to provide adequate care, only a few studies have examined this factor. We hypothesized that housing environment is associated with ECD in sub-Saharan Africa (SSA). METHODS AND FINDINGS: From 92,433 children aged 36 to 59 months who participated in Multiple Indicator Cluster Survey (MICS) in 20 SSA countries, 88,271 were tested for cognitive and social-emotional development using the Early Childhood Development Index (ECDI) questionnaire and were thus included in this cross-sectional analysis. Children's mean age was 47.2 months, and 49.8% were girls. Children were considered developmentally on track in a certain domain if they failed no more than 1 ECDI item in that domain. In each country, we used conditional logistic regression models to estimate the association between improved housing (housing with finished building materials, improved drinking water, improved sanitation facilities, and sufficient living area) and children's cognitive and social-emotional development, accounting for contextual effects and socioeconomic factors. Estimates from each country were pooled using random-effects meta-analyses. Subgroup analyses were conducted by the child's gender, maternal education, and household wealth quintiles. On-track cognitive development was associated with improved housing (odds ratio [OR] = 1.15, 95% CI 1.06 to 1.24, p < 0.001), improved drinking water (OR = 1.07, 95% CI 1.00 to 1.14, p = 0.046), improved sanitation facilities (OR = 1.15, 95% CI 1.03 to 1.28, p = 0.014), and sufficient living area (OR = 1.06, 95% CI 1.01 to 1.10, p = 0.018). On-track social-emotional development was associated with improved housing only in girls (OR = 1.14, 95% CI 1.04 to 1.25, p = 0.006). The main limitations of this study included the cross-sectional nature of the datasets and the use of the ECDI, which lacks sensitivity to measure ECD outcomes. CONCLUSIONS: In this study, we observed that improved housing was associated with on-track cognitive development and with on-track social-emotional development in girls. These findings suggest that housing improvement in SSA may be associated not only with benefits for children's physical health but also with broader aspects of healthy child development.

Association of iron supplementation and deworming with early childhood development: analysis of Demographic and Health Surveys in ten low- and middle-income countries.

PURPOSE: We assessed the associations of iron supplementation and deworming separately or combined with improved early childhood development (ECD) status. METHODS: Cross-sectional data were analyzed for 29,729 children aged 36-59 months surveyed using the Demographic and Health Surveys in ten low- and middle-income countries, where iron supplementation and deworming are recommended by the World Health Organization. In each country, we estimated linear regression models for the effects of iron supplementation and deworming individually or combined on the Early Childhood Development Index (ECDI) z score, and whether this association differed between various ECD domains and the sex and residence of the child. Estimates were pooled using random-effects meta-analyses. RESULTS: Compared with receiving neither of the two interventions, iron supplementation plus deworming was associated with an increased ECDI z score (ß = 0.13, 95% confidence interval (CI) 0.03-0.22, p = 0.009), particularly in rural residences. However, iron supplementation and deworming, individually, were not associated with the ECDI z score. Iron supplementation plus deworming was associated with higher odds of on-track development in literacy-numeracy (OR = 1.57, 95% CI 1.24-2.01, p < 0.001) and learning domains (OR = 1.27, 95% CI 1.09-1.48, p = 0.003), but not with development in the social-emotional and physical domains. CONCLUSION: Iron supplementation plus deworming, particularly for populations who are more susceptible to iron deficiency and intestinal worm infections, could be an important intervention for improving ECD. These findings may inform the argument for the necessity of implementing iron supplementation and deworming for preschool-age children.

Association between Household Crowding and Violent Discipline and Neglect of Children: Analysis of Multiple Indicator Cluster Surveys in 26 Low- and Middle-Income Countries.

The influence of household crowding on physical and mental health has been well documented. However, research on the influence of household crowding on violent discipline and neglect of children is scarce. Therefore, we aimed to investigate whether household crowding was associated with violent discipline and neglect of children in low- and- middle-income countries (LMICs). Cross-sectional data for 280,005 and 73,030 children in 26 LMICs surveyed using the Multiple Indicator Cluster Survey were analyzed for (1) violent discipline and (2) neglect, respectively. In each country, we used logistic regression models to estimate the effects of household crowding on multiple forms of violent discipline and stimulation activities (as a proxy of the level of child neglect). Estimates were pooled using random effects meta-analyses. After adjusting for confounding variables, household crowding was associated with higher odds of any violent discipline (odds ratio (OR) = 1.09, 95% CI 1.03 to 1.15, p = 0.002) and lower odds of engaging in four or more stimulation activities (OR = 0.88, 95% CI 0.83 to 0.94, p < 0.001). The associations were stronger for urban children and children living in low- and lower-middle-income countries. The findings suggest that screenings and interventions aimed at reducing the effects of household crowding might be effective in preventing and controlling violent discipline and neglect of children in LMICs.

Gestational Diabetes Mellitus: Predictive Value of Fetal Growth Measurements by Ultrasonography at 22-24 Weeks: A Retrospective Cohort Study of Medical Records.

Early intervention of gestational diabetes mellitus (GDM) is effective in reducing pregnancy disorders. Fetal growth, measured by routine ultrasound scan a few weeks earlier before GDM diagnosis, might be useful to identify women at high risk of GDM. In the study, generalized estimating equations were applied to examine the associations between ultrasonic indicators of abnormal fetal growth at 22-24 weeks and the risk of subsequent GDM diagnosis. Of 44,179 deliveries, 8324 (18.8%) were diagnosed with GDM between 24 and 28 weeks. At 22-24 weeks, fetal head circumference (HC) < 10th, fetal femur length (FL) < 10th, and estimated fetal weight (EFW) < 10th percentile were associated with 13% to 17% increased risks of maternal GDM diagnosis. Small fetal size appeared to be especially predictive of GDM among women who were parous. Fetal growth in the highest decile of abdominal circumference (AC), HC, FL and EFW was not associated with risk of subsequent GDM. The observed mean difference in fetal size across gestation by GDM was small; there was less than 1 mm difference for AC, HC, and FL, and less than 5 g for EFW before 24 weeks. Despite similar mean fetal growth among women who were and were not later diagnosed with GDM, mothers with fetuses in the lowest decile of HC, FL and EFW at 22-24 weeks tended to have higher risk of GDM.

Socio-emotional challenges and development of children left behind by migrant mothers.

BACKGROUND: With great economic development and rapid urbanization in China, left-behind children whose parents migrate to big cities for job has become a large special population which requires more attention. The present study aims to explore the specific influence of migrant mothers on early child development, especially on social-emotional problems. METHODS: The data of this study was obtained from a cross-sectional study in 8 counties of central and western rural China. Development status of 1880 children aged <60 months were assessed by Ages & Stages Questionnaire-Chinese Edition (ASQ) and the Ages and Stages Questionnaire: Social Emotional-Chinese Edition (ASQ: SE). Multivariate logistic regressions were used to analyze the association between being left behand by migrant mothers and developmental problems in various domains, while adjusting socio-demographic, socio-economic and perinatal co-variates, and effect modification analysis were conducted to explore the effect of age, gender and birth order. RESULTS: Children left behind by migrant mothers were more likely to have overall suspected developmental delay (odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.13-1.35), developmental delay in personal social domain (OR = 1.55, 95% CI = 1.17-2.04) and socio-emotional delay compared with those living with their own mothers (OR = 1.49, 95% CI = 1.11-2.00) after adjusting for potential confounders. Additionally, girls increased the odds of social-emotional problems among children being left behind by migrating mother (P for interaction = 0.037). CONCLUSIONS: The study concluded that children left behind by migrant mothers were more likely to have suspected developmental delay compared with their peers living with mothers, especially on social emotional development. Future intervention is needed for this special population and should pay more attention to girls.

Inequality in measles vaccination coverage in the "big six" countries of the WHO South-East Asia region.

The "big six" countries (Bangladesh, India, Indonesia, Myanmar, Nepal, and Thailand) in the World Health Organization South-East Asia Region (WHO SEAR) are currently facing severe challenges in measles elimination and consequent childhood mortality reduction, with inadequacies and inequalities in the coverage of the measles-containing-vaccine first-dose (MCV1) being major obstacles. However, these issues of inequality in MCV1 coverage have not yet been systematically examined. We used data from the latest Demographic and Health Surveys and Multiple Indicator Cluster Surveys. To provide a comprehensive picture of existing MCV1 coverage gaps, data were disaggregated by geographic location, as well as by socioeconomic and nutritional dimensions. National MCV1 coverage ranged from 77% in Myanmar to 92% in Thailand. Only nine of the 104 sub-national districts had achieved the 95% MCV1 coverage goal as set by the WHO. Geographic inequalities were more pronounced in countries with lower coverage levels. Areas in clusters with poor MCV1 coverage performances as well as disadvantaged socioeconomic profiles require increased attention. Inequalities were evident in all countries, except Thailand, and were more pronounced in the sectors of wealth, education, antenatal care (ANC) status, and vitamin A supplementation (VAS) when compared against the areas of gender and urban/rural residence. Wealth-related inequality in Bangladesh, education-related inequality in Indonesia, ANC-related inequalities in Myanmar and Nepal, and VAS-related inequalities in Indonesia and Myanmar were all noteworthy. Equity-oriented changes in policies focusing on health promotion and integrated interventions among disadvantaged populations need to be implemented in order to increase MCV1 coverage and reduce childhood mortality.

The Inflammatory Transcription Factor C/EBPß Plays a Critical Role in Cardiac Fibroblast Differentiation and a Rat Model of Cardiac Fibrosis Induced by Autoimmune Myocarditis.

The aim of the present study was to investigate the mechanisms of CCAAT/enhancer-binding protein ß (C/EBPß) in cardiac myofibroblast (CMF) differentiation and in a rat model of cardiac fibrosis induced by experimental autoimmune myocarditis (EAM).In vitro studies performed in primary neonatal rat CMF revealed that silencing of C/EBPß expression (via lentiviral mediated shRNA strategies) was sufficient to reduce C/EBPß mRNA and protein levels as well as to decrease the expressions of actin cytoskeletal proteins, cofilin, and filamin A (FLNA). TGFß increased IL-1ß, IL-6 and TNF-a production in cardiac fibroblasts (CF), while C/EBPß knockdown reduced the secretion of these inflammatory mediators. In vivo studies performed in rats exhibiting EAM revealed that lentiviral-mediated silencing of C/EBPß was sufficient to reduce the expression of C/EBPß as well as inflammation and fibrosis in the hearts of EAM rats, when compared to controls. Echocardiography further revealed that C/EBPß knockdown was sufficient to significantly improve cardiac dimensions and function in EAM rats. Immunohistochemical results showed that C/EBPß knockdown attenuated the expression of C/EBPß protein as well as the expressions of collagen I, collagen III, MMP-2, MMP-9, and α-SMA in heart tissue sections from rats in the EAM + Lenti-shC/EBPß group.Strategies targeted at inhibiting C/EBPß expression can be potentially exploited to regulate cofilin and FLNA expression, thereby regulating actin polymerization/depolymerization, cytoskeleton rearrangement, and CF differentiation into CMF and the production of inflammatory cytokines. C/EBPß knock down reduces the degree of inflammation-mediated myocardial fibrosis in a rat model of EAM.