Gene-regulation modules in nonalcoholic fatty liver disease revealed by single-nucleus ATAC-seq.

We investigated the progression of nonalcoholic fatty liver disease from fatty liver to steatohepatitis using single-nucleus and bulk ATAC-seq on the livers of rats fed a high-fat diet (HFD). Rats fed HFD for 4 wk developed fatty liver, and those fed HFD for 8 wk further progressed to steatohepatitis. We observed an increase in the proportion of inflammatory macrophages, consistent with the pathological progression. Utilizing machine learning, we divided global gene regulation into modules, wherein transcription factors within a module could regulate genes within the same module, reaffirming known regulatory relationships between transcription factors and biological processes. We identified core genes-central to co-expression and protein-protein interaction-for the biological processes discovered. Notably, a large part of the core genes overlapped with genes previously implicated in nonalcoholic fatty liver disease. Single-nucleus ATAC-seq, combined with data-driven statistical analysis, offers insight into in vivo global gene regulation as a combination of modules and assists in identifying core genes of relevant biological processes.

Self-construal and behavioral motivation systems among patients with depression in Indonesia: A hospital-based study.

Objective: To validate Indonesian versions of two social/cultural psychological scales: the Self-Construal Scale (SCS) that measures independent and interdependent cultural values, and the Behavioral Inhibition (Avoidance) System and Behavioral Approach System (BIS/BAS) that measures motivation focus. We also explored the cultural background for the rising prevalence of depression in Indonesia. Design: Case (hospital)-control (population) study. Setting: Hasanuddin University Hospital (cases) and Makassar city region (controls), Indonesia. Participants: Participants (N = 369) were 165 patients with depression recruited from a university hospital, and 204 healthy controls without a history of mental disorders recruited from locations within a 30-minute walk from the hospital. Outcome measures: Depression was diagnosed by psychiatrists with reference to Indonesian mental disorder guidelines (Pedoman Penggolongan dan Diagnosa Gangguan Jiwa edisi 3). Participants' independent and interdependent cultural values, and neural motivational systems were measured with the SCS and BIS/BAS. Results: Exploratory and confirmatory factor analyses showed that our revised 12-item SCS and the 13-item, three-factor BIS/BAS had a good model fit for the Indonesian population. MANCOVA showed that the SCS Independent subscale and the BAS subscales were significantly associated with depression after adjustment for age, sex, religion, education, and occupation. Conclusion: These findings may guide provision of appropriate treatment for patients based on their social and cultural environment. In addition, this study contributes to understanding underlying reasons for the increasing prevalence of depression in Indonesia, where society is changing from traditional collectivism to global individualism.

Associations between urinary heavy metal concentrations and blood pressure in residents of Asian countries.

BACKGROUND: Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam). METHODS: This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index. RESULTS: The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 µg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them. CONCLUSIONS: Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

Socio-economic-demographic determinants of depression in Indonesia: A hospital-based study.

The association of socio-economic-demographic (SED; e.g., income-related) factors with depression is widely confirmed in the literature. We conducted a hospital-based case-control study of 160 patients with psychiatrist-diagnosed clinical depression. The control group comprised 160 participants recruited from local communities. We used a questionnaire to collect SED data from all participants. We replaced missing values using multiple imputation analyses and further analyzed the pooled data of five imputations. We also recorded the results from the original analysis and each imputation. Univariate analyses showed income was associated with depression. Multiple logistic regression analyses revealed that, among all SED variables, high income (odds ratio = 2.088 [95% confidence interval = 1.178-3.700]; p = 0.012), middle-level (completed junior or senior high school) education (1.688 [1.042-2.734]; p = 0.033) and cohabitating with four or more family members (1.632 [1.025-2.597]; p = 0.039) were significant predictors for the case group. We conclude that cash income is a determinant of depression in hospital outpatients in Indonesia. This study suggests health policy implications toward better hospital access and service for people with depression in middle- or low-income households, and recommends considering high income as correlated with a high risk of depression, owing to socio-cultural changes.

Water Sources Quality in Urban Slum Settlement along the Contaminated River Basin in Indonesia: Application of Quantitative Microbial Risk Assessment.

Fecal contamination in water sources is still found globally, especially in urban slum areas of mid-low income countries. Fecal contamination as an indicator of low levels of hygiene and sanitation practices as well as poor management of drinking water supply might increase the risk of waterborne diseases in developing countries like Indonesia. This study aimed to assess quality of all water sources in one of the urban slum settlements along a contaminated river basin in Indonesia. A cross-sectional survey was conducted during the period of August to October 2015. Water samples were taken with simple random sampling from households in urban slum areas along the Cikapundung river basin in the center of Bandung city, Indonesia. Water samples (n=379) from 199 households and 15 common wells were tested for microbiological contamination, and 61 samples of ground water sources and river were tested for selected heavy metal contamination. Annual risk of infection from all water sources was calculated using the quantitative microbial risk assessment. Tap water distribution was poor in this slum area. Most of the dug wells and half of refill bottled water were contaminated. Estimated highest annual risks of infection due to fecal contamination would be caused by dug well and spring water since majority of the households did not use septic tank and disposed human waste directly to the river. Improvement in point-of-use water treatment and storage is essential to prevent risk of waterborne diseases, and tap water should be more accessible and affordable in urban slum areas. The integrated monitoring system to control the quality of refill bottled water production is one of the many essential issues to be prioritized.

Differences in the responses of three plasma selenium-containing proteins in relation to methylmercury-exposure through consumption of fish/whales.

Putative protective effects of selenium (Se) against methylmercury (MeHg) toxicity have been examined but no conclusion has been reached. We recently reported the lack of serious neurological symptoms in a Japanese fish-eating population with high intakes of MeHg and suggested a potential protective role for Se. Here, relationships between levels of Hg and Se in the blood and plasma samples, with a quantitative evaluation of Se-containing proteins, obtained from this population were examined. While levels of the whole-blood Hg (WB-Hg) and plasma Se (P-Se) showed a positive correlation, stratified analysis revealed that they correlated only in samples with higher (greater than the median) levels of MeHg. A food frequency questionnaire showed that consumption of fish/whales correlated with WB-Hg, but not with P-Se, suggesting that the positive correlation between WB-Hg and P-Se might not be the result of co-intake of these elements from seafood. Speciation of plasma Se revealed the differences in the responses of two plasma selenoproteins, glutathione peroxidase (GPx) and selenoprotein P (SePP), in relation to Hg exposure. In the high-Hg group, SePP showed a positive correlation with WB-Hg, but GPx did not. In the low-Hg group, neither SePP nor GPx showed any correlation with WB-Hg. These observations suggest that the increase in P-Se in the high-Hg group might be associated with an increase in SePP, which may, in turn, suggest an increased demand for one or more selenoproteins in various organs, for which SePP supplies the element.

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal.

BACKGROUND: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. OBJECTIVES: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. METHODS: Adolescents aged 12-16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. RESULTS: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33µg/g creatinine and 196.0±301.1µg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (ß=-0.24, 95% CI -0.42,-0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. CONCLUSIONS: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents.

Double Burden of Malnutrition in Rural West Java: Household-Level Analysis for Father-Child and Mother-Child Pairs and the Association with Dietary Intake.

Indonesia is facing household-level double burden malnutrition. This study aimed at examining (1) household-level double burden for the mother-child and father-child pairs; (2) risk of adiposity of double burden households; and (3) associated dietary factors. Subjects were 5th and 6th grade elementary school children (n = 242), their mothers (n = 242), and their fathers (n = 225) in five communities (1 = urban, 4 = rural) in the Bandung District. Questionnaires on socioeconomic factors, blood hemoglobin measurements, and anthropometric measurements were administered. For adults, body fat percentage (BF%) was estimated by bioelectrical impedance (BF%-BI) and by converting skinfold thickness (ST) data using Durnin and Womersley's (1974) formula (BF%-ST). Food frequency questionnaires were also completed. Double burden was defined as coexistence of maternal or paternal overweight (Body mass index (BMI) ≥ 23) and child stunting (height-for-age z-score <-2) within households. Maternal-child double burden occurred in 30.6% of total households, whereas paternal-child double burden was only in 8.4%. Mothers from double burden households showed high adiposity; 87.3% with BF%-BI and 66.2% with BF%-ST had BF% >35%, and 60.6% had waists >80 cm. The major dietary patterns identified were "Modern" and "High-animal products". After controlling for confounding factors, children in the highest quartile of the "High-animal products" dietary pattern had a lower risk of maternal-child double burden (Adjusted OR: 0.46, 95% CI: 0.21-1.04) than those in the lowest quartile. Given that the "High-animal products" dietary pattern was associated with the decreased risk of maternal-child double burden through a strong negative correlation with child stunting, improving child stunting through adequate intake of animal products is critical to solve the problem of maternal-child double burden in Indonesia.

Delta-aminolevulinic acid dehydratase (ALAD) polymorphism in lead exposed Bangladeshi children and its effect on urinary aminolevulinic acid (ALA).

BACKGROUND AND OBJECTIVE: Lead has long been recognized as a harmful environmental pollutant. People in developing countries like Bangladesh still have a higher risk of lead exposure. Previous research has suggested that the delta-aminolevulinic acid dehydratase (ALAD) genotype can modify lead toxicity and individual susceptibility. As children are more susceptible to lead-induced toxicity, this study investigated whether the ALAD genotype influenced urinary excretion of delta-aminolevulinic acid (U-ALA) among children exposed to environmental lead in Bangladesh. METHODS: Subjects were elementary schoolchildren from a semi-urban industrialized area in Bangladesh. A total of 222 children were studied. Blood and urine were collected to determine ALAD genotypes, blood lead levels and urinary aminolevulinic acid (U-ALA). RESULTS: The mean BPb level was 9.7 µg/dl for the study children. BPb was significantly positively correlated with hemoglobin (p<0.01). In total, allele frequency for ALAD 1 and 2 was 0.83 and 0.17 respectively. The mean U-ALA concentration was lower in ALAD1-2/2-2 carriers than ALAD1-1 carriers for boys (p=0.001). But for girls, U-ALA did not differ significantly by genotype (p=0.26). When U-ALA was compared by genotype at the same exposure level in a multiple linear regression analysis, boys who were ALAD1-2/2-2 carriers still had a lower level of U-ALA compared to ALAD1-1 carriers. CONCLUSION: This study provides information about the influence of ALAD polymorphism and its association with U-ALA in Bangladeshi children. Our results indicate that the ALAD1-2/2-2 genotype may have a protective effect in terms of U-ALA for environmentally lead exposed boys.

Arsenic exposure increases maternal but not cord serum IgG in Bangladesh.

BACKGROUND: Thousands of pregnant women are exposed to arsenic (As), which has been shown to lead to a higher risk of maternal and infant morbidity. We hypothesized that As-induced modifications to the humoral immune system may be partly responsible, and examined the relationship between As and immunoglobulin G (IgG). METHODS: Pregnant women were recruited in As-contaminated rural areas in Bangladesh. Blood and urine samples, and questionnaire data were collected. We analyzed data from 202 pregnant women and a subset of 121 mother-infant pairs. Urinary As was measured on inductively coupled plasma-mass spectrometry and adjusted with specific gravity (U-AsSG ). Maternal (IgGmat ) and cord (IgGcord ) serum total IgG were measured using immunoturbidity assay. RESULTS: The geometric mean U-AsSG (n = 202) was 69 µg/L (range, 3.1-1356 µg/L). Urinary-AsSG was significantly associated with IgGmat (n = 202; (r = 0.24; 95% confidence interval [CI]: 0.10-0.36; P < 0.001) and remained so after the inclusion of maternal-associated variables in a multiple-regression model (ß = 1.26; 95%CI: 0.47-2.05; P < 0.01). U-AsSG , however, was not significantly associated with IgGcord (n = 121), while IgGmat and IgGcord were also not associated with each other. CONCLUSIONS: Maternal As exposure was positively associated with IgGmat but not IgGcord . Elevated IgGmat may have implications as regards maternal morbidity and the placental transfer of specific IgGs. Further studies are required to better understand how As may affect maternal and child health by modifying the humoral immune system.

Methylmercury exposure and neurological outcomes in Taiji residents accustomed to consuming whale meat.

Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to the central nervous system. In Japan, industrial emission of MeHg has resulted in MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans are exposed to MeHg derived from natural sources, primarily fish and fish predators. Therefore, MeHg continues to be an environmental risk to human health, particularly in susceptible populations that frequently consume substantial amounts of fish or fish predators such as whale. This study aimed to investigate the health effects of MeHg exposure in adults. The subjects were 194 residents (117 males, 77 females; age 20-85 years) who resided in the coastal town of Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for mercury content and performed detailed neurological examinations and dietary surveys. Audiometry, magnetic resonance imaging, and electromyography were performed to diagnose neurological defects. Whole blood mercury and selenium (Se) levels were measured in 23 subjects. The geometric mean of the hair mercury levels was 14.9 µg/g. Twelve subjects revealed hair mercury levels >50 µg/g (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale meat intake. These results suggested that residents in Taiji were highly exposed to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression analysis demonstrated no significant correlations between hair mercury levels and neurological outcomes, whereas some of the findings significantly correlated with age. A significantly positive correlation between whole blood mercury and Se levels was observed and the whole blood mercury/Se molar ratios of all subjects were <1. These findings suggested that sufficient Se intake might be one of causes of the absence of adverse effects of MeHg exposure in this study.

Home environment and prenatal exposure to lead, arsenic and zinc on the neurodevelopment of six-month-old infants living in Chitwan Valley, Nepal.

BACKGROUND: We have previously reported the inverse associations between in utero levels of lead (Pb), arsenic (As) (i.e., toxic elements), and neurodevelopmental indicators (i.e., motor and state regulation cluster score) measured by the Brazelton Neonatal Behavioral Assessment Scale, third edition (NBAS III) in this cohort at birth. Using additional follow-up, this study investigated the effects of cord blood levels of Pb, As, and zinc (Zn) (an essential element) and the postnatal environment on the neurodevelopment of 6-month-old infants in Chitwan Valley, Nepal. METHODS: In total, 100 mother-infant pairs were recruited from Chitwan District, Nepal. Pb, As, and Zn concentrations in cord blood were measured. Postnatal raising environment (i.e., HOME score or home environment hereafter) was evaluated using the Home Observation for Measurement of Environment (HOME) scale. Neurodevelopment of infants at 6 months (n=94) was assessed according to the Bayley Scale of Infant Development, second edition (BSID II). Multivariable regression adjusting for covariates was performed to determine the associations of in utero levels of toxic and essential elements and the home environment with neurodevelopment scores. RESULTS: Cord blood levels of Pb, As, and Zn were not associated with any BSID II cluster scores in 6-month-old infants. The total HOME score was positively associated with the Psychomotor Development Index (PDI) score (coefficient=0.59, 95% confidence interval [CI]=0.04 to 1.13). CONCLUSION: In this cohort, detrimental effects of in utero Pb and As on neurodevelopmental indicators observed at birth did not persist at 6 months of age, while it showed an association between the neurodevelopment and home environment.

Cord blood levels of toxic and essential trace elements and their determinants in the Terai region of Nepal: a birth cohort study.

The purpose of this study is to evaluate the cord blood level of toxic and trace elements and to identify their determinants in Terai, Nepal. One hundred pregnant women were recruited from one hospital in Chitwan, Nepal in 2008. The cord blood levels of toxic [lead (Pb), arsenic (As), and cadmium (Cd)], essential trace elements [zinc (Zn), selenium (Se), and copper (Cu)], demographic, socioeconomic, and behavioral variables were measured. The mean values of Pb, As, Cd, Zn, Se, and Cu in cord blood level were found as 31.7, 1.46, 0.39, 2,286, 175, and 667 µg/L, respectively. In the multivariate regression model, cord blood As levels from less educated mothers were higher than those from educated mothers (coefficient = -0.01, 95% confidence interval [CI] = -0.02-0.00). The maternal age was positively associated with the cord blood Cd level (coefficient = 0.02, 95% CI = 0.01-0.03), while it was negatively associated with the cord blood As level (coefficient = -0.01, 95% CI = -0.03--0.01). Cord blood levels of Pb, Zn, Se, and Cu were not associated with maternal age, socioeconomic status, living environment, and smoking status. As and Cd levels were relatively lower than those reported in previous studies in Asia, while the levels of Pb and the trace elements were similar. Less educated mothers are more likely to become a higher in utero As source to their fetus, and fetuses of older mothers were more likely to have higher in utero Cd exposure in Terai, Nepal.

Communicable and non-communicable diseases in the Solomon Islands villages during recovery from a massive earthquake in April 2007.

AIM: The major causes of mortality and morbidity have changed from infectious diseases and malnutrition conditions to non-communicable diseases (NCDs) in Melanesian societies. However, a massive earthquake and its related changes might have disturbed the patterns. This study aimed to explore which health problems were likely to be prevalent during the recovery process from the 2 April 2007 earthquake in the Solomon Islands. METHODS: Participants were recruited in Titiana, a severely damaged village located near a town; Tapurai, a severely damaged remote village; Mondo, a severely damaged, medium urban village; and Olive, a control village. Health indicators measured were classified into communicable and nutritional conditions (malaria, malnutrition, infection status and child growth) and NCDs (overweight/obesity, hypertension and diabetes). RESULTS: Titiana residents were more at risk of infectious conditions (C-reactive protein greater than and equal to 1 mg/dL) and obesity (BMI greater than and equal to 30 kg/m²). Tapurai and Mondo residents were at risks of infectious conditions and becoming overweight (BMI greater than and equal to 25 kg/m²), respectively. Titiana and Mondo residents complained about insufficient subsistence production. CONCLUSION: The urban communities were found to be at risks of both communicable and NCDs. Controlling the urbanisation as well as providing continuous support against infectious conditions during the recovery process would be beneficial.