Multi-tissue DNA methylation age: Molecular relationships and perspectives for advancing biomarker utility

The multi-tissue DNA methylation estimator of chronological age (DNAm-age) has been associated with a wide range of exposures and health outcomes. Still, it is unclear how DNAm-age can have such broad relationships and how it can be best utilized as a biomarker. Understanding DNAm-age’s molecular relationships is a promising approach to address this critical knowledge gap. In this review, we discuss the existing literature regarding DNAm-age’s molecular relationships in six major categories: animal model systems, cancer processes, cellular aging processes, immune system processes, metabolic processes, and nucleic acid processes. We also present perspectives regarding the future of DNAm-age research, including the need to translate a greater number of ongoing research efforts to experimental and animal model systems.     

A national survey of caregivers’ perspective of early symptoms of dementia among adults with an intellectual disability based on the DSQIID scale

As life expectancy increases for persons with an intellectual disability, concerns have been raised that there will be an increased demand for health or social services, particularly to address the challenges posed by the problems of dementia. To plan services for people with an intellectual disability who might experience the consequences of aging, an important first step is to obtain epidemiological data on the prevalence of dementia in this vulnerable population. This study aimed to investigate the dementia prevalence rate and its associated demographical factors in adults with an intellectual disability in Taiwan. A national survey was conducted to recruit 460 community residents of at least 45 years of age with an intellectual disability. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) was administered to caregivers to determine the symptoms of dementia in adults with an intellectual disability. The results indicated that 16.5% of the adults with an intellectual disability might have dementia conditions (DSQIID score ≧ 20). After controlling for other factors in a multiple logistic regression analysis, the older adults with intellectual disability (≧55 vs. 45–54, OR = 2.594, 95% CI = 1.438–4.679) and those individuals with a comorbid diagnosis of mental illness or neurological disease (with vs. without, OR = 2.826, 95% CI = 1.593–5.012) had a higher risk of dementia than their counterparts. This study suggests that further longitudinal studies are needed to examine the specific aspects of the functions of living and morbidity that might be affected by aging and concomitant conditions in adults with an intellectual disability.     

Re-Examination of the Genotoxic Activity of Water Taken From the Songhua River in P. R. China

The Songhua River, in northeast China, has heavy organic contamination due to domestic sewage and industrial wastewater. Thus, it is important to further determine its genotoxic activity, which is a potential hazard for human health. Short-term genotoxic bioassays using Salmonella, the cytokinesis-block micronucleus cytome assay, and mouse liver cell comet assay were employed to further examine the genotoxic activity of diethyl ether extracts of water samples taken from the Songhua River. Ames test results showed that there were still frame-shift mutagens, both direct and indirect, in water samples at doses of 5.0 or 7.0 L water equivalent/plate. The mutagenicity seems to be less when compared with the results from 2002 to 2003. A dose–response relationship was also obtained between DNA damage in mouse liver cells by comet assay and micronuclei formation by CBMN assay. These results indicate that the water samples showed genotoxic activity with a mutagenic potency. 88 and 104 compounds, respectively, were identified in summer and winter water sample extracts by gas chromatography–mass spectrometry analysis. Four priority pollutants listed by the United States Environmental Protection Agency and six priority pollutants listed by the Chinese Environment Protection Agency were found in summer or winter water samples, respectively. The results indicate that the diethyl ether extracts of surface water samples taken from the Songhua River still show genotoxic activity (≥3.0 L water). The risks of potential carcinogenicity for human health in the Songhua River should be studied further.     

Genetic predictors of inflammation in the risk of occupational asthma in young apprentices

BackgroundThe influence of genetic predictors of inflammation and atopy on occupational asthma in apprentices is not known.ObjectivesTo assess the influence of genetic polymorphisms of IL4RA, IL13, TNFA, IL1A, and IL5 on the decline of lung function and bronchial hyperresponsiveness in a prospective follow-up study of baker/pastry maker and hairdresser apprentices.MethodsA total of 351 apprentices were included in the study. We performed skin testing, spirometry, fractional exhaled nitric oxide measurement, and methacholine hyperreactivity testing at the initial visit and during and at the end of the 18-month training period. Gene variants of IL4RA, IL13, TNFA, IL1A, and IL5 were determined in DNA from nasal lavage.ResultsIL13 R130Q/IL4RA S478P or IL13 R130Q//IL4RA Q551R were significant predictors of the decrease of forced expiratory volume and forced vital capacity (P ≤ .006). Genotype GG of TNFAG308A was associated with bronchial hyperresponsiveness in the whole population and in nonatopic individuals (90.63% vs 9.38%; odds ratio, 3.78; 95% confidence interval, 1.10-12.83). TNFA GA and IL5 CC and TNFA GA and IL1A CC were 2 epistatic predictors of exhaled nitrogen monoxide decrease during follow-up (P = .02 and P = .004, respectively). The association with TNFA GA and IL1A CC was the most significant in nonatopic bakers (P < .001).ConclusionWe evidenced a predicting influence of IL13/IL4RA and TNFA in the early exposure to allergens and irritants that precedes occupational asthma. The significance of the associations in the absence of atopy suggests an influence of the genetics predictors related to inflammatory pathways.     

Opioids,stimulants, and depressant drugs in fifteen Mexican Cities: A wastewater-based epidemiological study

BackgroundMonitoring drug use in México is a challenge due to emerging drugs and rapid changes in consumption patterns. The temporal and geographical patterns of cocaine, methamphetamine, amphetamine, MDMA, cannabis, heroin, ketamine, and fentanyl were examined in Mexican cities using wastewater-based epidemiology (WBE).Methods105 daily composite wastewater samples were collected from sewage treatment plants in fifteen Mexican cities. We quantified drug residues using liquid chromatography–high-resolution mass spectrometry, and estimated drug use by back-calculation of drug loads.ResultsWe identified ten drug target residues in at least one sample across cities. Drugs with the highest median levels were cannabis, methamphetamine, and cocaine. The median range of cannabis for one week was between 147 and 20,364 mg/day/1000inhab across cities, whereas methamphetamine ranged between 5 and 3,628 mg/day/1000inhab. Cocaine was found in levels between 2 and 370 mg/day/1000inhab. The highest levels of methamphetamine and amphetamine were observed in the US border cities of Tijuana and San Luis Río Colorado. The presence of heroin, MDMA, ketamine, and fentanyl was stronger during weekends, while cannabis, cocaine, and amphetamine were found throughout the week.ConclusionThis study provides the first report of fentanyl, norfentanyl, and ketamine in wastewater in Mexico. The results indicate an increased presence of drugs on known drug traffic routes, demonstrating that WBE can help identify areas of high drug use and assist governments in developing policies to reduce drug use and harm in the communities.     

Rate of eating in early life is positively associated with current and later body mass index among young Japanese children: the Osaka Maternal and Child Health Study

The possible effect of eating rate on promoting obesity has attracted considerable attention among various age groups, but little is known about these associations in an early stage of life. We investigated the hypothesis that eating rate in early childhood influences current and later body mass index (BMI) among young Japanese children. The study participants were 492 Japanese mother-child pairs from a prospective birth cohort study. Information on rate of eating (slow, medium, or fast), macronutrient intake (protein, fat, and carbohydrate), and dietary fiber intake were collected from the mothers using a diet history questionnaire when the children were aged 29 to 39 months. Height and weight as measured at 30 and 42 months of age were used to calculate BMI at each age. Multiple linear regression analyses were performed to examine the relationships between eating rate in early childhood and BMI at 30 and 42 months. There were strong positive associations between eating rate and BMI at 30 and 42 months of age that were robust to adjustment for confounders including maternal BMI, socioeconomic status, health behaviors, and child's nutrient intake. In comparison with children in the “slow” rate of eating group, the size of the difference in BMI (95% confidence interval) at 42 months of age was 0.49 (0.17-0.80) and 0.67 (0.24-1.10) kg/m² greater among children in the “medium” and “fast” groups, respectively. In conclusion, a higher rate of eating in early childhood was positively associated with not only current BMI but also BMI measured 1 year later in young Japanese children.