ABSTRACT
Air pollution exposure may increase the demand for emergency healthcare services, particularly in South-East Asia, where the burden of air-pollution-related health impacts is high. This article aims to investigate the association between air quality and emergency hospital admissions in Singapore. Quasi-Poisson regression was applied with a distributed lag non-linear model (DLNM) to assess the short-term associations between air quality variations and all-cause, emergency admissions from a major hospital in Singapore, between 2009 and 2017. Higher concentrations of SO2, PM2.5, PM10, NO2, and CO were positively associated with an increased risk of (i) all-cause, (ii) cardiovascular-related, and (iii) respiratory-related emergency admissions over 7 days. O3 concentration increases were associated with a non-linear decrease in emergency admissions. Females experienced a higher risk of emergency admissions associated with PM2.5, PM10, and CO exposure, and a lower risk of admissions with NO2 exposure, compared to males. The older adults (≥65 years) experienced a higher risk of emergency admissions associated with SO2 and O3 exposure compared to the non-elderly group. We found significant positive associations between respiratory disease- and cardiovascular disease-related emergency hospital admissions and ambient SO2, PM2.5, PM10, NO2, and CO concentrations. Age and gender were identified as effect modifiers of all-cause admissions.
Subject(s)
Air Pollutants , Air Pollution , Male , Female , Humans , Aged , Middle Aged , Air Pollutants/analysis , Nitrogen Dioxide/analysis , Singapore/epidemiology , Air Pollution/adverse effects , Air Pollution/analysis , Particulate Matter/analysis , Hospitals , ChinaABSTRACT
Development of primordial germ cells (PGCs) is required for reproduction. During PGC development in mammals, major epigenetic remodeling occurs, which is hypothesized to establish an epigenetic landscape for sex-specific germ cell differentiation and gametogenesis. In order to address the role of embryonic ectoderm development (EED) and histone 3 lysine 27 trimethylation (H3K27me3) in this process, we created an EED conditional knockout mouse and show that EED is essential for regulating the timing of sex-specific PGC differentiation in both ovaries and testes, as well as X chromosome dosage decompensation in testes. Integrating chromatin and whole genome bisulfite sequencing of epiblast and PGCs, we identified a poised repressive signature of H3K27me3/DNA methylation that we propose is established in the epiblast where EED and DNMT1 interact. Thus, EED joins DNMT1 in regulating the timing of sex-specific PGC differentiation during the critical window when the gonadal niche cells specialize into an ovary or testis.
Subject(s)
Germ Cells , Histones , Polycomb Repressive Complex 2 , Animals , Cell Differentiation/genetics , DNA Methylation , Ectoderm/embryology , Female , Germ Cells/metabolism , Gonads/metabolism , Histones/genetics , Histones/metabolism , Male , Mice , Polycomb Repressive Complex 2/genetics , Polycomb Repressive Complex 2/metabolismABSTRACT
BACKGROUND: This study aimed to determine to what extent an aging population and shift to chronic illness has contributed to emergency admissions at a tertiary care hospital over ten years. METHODS: This was a retrospective observational study performed using a database of all emergency admissions from the Emergency Department (ED) at a single tertiary hospital in Singapore during a ten-year period (January 1st, 2008 to December 31st, 2017). Emergency admissions were defined as ED visits with inpatient admission as the disposition. This study analyzed the trends of demographics, pre-existing comorbidities, chronic conditions or ambulatory care sensitive conditions (ACSC) of all patients who underwent emergency admissions in Singapore General Hospital. RESULTS: A total of 446,484 emergency records were included. For elderly patients, the proportions of them had pre-existing multimorbidity at the time of undergoing emergency admissions were found to be lower at the end the 10-year study period relative to the beginning of the study period. The proportions of emergency admissions whose ED primary diagnoses were categorized as chronic conditions and certain chronic ACSC including chronic obstructive pulmonary disease, congestive heart failure, diabetes complications, and epilepsy also decreased for elderly patients over the 10-year study period. CONCLUSIONS: In Singapore, despite a rapidly aging population, there have been surprisingly lower proportions of chronic conditions, pre-existing comorbidities, and chronic ACSC among the elderly emergency admissions. This is possibly consistent with an overall improved management of the chronic conditions among the elderly population. Future studies should include similar studies at the national level and comparison with other healthcare settings in different countries.
Subject(s)
Ambulatory Care Sensitive Conditions , Pulmonary Disease, Chronic Obstructive , Adult , Aged , Emergency Service, Hospital , Hospitalization , Humans , Tertiary Care CentersABSTRACT
Remodeling DNA methylation in mammalian genomes can be global, as seen in preimplantation embryos and primordial germ cells (PGCs), or locus specific, which can regulate neighboring gene expression. In PGCs, global and locus-specific DNA demethylation occur in sequential stages, with an initial global decrease in methylated cytosines (stage I) followed by a Tet methylcytosine dioxygenase (Tet)-dependent decrease in methylated cytosines that act at imprinting control regions (ICRs) and meiotic genes (stage II). The purpose of the two-stage mechanism is unclear. Here we show that Dnmt1 preserves DNA methylation through stage I at ICRs and meiotic gene promoters and is required for the pericentromeric enrichment of 5hmC. We discovered that the functional consequence of abrogating two-stage DNA demethylation in PGCs was precocious germline differentiation leading to hypogonadism and infertility. Therefore, bypassing stage-specific DNA demethylation has significant consequences for progenitor germ cell differentiation and the ability to transmit DNA from parent to offspring.