Ambient air pollution and hospitalization for type 2 diabetes in China: A nationwide, individual-level case-crossover study.

Scarce evidence is available on the short-term association between air pollution and type 2 diabetes (T2D). We aimed to evaluate the associations between short-term exposure to six criteria air pollutants and hospitalization for T2D based on a national registry. We conducted an individual-level, time-stratified case-crossover study among inpatients with a primary diagnosis of T2D from 153 hospitals across 20 provincial regions in China (2013-2021). Daily concentrations of fine particulate matter (PM2.5), inhalable particle (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO), and ozone were collected from the nearest monitoring stations. T2D patients were separated into those admission for T2D with and without complications. Distributed lag non-linear models combined with conditional logistic regressions were used to estimate the associations. A total of 88,904 patients were hospitalized for T2D. Short-term exposures to all six air pollutants above except for ozone were significantly associated with the risk of hospitalization for T2D and both subclasses. An interquartile range increase in the concentrations of PM2.5, PM10, NO2, SO2, and CO at lag 0-2 d was associated with higher hospitalization risk of T2D by 1.71% (95%CI: 0.56%, 2.87%), 2.08% (0.88%, 3.29%), 4.85% (3.29%, 6.44%), 2.44% (1.22%, 3.67%) and 2.55% (1.24%, 3.88%), respectively. The associations of T2D hospitalizations were stronger in cold season than in warm season. Air pollutants had more acute and stronger associations with T2D with complications. The exposure-response relationship curves showed no thresholds, and the slopes were larger for T2D with complications. This nationwide individual-level, case-crossover study provides the first comprehensive evidence that short-term exposure to multiple criteria air pollutants may increase the risk of hospitalizations for T2D, especially for T2D with complications.

Common deletions and SNPs are in linkage disequilibrium in the human genome.

Humans show great variation in phenotypic traits such as height, eye color and susceptibility to disease. Genomic DNA sequence differences among individuals are responsible for the inherited components of these complex traits. Reports suggest that intermediate and large-scale DNA copy number and structural variations are prevalent enough to be an important source of genetic variation between individuals. Because association studies to identify genomic loci associated with particular phenotypic traits have focused primarily on genotyping SNPs, it is important to determine whether common structural polymorphisms are in linkage disequilibrium with common SNPs, and thus can be assessed indirectly in SNP-based studies. Here we examine 100 deletion polymorphisms ranging from 70 bp to 7 kb. We show that common deletions and SNPs ascertained with similar criteria have essentially the same distribution of linkage disequilibrium with surrounding SNPs, indicating that these polymorphisms may share evolutionary history and that most deletion polymorphisms are effectively assayed by proxy in SNP-based association studies.

Association between obesity and urinary incontinence in older adults from multiple nationwide longitudinal cohorts.

BACKGROUND: Obesity and urinary incontinence (UI) among older adults, particularly older men, are yet to be fully explored. Utilizing multiple nationwide prospective longitudinal cohorts representative of the US, UK, and European samples, we examined the association of body mass index (BMI) and waist circumference (WC) with UI among both older women and men. METHODS: We derived the data from multiple longitudinal cohorts that surveyed UI. Participants were asked if they had experienced urine leakage within the past 12 months or within the past six months. The measure of obesity was based on BMI and WC. We employed a random-effect logistic model to associate BMI and WC with UI, adjusting for covariates including age, race, education, residence area, marital status, number of children, smoking, drinking, hypertension, diabetes, cancer, stroke, functional ability, and cognitive impairment. We visualized the associations by using restricted cubic spline curves. RESULTS: A total of 200,717 participants with 718,822 observations are included in the baseline analysis. Compared to those without UI, both female and male participants with UI demonstrate a higher BMI and WC. Among females, the fully adjusted models show linear associations between BMI, WC, and UI (Ps < 0.001). However, we observe U-shaped associations of BMI, WC with UI among males. The lowest likelihood of having UI is found among male participants with a BMI between 24 and 35 kg/m2. CONCLUSIONS: Interventions aimed at preventing UI among older adults must take sex into account. Weight loss intervention could be an effective treatment among older females who are overweight and with obesity as well as older males with obesity rather than all older males.

It is not well known if being obese poses a risk of urinary incontinence (UI) in older adults, especially in older men. We aim to address this question by analyzing three nationwide long-term studies conducted in the UK, Europe and USA. We found there was a direct link between increasing body weight and the likelihood of experiencing UI in older females. Whereas, older males who are considered clinically obese were more prone to experiencing UI. This suggests that weight loss intervention can be effective for treating UI in older females carrying extra weight and older males who are considered clinically obese. Our study highlights that sex should be taken into consideration when developing interventions for UI treatment in older adults.

Ambient temperature and ambulatory blood pressure: An hourly-level, longitudinal panel study.

BACKGROUND: Variations of blood pressure (BP) related to air temperature have been reported previously; however, no evidence is available regarding the association of hourly ambient temperature with ambulatory blood pressure. METHODS: We conducted a longitudinal panel study among 1895 patients from an outpatient department who received repeated ambulatory blood pressure monitoring in Urumqi, China between July 2020 and December 2021. We obtained hourly ambient temperature from the nearest monitoring station to the residential address, and measured 4 ambulatory blood pressure indicators. Linear mixed-effect model combined with distributed lag models were applied to investigate the cumulative associations of hourly temperature with BP. RESULTS: A total of 97,466 valid blood pressure measurements were evaluated. We observed almost linear and monotonically decreasing relationships between temperature and blood pressure. The effects occurred in the same hour, attenuated thereafter and became insignificant approximately 36 h. A 10 °C decrease in temperature was significantly associated with increments of 0.84 mmHg in systolic blood pressure, 0.56 mmHg in diastolic blood pressure, 1.38 mmHg in mean arterial pressure, and 0.66 mmHg in pulse pressure over lag 0 to 36 h. Stronger associations were found among patients of female sex, age between 18 and 65 years, overweight or obesity, minority, less education or in the cold season, as well as those without hypertension or with coronary heart disease, or did not take anti-hypertension medication. CONCLUSION: Our study provides robust evidence that hourly ambient temperature is inversely associated with ambulatory blood pressure. It also highlights a linear relationship between decreased ambient temperature and elevated BP, which may have implications for the prevention and management of hypertension in susceptible populations.

Nutrition improvement program for rural compulsory education students and individual health.

We use the county-by-county rollout of the program and employ the difference-in-difference (DID) methodology to identify the effects of the implementation of the nutrition improvement program for rural compulsory education students on adolescent health. The results show that the nutrition improvement program reduces the frequency and probability of illness and improves the students' health status. The heterogeneity analysis indicates that the children in western regions and children left behind have a greater marginal improvement. It finds that the nutrition improvement program for rural compulsory education students improves adolescent health through diversifying nutrition intake to alleviate malnutrition and developmental delay in impoverished areas. The program can promote adolescent health in impoverished areas, which has a role in improving regional health disparities and alleviating the intergenerational entrenchment of poverty.

Short-Term Associations between Size-Fractioned Particles and Cardiopulmonary Function in COPD Patients: A Panel Study in Shanghai, China, during 2014-2021.

It remains unknown which size fractions dominate the adverse cardiopulmonary effects of particulate matter (PM). Therefore, this study aimed to explore the differential associations between size-fractioned particle number concentrations (PNCs) and cardiopulmonary function measures, including the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), and the left ventricular ejection fraction (LVEF). We conducted a panel study among 211 patients with chronic obstructive pulmonary disease (COPD) in Shanghai, China, between January 2014 and December 2021. We applied linear mixed-effect models to determine the associations between cardiopulmonary function measures and PNCs ranging from 0.01 to 10 µm in diameter. Generally, only particles <1 µm showed significant associations, i.e., ultrafine particles (UFPs, <0.1 µm) for FVC and particles ranging from 0.1 to 1 µm for FEV1 and LVEF. An interquartile range (IQR) increment in UFP was associated with decreases of 78.4 mL in FVC. PNC0.1-0.3 and PNC0.3-1 corresponded to the strongest effects on FEV1 (119.5 mL) and LVEF (1.5%) per IQR increment. Particles <1 µm might dominate the cardiopulmonary toxicity of PM, but UFPs might not always have the strongest effect. Tailored regulations towards particles <1 µm should be intensified to reduce PM pollution and protect vulnerable populations.

New developments in high-throughput resequencing and variation detection using high density microarrays.

We developed a high-throughput method for resequencing for single nucleotide polymorphism (SNP) discovery using high-density microarrays. Over the two-year course of this study a number of improvements in sample preparation methods, hybridization assay, array handling, and analysis method were developed and implemented. DNA from 40 unrelated individuals of three different ethnic origins was amplified, labeled, and hybridized to arrays designed with probes representing genomic, coding, and regulatory regions. Protocol improvements including the use of long PCR and semi-automation reduced labeling and fragmentation costs by 33%. Automation improvements include the development of a scanner autoloader for arrays, a faster array wash station, and a linked laboratory tracking and data management system. Validation of a smaller feature size, 20 x 24 microns, allowed the simultaneous screening of 30-kb sense and 30-kb antisense DNA on each microarray, increasing throughput to 1.4 Mb per day per two laboratory personnel. More than 15,000 SNPs were identified in 8.3 Mb of the human genome using high-density resequencing and variation detection arrays (microarrays).

Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates.

Comparative DNA sequence studies between humans and nonhuman primates will be important for understanding the genetic basis of the phenotypic differences between these species. Here we compare approximately 27 Mb of human chromosome 21 with chimpanzee DNA sequences identifying 57 genomic rearrangements (deletions and insertions ranging in size from 0.2 to 8.0 kb) between the two species. These rearrangements are distributed along the entire length of chromosome 21, with approximately 35% found in genomic intervals encoding genes (genic intervals), and have occurred in the genomes of both humans and chimpanzees. Comparison of approximately 9 Mb of human chromosome 21 with orangutan, rhesus macaque, and woolly monkey DNA sequences identified a combined total of 114 genomic rearrangements between humans and nonhuman primates. Analysis of these rearrangements revealed that they are randomly distributed with respect to genic and nongenic intervals and identified one deletion that has likely resulted in the inactivation of a gene (beta1,3-galactosyltransferase) in the woolly monkey. Our data show that genomic rearrangements have occurred frequently during primate genome evolution and significantly contribute to the DNA differences between these species. These DNA rearrangements are commonly found in genic intervals, and thus provide natural starting points for focused investigations of qualitative and quantitative gene expression differences between humans and other primates.

Noncoding sequences conserved in a limited number of mammals in the SIM2 interval are frequently functional.

Cross-species DNA sequence comparison is a fundamental method for identifying biologically important elements, because functional sequences are evolutionarily conserved, wheres nonfunctional sequences drift. A recent genome-wide comparison of human and mouse DNA discovered over 200,000 conserved noncoding sequences with unknown function. Multispecies DNA comparison has been proposed as a method to prioritize these conserved noncoding sequences for functional analysis based on the hypothesis that elements present in many species are more likely to be functional than elements present in limited numbers of species. Here, we perform a comparative analysis of the single-minded 2 (SIM2) gene interval on human chromosome 21 with horse, cow, pig, dog, cat, and mouse DNA. We classify conserved sequences based on the number of mammals in which they are present, and experimentally test sequences in each class for function. As hypothesized, conserved sequences present in many mammals are frequently functional. Additionally, we demonstrate that sequences conserved in a limited number of mammals are also frequently functional. Examination of genomic deletions in chimpanzee and rhesus macaque DNA showed that several putatively functional conserved noncoding human sequences were absent in these primates. These findings suggest that functional conserved noncoding human sequences can be missing in other mammals, even closely related primate species.