Circadian disruption, clock genes, and metabolic health.

A growing body of research has identified circadian-rhythm disruption as a risk factor for metabolic health. However, the underlying biological basis remains complex, and complete molecular mechanisms are unknown. There is emerging evidence from animal and human research to suggest that the expression of core circadian genes, such as circadian locomotor output cycles kaput gene (CLOCK), brain and muscle ARNT-Like 1 gene (BMAL1), period (PER), and cyptochrome (CRY), and the consequent expression of hundreds of circadian output genes are integral to the regulation of cellular metabolism. These circadian mechanisms represent potential pathophysiological pathways linking circadian disruption to adverse metabolic health outcomes, including obesity, metabolic syndrome, and type 2 diabetes. Here, we aim to summarize select evidence from in vivo animal models and compare these results with epidemiologic research findings to advance understanding of existing foundational evidence and potential mechanistic links between circadian disruption and altered clock gene expression contributions to metabolic health-related pathologies. Findings have important implications for the treatment, prevention, and control of metabolic pathologies underlying leading causes of death and disability, including diabetes, cardiovascular disease, and cancer.

Geographic Isolation and Vulnerability Across Peru's Ecological Regions: The Influence of Regional Contexts of Extraction.

Geographically isolated places are often sites of exported environmental risks, intense resource extraction, exploitation and marginalization, and social policy neglect. These conditions create unique challenges related to vulnerability and adaptation that have direct disaster management implications. Our research investigates the relationship between geographic isolation and flood-related social vulnerability across Peru's ecological regions. Ecoregions have different relationships with colonialism and capitalism that shape vulnerability, and we hypothesize that the relationship between vulnerability and geographic isolation varies across ecoregions. Using mapping techniques and spatial regression analysis, we find that relationships between vulnerability and geographic isolation vary regionally, with differences that suggest alignment with regional contexts of extraction. We find notable differences in vulnerability related to public health infrastructure and access to services and between ecoregions with sharply contrasting histories of natural resource extraction and investment and disinvestment.

Wisconsin microbiome study, a cross-sectional investigation of dietary fibre, microbiome composition and antibiotic-resistant organisms: rationale and methods.

INTRODUCTION: Prevention of multidrug-resistant organism (MDRO) infections, such as those caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, fluoroquinolone-resistant Gram-negative bacteria and Clostridium difficile is crucial. Evidence suggests that dietary fibre increases gut microbial diversity, which may help prevent colonisation and subsequent infection by MDROs. The aim of the Winning the War on Antibiotic Resistance (WARRIOR) project is to examine associations of dietary fibre consumption with the composition of the gut microbiota and gut colonisation by MDROs. The secondary purpose of the study is to create a biorepository of multiple body site specimens for future microbiota research. METHODS AND ANALYSIS: The WARRIOR project collects biological specimens, including nasal, oral and skin swabs and saliva and stool samples, along with extensive data on diet and MDRO risk factors, as an ancillary study of the Survey of the Health of Wisconsin (SHOW). The SHOW is a population-based health survey collecting data on several different health determinants and outcomes, as well as objective body measurements and biological specimens. WARRIOR participants include 600 randomly selected Wisconsin residents age 18 and over. Specimens are screened for MDRO colonisation and DNA is extracted for 16S ribosomal RNA-based microbiota sequencing. Data will be analysed to assess the relationship between dietary fibre, the gut microbiota composition and gut MDRO colonisation. ETHICS AND DISSEMINATION: The WARRIOR project is approved by the University of Wisconsin Institutional Review Board. The main results of this study will be published in a peer-reviewed scientific journal.

Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures.

BACKGROUND: Obesity has been shown to alter response to air pollution and smoking but underlying biological mechanisms are largely unknown and few studies have explored mechanisms by which obesity increases human sensitivity to environmental exposures. OBJECTIVE: Overall study goals were to investigate whole blood gene expression in smokers and non-smokers to examine associations between cigarette smoke and changes in gene expression by obesity status and test for effect modification. METHODS: Relative fold-change in mRNA expression levels of 84 genes were analyzed using a Toxicity and Stress PCR array among 50 21-54 year old adults. Data on smoking status was confirmed using urinary cotinine levels. Adjusted models included age, gender, white blood cell count and body-mass index. RESULTS: Models comparing gene expression of smokers vs. non-smokers identified six differentially expressed genes associated with smoking after adjustments for covariates. Obesity was associated with 29 genes differentially expressed compared to non-obese. We also identified 9 genes with significant smoking/obesity interactions influencing mRNA levels in adjusted models comparing expression between smokers vs non-smokers for four DNA damage related genes (GADD45A, DDB2, RAD51 and P53), two oxidative stress genes (FTH1, TXN), two hypoxia response genes (BN1P3lL, ARNT), and one gene associated with unfolded protein response (ATF6B). CONCLUSIONS: Findings suggest that obesity alters human sensitivity to smoke exposures through several biological pathways by modifying gene expression. Additional studies are needed to fully understand the clinical impact of these effects, but risk assessments should consider underlying phenotypes, such as obesity, that may modulate sensitivity of vulnerable populations to environmental exposures.

Heavy metal exposure and nasal Staphylococcus aureus colonization: analysis of the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Heavy metals including lead and cadmium can disrupt the immune system and the human microbiota. and are increasingly of concern with respect to the propogation of antibiotic-resistence. Infection by methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of global morbidity and mortality. Heavy metal exposure may be associated with increased MRSA colonization and infection, and a decrease in methicillin-susceptible Staphylococcus aureus (MSSA) through co-selection mechanisms and natural selection of antibiotic resistance in the presence of heavy metals. This study examines the association between blood lead (Pb) and cadmium (Cd) level, and MRSA and MSSA nasal colonization. METHODS: All data used for this analysis came from the 2001-2004 National Health and Nutrition Examination Survey (NHANES). The analytical sample consisted of 18,626 participants aged 1 year and older. Multivariate logistic regression, including adjustment for demographic and dietary factors, was used to analyze the association between blood Pb and Cd, and nasal colonization by MRSA and MSSA. RESULTS: Prevalence of MRSA and MSSA carriage were 1.2%, and 29.3% respectively. MRSA was highest in women, individuals age 70 and older, who self-identified as black, had only a high school diploma, lived below 200% of the Federal Poverty Level, and had a history of smoking. While not significantly different from those colonized with MSSA, geometric mean blood Pb (1.74 µg/dL) and blood Cd (0.31 µg/L) were highest in those colonized with MRSA. Associations with MRSA colonization appeared to increase in a dose-dependent manner with increasing quartile of blood Pb level. Blood Cd level in the fourth quartile was also significantly associated with lower odds of MRSA colonization. Both metals were associated with lower odds of MSSA colonization. CONCLUSIONS: Both MRSA and MSSA results suggest that general population levels of blood Pb but not Cd are associated with differences in nasal carriage of S. aureus. While further research is needed, reduction in heavy metal exposures such as lead, concurrently with maintaining a healthy microbiota may be two modifiable options to consider in the fight against antibiotic-resistance.

Allergic disease associations with regional and localized estimates of air pollution.

BACKGROUND: Exposure to multiple types of air pollution may contribute to and exacerbate allergic diseases including asthma and wheezing. However, few studies have examined chronic air pollution exposure and allergic disease outcomes among an adult population. Associations between potential estimates of annual average fine particulate matter (PM2.5), traffic related air pollution, and industrial source air emissions and three allergic disease outcomes (asthma, allergies and wheezing) were examined in a state-wide general population of adults. METHODS: The study includes a representative sample of 3381 adult Wisconsin residents who participated in the 2008-2013 Survey of the Health of Wisconsin (SHOW) program. Participant data were geographically linked to The United States Environmental Protection Agency (USEPA) Baysian space-time downscaler air pollution model for PM2.5, the United States Census roadway, and USEPA's Toxic Release Inventory data. Self-report and lung function (FEV1) estimates were used to define prevalence of asthma, allergies and wheezing symptoms. RESULTS: Annual mean exposure to fine particulate matter (PM2.5) was between 6.59 and 15.14µg/m3. An increase of 5µg/m3 in the annual mean PM2.5 resulted in a 3.58 (2.36, 5.43) increase in the adjusted odds (95% CI) of having asthma. Exposure to vehicle traffic increased the odds of both current allergies [OR (95% CI)=1.35 (1.07, 1.35)] and current asthma [OR (95% CI)=1.51 (1.14, 2.00)]. Living within 300m of an Interstate roadway was associated with a 3-fold increase in the odds of asthma. Those living within 800m of an industrial site were 47% more likely to have asthma. No significant associations were seen with wheezing. CONCLUSIONS: Within this population exposed to overall annual average levels of estimated low level chronic exposure to fine particulate matter (PM2.5) at or near 12µg/m3, the USEPA standard for air quality, significant association between both modeled PM2.5 exposure and proximity to roadways with asthma and allergies but not wheezing were found. Industrial source emissions were not associated with any allergic disease outcomes.