Unique Environmental Exposures Research Articles

Associations between Predictors of PTSD and Psychosocial Functioning in Veterans: Results from a Longitudinal Assessment Study

Impairments in psychosocial functioning are common in veterans, especially in those with significant mental health symptoms. Although available treatments are aimed at alleviating these symptoms, impairments in psychosocial functioning do not appear to be fully addressed. To achieve rehabilitation and full societal participation, there is a need to identify longitudinal associations of both symptoms and functional outcomes which can be targeted in treatment. United States veterans (N=491) of the Iraq and Afghanistan wars were recruited as part of a longitudinal assessment study which examined predictors of postdeployment adjustment. Veterans were assessed at four timepoints over the course of a two-year period. A Bayesian multivariate multilevel model was used to estimate the association of predictors of PTSD (depression, alcohol use, suicidal ideation, and sleep) on psychosocial functioning as encompassed by quality of life (Quality of Life Scale (QLS)) and disability (World Health Organization Disability Assessment Schedule (WHODAS)) scores over time. As female veterans have unique environmental exposures and functional demands, interactions between predictors and gender were included in all models. There was significant overlap between predictors of PTSD and predictors of disability across domains and quality of life. Depressive symptoms and social support emerged as the strongest predictors of psychosocial functioning. Additionally, suicidality and alcohol use emerged as predictors of quality of life, but not disability. As expected, increases in PTSD symptoms predicted increased disability and decreased quality of life. The effect of depressive symptoms on quality of life was more pronounced for male veterans, and the effect of PTSD and alcohol use on quality of life was more pronounced for female veterans. Findings highlight various treatment targets which have the potential to improve symptoms of PTSD and functional outcomes. Findings highlight an opportunity to leverage intervention and prevention efforts focused on decreasing depression and increasing social support to improve trauma symptoms and maximize rehabilitation and functional recovery in veterans.

Clinical Features and Biophysical Characteristics of Lips of South Asian Women.

The vermillion lip has unique physical properties and environmental exposures make them prone to dryness and chapping. While lips contribute to facial beauty, perioral aging is highly individual and dependent on ethnicity. Specifically with regard to South Asian population, there is no other literature identified on the biophysical characteristics of the vermillion lip. In this work, characteristics of the vermillion skin in South Asians were examined through various clinical and biophysical characteristics of the lips such as dryness and roughness, fine lip lines, lip texture, hydration, and barrier function. Healthy South Asian females, from age 20-45 were recruited for this study and transepidermal water loss (TEWL), hydration, visual lip tolerance, and visual dryness were measured and graded by the dermatologist-investigator. Lip texture and fine lines significantly increased from the 20s to the 40s. Overall lip health significantly decreased with age. TEWL and dryness increased with age while hydration decreased with age, although not significantly so. This first-of-its kind study on South Asian females establishes that with age there is a decrease in overall lip health and an increase in signs of aging of the lips (fine lines, texture) from the 20s to 40s.

Phenotypic screening models for rapid diagnosis of genetic variants and discovery of personalized therapeutics.

Precision medicine strives for highly individualized treatments for disease under the notion that each individual's unique genetic makeup and environmental exposures imprints upon them not only a disposition to illness, but also an optimal therapeutic approach. In the realm of rare disorders, genetic predisposition is often the predominant mechanism driving disease presentation. For such, mostly, monogenic disorders, a causal gene to phenotype association is likely. As a result, it becomes important to query the patient's genome for the presence of pathogenic variations that are likely to cause the disease. Determining whether a variant is pathogenic or not is critical to these analyses and can be challenging, as many disease-causing variants are novel and, ergo, have no available functional data to help categorize them. This problem is exacerbated by the need for rapid evaluation of pathogenicity, since many genetic diseases present in young children who will experience increased morbidity and mortality without rapid diagnosis and therapeutics. Here, we discuss the utility of animal models, with a focus mainly on C. elegans, as a contrast to tissue culture and in silico approaches, with emphasis on how these systems are used in determining pathogenicity of variants with uncertain significance and then used to screen for novel therapeutics.

The public health exposome and pregnancy-related mortality in the United States: a high-dimensional computational analysis

BackgroundRacial inequities in maternal mortality in the U.S. continue to be stark.MethodsThe 2015–2018, 4-year total population, county-level, pregnancy-related mortality ratio (PRM; deaths per 100,000 live births; National Center for Health Statistics (NCHS), restricted use mortality file) was linked with the Public Health Exposome (PHE). Using data reduction techniques, 1591 variables were extracted from over 62,000 variables for use in this analysis, providing information on the relationships between PRM and the social, health and health care, natural, and built environments. Graph theoretical algorithms and Bayesian analysis were applied to PHE/PRM linked data to identify latent networks.ResultsPHE variables most strongly correlated with total population PRM were years of potential life lost and overall life expectancy. Population-level indicators of PRM were overall poverty, smoking, lack of exercise, heat, and lack of adequate access to food.ConclusionsIn this high-dimensional analysis, overall life expectancy, poverty indicators, and health behaviors were found to be the strongest predictors of pregnancy-related mortality. This provides strong evidence that maternal death is part of a broader constellation of both similar and unique health behaviors, social determinants and environmental exposures as other causes of death.

Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia.

Previous population health studies examining adults with acute myeloid leukemia (AML); however many of these, such as the Cancer Genome Atlas, are derived from databases collected by large urban centers. Due to its unique industry and environmental exposures, we hypothesized the West Virginia Appalachian population may have different mutational trends and clinical outcomes. To address the concern of under-representation of rural minorities in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML in rural Appalachia. Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. A total of 26 patients were identified and whole exome sequencing was performed. Median age was 68 years old. Twenty-one patients had de novo AML (84%). As per European LeukemiaNet (ELN) criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant. The median progression-free survival and overall survival were 16.5months and 26.6months, respectively. We noted an increased tumor mutation burden and a higher frequency of specific known driver mutations when compared to The Cancer Genome Atlas database; we also found novel mutations in MUC3A, MUC5AC, HCAR3, ORT2B, and PABPC. Survival outcomes were slightly lower than national average and BCOR mutation correlated with inferior outcomes. Our findings provide novel insight into detrimental mutations in AML in a rural, underrepresented population. We discovered several novel mutations and higher frequency of some known driver mutations, which will help us identify therapeutic targets to improve patient outcomes.

Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia.

e19022 Background: Many previous population health studies examining adults with acute myeloid leukemia (AML) are derived from national databases within large urban centers. To address the concern of under-representation of rural Appalachian population in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML. As the only stem cell transplantation center in the state, WVU is uniquely situated to capture most of these patients from the state and surrounding area. Due to its unique industry and environmental exposures, we hypothesized that WV may have both different rates of mutations and differing outcomes than the nation as a whole. Methods: We performed whole exome sequencing on 26 patients with newly diagnosed AML from paired bone marrow and buccal samples that were obtained from 2015 to 2017. Whole exome sequencing libraries were prepared using Agilent SureSelect Human Whole Exome technology. The libraries were sequenced on an Illumina HiSeq1500 sequencer using paired end runs. Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. Variables measured included association between biomarker data and progression-free survival (PFS) and overall survival (OS). Results: Median patient age was 68 years and women represented 10 of the patients (37%). Twenty-one patients had de novo AML (84%), 3 patients had preceding MDS (12%), and 1 patient had therapy-related AML (4%). As per ELN criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant with the following donors: 4 MUD (50%), DUCB (37.5%), and 1 haploidentical (12.5%). The median PFS and OS were 16.5 months and 26.6 months, respectively. Tobacco use was the largest known exposure with 7 patients. We noted a similar mutational trend compared to national TCGA data, except for an increased tumor mutation burden and higher frequency of the following mutations as seen in Table. Neither MUC3A or MUC5AC were identified in the TCGA database. Of our five patients with BCOR mutations, two had a co-existing FLT3-ITD mutation, one of which also had a NPM1 mutation. Two patients had secondary AML, while the other 3 had de novo disease. The median OS was 63 days. While not statistically significant, BCOR mutation was trending toward a poor prognostic indicator.Conclusions: Despite our small patient cohort, the findings provide further assessment of predisposing detrimental mutations in AML in the Appalachian region and associated survival outcomes.[Table: see text]

The Heritability of Kidney Function Using an Older Australian Twin Population

IntroductionTwin studies are unique population models which estimate observed rather than inferred genetic components of complex traits. Nonmonogenic chronic kidney disease (CKD) is a complex disease process with strong genetic and environmental influences, amenable to twin studies. We aimed to assess the heritability of CKD using twin analysis and modeling within Older Australian Twin Study (OATS) data.MethodsOATS had 109 dizygotic (DZ) and 126 monozygotic (MZ) twin pairs with paired serum creatinine levels. Heritability of kidney function as estimated glomerular filtration rate (eGFR CKD Epidemiology Collaboration [CKD-EPI]) was modeled using the ACE model to estimate additive heritability (A), common (C), and unique (E) environmental factors. Intratwin pair analysis using mixed effects logistic regression allowed analysis of variation in eGFR from established CKD risk factors.ResultsThe median age was 69.71 (interquartile range 78.4–83.0) years, with 65% female, and a mean CKD-EPI of 82.8 ml/min (SD 6.7). The unadjusted ACE model determined kidney function to be 33% genetically determined (A), 18% shared genetic-environmental (C), and 49% because of unique environment (E). This remained unchanged when adjusted for age, hypertension, and sex. Hypertension was associated with eGFR; however, intertwin variance in hypertension did not explain variance in eGFR. Two or more hypertension medications were associated with decreased eGFR (P = 0.009).ConclusionThis study estimates observed heritability at 33%, notably higher than inferred heritability in genome-wide association study (GWAS) (7.1%–18%). Epigenetics and other genomic phenomena may explain this heritability gap. Difference in antihypertension medications explains part of unique environmental exposures, though discordance in hypertension and diabetes does not.

Dietary habits and the gut microbiota in military Veterans: results from the United States-Veteran Microbiome Project (US-VMP).

Dietary patterns influence gut microbiota composition. To date, there has not been an assessment of diet and gut microbiota in Veterans, who have a history of unique environmental exposures, including military deployment, that may influence associations between diet and gut microbiota. Our aim was to characterise Veteran habitual dietary intake and quality, and to evaluate correlations between diet and gut microbiota. We administered Food Frequency Questionnaires (FFQs) and collected stool samples from 330 Veterans. FFQ data were used to generate Healthy Eating Indices (HEI) of dietary quality. Exploratory factor analysis was used to identify two dietary patterns we defined as "Western" and "Prudent." Stool samples underwent 16S rRNA gene sequencing, and the resulting data were used to evaluate associations with dietary variables/indices. Analyses included linear regression of α-diversity, constrained analysis of principal coordinates of β-diversity, and multivariate association with linear models and Analysis of Composition of Microbiomes analyses of dietary factors and phylum- and genus-level taxa. There were no significant associations between dietary patterns or factors and α- or β-diversity. At the phylum level, increasing HEI scores were inversely associated with relative abundance of Actinobacteria, and added sugar was inversely associated with abundance of Verrucomicrobia. Veterans largely consumed a Western-style diet, characterised by poor adherence to nutritional guidelines.

448. Impact of Doxycycline Prophylaxis on Skin and Soft-Tissue Infection Incidence in Naval Special Warfare Trainees

BackgroundSkin and soft-tissue infections (SSTIs) are a common complication of military training. Naval Special Warfare (NSW) training requires prolonged periods of extreme physical exertion and unique environmental exposures, including extended immersion in ocean water. A centerpiece of SEAL training is referred to as “Hell Week” (HW), a colloquial term to reflect the intense physical obstacles and exposure to extreme environmental conditions endured by candidates. Due to such environmental exposures, NSW trainees are at increased risk for SSTI due to uncommon organisms. A prior outbreak of Shewanella SSTI and bacteremia among NSW trainees led to the initiation of prophylactic doxycycline 100 mg daily during and for 7 days after HW to attempt to reduce this risk. The efficacy of this intervention is undetermined.MethodsDoxycycline prophylaxis was initiated in August 2015. We conducted a retrospective analysis of SSTI incidence presenting for medical attention among NSW trainees from April 2013 to November 2018, using case records collected prospectively at the Naval Special Warfare Center. The incidence of SSTI was calculated based on the size of a given class and the number of affected trainees. SSTI cases were then divided and analyzed as occurring during vs. after HW.ResultsThe pre-intervention cohort consisted of 1626 NSW trainees. A total of 76 trainees developed SSTI, with 20 cases during HW and 56 cases in the post-HW period. In the post-intervention cohort, 2022 trainees experienced a total of 81 cases of SSTI during HW and 83 in the post-HW period. 45% of all SSTI cases occurred in the months of June, July, and August. The incidence of cellulitis between the pre- and post-intervention cohorts during HW was 2% and 4%, respectively, and 5% and 6.4% in the post-HW period. There were no hospitalizations for invasive gram-negative infections following the initiation of doxycycline prophylaxis.ConclusionDoxycycline prophylaxis does not appear to reduce the incidence of SSTI but may reduce the incidence of certain severe infections. The choice of antibiotic prophylaxis and dosing may require further investigation. Seasonality of SSTI among NSW trainees is an unexpected finding and may provide valuable information for the prevention of future illness. Disclosures All authors: No reported disclosures.

2143. Attempting to Add Clarity to “Indeterminates” on a Deployed Rapid Diagnostic with Antimicrobial Stewardship Program (ASP) Intervention

BackgroundRapid diagnostic testing paired with ASP intervention optimizes therapy and improves outcomes but few data guide ASP response in the absence of organism identification (ID). We describe the microbiology for organisms unidentified by Accelerate Pheno™ Gram-negative platform (AXDX) in order to inform ASP-provider team communication (PTC).MethodsConsecutive, non-duplicate inpatient blood cultures with Gram-negative bacilli (GNB) following AXDX implementation at a single university hospital between April 2018 and March 2019 were included. Standard of care (SOC) ID and susceptibility followed AXDX. Clinical Microbiology emailed AXDX results to the ASP in real time; results were released into the EMR paired with telephone PTC or withheld after ASP review. Bloodstream Infections (BSIs) and patient outcomes for organisms labeled no/indeterminate ID by the AXDX were characterized.ResultsAXDX was performed on 351 blood cultures. Among 52 (15%) labeled no/indeterminate ID, SOC methods revealed: Enterobacteriaceae (40%; 9 monomicrobial with AXDX targets), anaerobes (21%), non-lactose fermenters (NLFs) other than Pseudomonas aeruginosa (21%), and fastidious GNB (10%). Frequent organisms without AXDX targets included: Raoultella planticola (4); Bacteroides fragilis, Cupriavidus spp., Haemophilus spp., Prevotella spp., Providencia spp., non-aeruginosa Pseudomonas spp., Salmonella spp. (3 each); Pasteurella multocida, Stenotrophomonas maltophilia (2 each). BSI sources were most commonly intra-abdominal (21%), central line-associated (17%), or unknown (17%). CLABSIs were associated with immune suppression and/or substance abuse in all but 1 case. BSIs without active empiric therapy included: NDM-producing Providencia stuartii SSSI; OXA-48-producing R. planticola intraabdominal infection (IAI); Pandoraea spp. CLABSI after liver transplant; enteric fever; B. fragilis, Leptotrichia wadei, and S. maltophilia, each of unknown source. In-hospital mortality occurred in 4 of these cases.ConclusionWhen AXDX yields no/indeterminate ID, ASP chart review for possible anaerobic/IAI, unique environmental exposures, and travel history may assist in guiding empiric therapy. GNB with AXDX targets are not excluded.Disclosures All authors: No reported disclosures.

Study Design and Rationale for the Mood and Methylation Study: A Platform for Multi-Omics Investigation of Depression in Twins.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future 'multi-omic' analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other 'omic' factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

Adiposity, Prediabetes and Diabetes in Foreign versus Native Blacks in the United States

IntroductionBlacks in the United States (U.S.) face a disproportionately high burden of diabetes. The foreign‐born are a growing subgroup of blacks who have had unique environmental exposures. Possible heterogeneity in adiposity and dysglycemia (diabetes and prediabetes) between native and foreign blacks is understudied. This is in large part due to the paucity of datasets with biochemical assessment of disease, anthropometric measures and an adequate sample size of foreign‐born blacks. Pooling two national studies, we created a large dataset of U.S. blacks to examine differences in diabetes and prediabetes by nativity, and the contribution of adiposity in explaining these differences.MethodsWe concatenated data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with five cycles of the National Health and Nutrition Examination Survey (NHANES) 2005–2014, restricting our analysis to those self‐identifying as black. Diabetes was defined as previous physician diagnosis, use of glucose lowering medication, fasting glucose ≥ 126 mg/dL or non‐fasting glucose ≥ 200 mg/dL. Prediabetes was defined as fasting glucose 100–125 mg/dL and non‐fasting glucose 140–199 mg/dL. We compared Body Mass Index (BMI), Waist Circumference (WC), crude prevalence of diabetes and prediabetes by nativity using t‐tests and chi‐squared tests. Using polytomous regressions, we estimated the prevalence ratio of nativity on dysglycemia while adjusting for age and adiposity (BMI and WC). All models additionally control for data source to account for unmeasured differences in study methods.ResultsCharacteristics of native versus foreign blacks are presented in Table 1. Mean age and BMI were significantly lower in foreign black men and women than their native counterparts. Mean WC was significantly lower in foreign black men than native black men. Crude prevalence of diabetes and prediabetes was not significantly different by nativity. Associations of nativity with dysglycemia using native blacks as referent is presented in Figure 1. Adjusting for age and WC, the prevalence ratio of diabetes comparing foreign black women to native black women was statistically significant (PR= 1.22, 95% CI: 1.02, 1.45).ConclusionsThe crude prevalence of dysglycemia was similarly high in foreign‐born and native‐born blacks, even though foreign‐born blacks had significantly lower adiposity. This susceptibility in foreign blacks may be due to a heightened metabolic response to obesity or presence of other obesity‐unrelated risk factors. Further understanding of these factors can inform targeted prevention strategies. Characteristics of Native versus Foreign Blacks in a Pooled Sample from REGARDS and NHANES Men Native Black (n=5411) Foreign Black (n=228) p‐value Age (year) 61.90 (61.57, 62.22) 56.10 (54.13, 58.07) <0.01 BMI (kg/m2) 29.14 (28.99, 29.29) 27.26 (26.69, 27.84) <0.01 Waist circumference (cm) 100.3 (99.87, 100.70) 95.27 (93.77, 96.77) <0.01 % Diabetes 32.45 (31.20, 33.70) 31.58 (25.55, 37.61) 0.78 % Prediabetes 18.28 (17.25, 19.31) 22.37 (16.96, 27.78) 0.12 Women Native Black (n=8191) Foreign Black (n=200) p‐value Age (year) 62.02 (61.77, 62.28) 56.35 (54.38, 58.31) <0.01 BMI (kg/m2) 32.01 (31.85, 32.17) 30.26 (29.43, 31.09) <0.01 Waist circumference (cm) 97.84 (97.50, 98.19) 96.31 (94.36, 98.26) 0.18 % Diabetes 29.80 (28.81, 30.79) 36.00 (29.35, 42.65) 0.06 % Prediabetes 16.65 (15.85, 17.46) 21.50 (15.81, 27.19) 0.07

Food Allergy: International and Developing World Perspectives

Epidemiological data on food allergy worldwide suffer from the challenges of variability in methods of diagnosis, sampling, and response rates. There are little data on food allergy in the developing world and populations with food allergy in such settings may suffer from challenges that are different from those experienced by subjects with food allergy in the developed world. Data based on IgE-mediated food allergy established by food challenge in unselected childhood populations exist only from the USA, Europe, China, Thailand, Australia, and South Africa. In the developing world, barriers to food allergy diagnosis and care include lack of public awareness of food allergy, poor education of health care providers, under- and over-diagnosis of food allergy, lack of access to care, inadequate availability and affordability of testing, insufficient trained health care providers and emergency medication, inadequate labeling legislation, poor availability of food substitutes, and cultural or language issues. Recent data question the use of internationally derived 95 % positive predictive values of specific IgE and skin prick tests for food challenge outcome in children in developing world settings. The little data on food allergy from rural and developing world settings suggest that the prevalence may be lower but challenges experienced by patients may be higher than that in the urban developed world. Differences in food sensitization and food allergy rates between populations may reflect genetic variation, unique environmental exposures or both, via epigenetic modulation.

Lung Cancer Risk, Genetic Variation, and Air Pollution

Large-scale multinational genome-wide association studies (GWAS) of the genetic variation associated with lung cancer initially found that the 5p15.33, 6p21.33, and 15q25 regions were associated with risk of lung cancer among smokers (Amos et al., 2008, Hung et al., 2008). Interestingly, unique regions including 10q25.2, 6q22.2 and 6p21.32 were associated with lung cancer risk in those who had never smoked (Lan et al., 2012), suggesting that the risk variants for non-smoking related lung cancer were distinct from those for smoking related lung cancer. Given that tobacco smoking is the leading risk factor for lung cancer, it stands to reason that lung cancer in those that abstain from tobacco use would have additional novel risk factors which might include genetics or environmental exposures. Some of the main non-tobacco exposures associated with lung cancer are household air pollution, radon, occupational exposures, and outdoor air pollution (Alberg and Samet, 2003). Among the a priori regions identified by Lan et al.'s GWAS of never smokers, significant gene–environment interactions with household air pollution (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04) were identified, thus suggesting that the risk of lung cancer associated with household air pollution exposure varied with the respective alleles for these regions. This study and other similar genetic studies provide evidence that the relationships between airborne exposures and genetic variation may contribute to lung cancer among non-smoking individuals.

Military service and lung disease.

Lung diseases associated with military service are often a reflection of the conditions seen in the local civilian population, and with a few notable exceptions, are often related to unique environmental and occupational exposures. This article reviews important pulmonary diseases that have been associated with military service in the past 100 years in a question-and-answer format. Traditionally, bacterial and viral pneumonias were the most common sources of military morbidity and mortality. With improved preventive medicine and antimicrobial therapy, other diseases related to battlefield injuries or inhalational exposures have assumed greater importance. The etiology of military morbidity and mortality has evolved over the past century. Many of the discoveries related to vaccine efficacy, trauma resuscitation, interstitial lung disease, and even carcinomas have a strong military association.

The contributions of near work and outdoor activity to the correlation between siblings in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study.

We determined the correlation between sibling refractive errors adjusted for shared and unique environmental factors using data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Refractive error from subjects' last study visits was used to estimate the intraclass correlation coefficient (ICC) between siblings. The correlation models used environmental factors (diopter-hours and outdoor/sports activity) assessed annually from parents by survey to adjust for shared and unique environmental exposures when estimating the heritability of refractive error (2*ICC). Data from 700 families contributed to the between-sibling correlation for spherical equivalent refractive error. The mean age of the children at the last visit was 13.3 ± 0.90 years. Siblings engaged in similar amounts of near and outdoor activities (correlations ranged from 0.40-0.76). The ICC for spherical equivalent, controlling for age, sex, ethnicity, and site was 0.367 (95% confidence interval [CI] = 0.304, 0.420), with an estimated heritability of no more than 0.733. After controlling for these variables, and near and outdoor/sports activities, the resulting ICC was 0.364 (95% CI = 0.304, 0.420; estimated heritability no more than 0.728, 95% CI = 0.608, 0.850). The ICCs did not differ significantly between male-female and single sex pairs. Adjusting for shared family and unique, child-specific environmental factors only reduced the estimate of refractive error correlation between siblings by 0.5%. Consistent with a lack of association between myopia progression and either near work or outdoor/sports activity, substantial common environmental exposures had little effect on this correlation. Genetic effects appear to have the major role in determining the similarity of refractive error between siblings.

Wheat-dependent exercise-induced anaphylaxis: a retrospective case review from a tertiary hospital

BackgroundWheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy caused by the combination of wheat ingestion and physical exercise and has been reported in other parts of Asia....

The Genetic Architecture of Type 2 Diabetes Pharmacotherapy: The Emerging Genomic Evidence

Response to anti-diabetic medications is not always predictable or favourable even in phenotypically similar type-2 diabetes (T2D) cases. This is not only due to patient's compliance and access to care but is also considered to be an effect of idiosyncratic differences among individuals, stemming from the combination of their unique genetic background and environmental exposures. In this systematic review, we aimed to summarise the available evidence on pharmacogenetic and pharmacogenomic studies of oral agents for T2D that are currently in the market and describe the agents studied, the targeted loci in regards to the efficacy and the toxicity profile of the agents included. We included 53 studies published between 2003-2012, which examined the following anti-diabetic classes: sulphonylureas, metformin, metiglinides and thiazolidenediones. There were no published studies on newer agents (e.g. incretin based treatments). Forty-nine studies (92.5%) examined the therapeutic response to oral antiglycaemic agents. Outcomes assessed included changes in metabolic markers (fasting or postprandial blood glucose, fasting or postprandial insulin, HbA1c), Homeostasis Assessment Model (HOMA)-Insulin Resistance (IR) or HOMA-B-cell function (HOMA-B), and time to monotherapy failure. Regarding side effects, hypoglycaemia and TZD-related oedema were the most commonly assessed. In the vast majority of the studies included (n=38, 71.7%), more than one outcomes (n=27, 50.9%) and/or more than one SNPs (n=21, 39.6%) were evaluated in the same publication, but most studies examined one drug (n=50, 94.3%). A considerable number of the proposed genes seem to be related to beta-cell development and function, but there are several genes whose underlying pathway linked to diabetes pharmacotherapy remains poorly understood. Pharmacogenomics are still not in pace with the wealth of information provided by GWAS in the genetics of T2D and related traits and the proposed associations need further validation in well-characterized large studies of varying ancestral origins.

A-29 Thematic Poster - Vascular Control

Over the past 14 years, it has been shown that the regulation of physical activity is primarily influenced by genetic/biological mechanisms (25-92% influence) and unique environmental exposures (8-52% influence) with little to no common environmental influence. However, it is not known whether an interaction between biological mechanisms and environmental exposures play a significant regulatory role in physical activity. PURPOSE: To investigate whether environmental endocrine disruptors (ED) alter wheel-running activity in mice. METHODS: We randomly assigned 3 pregnant female C57Bl/6J inbred mice to one of three groups: ED by Bisphenol-A (BPA), ED by benzyl butyl phthalate (BBP), or saline/control. All pregnant mice received an intraperitoneal injection on gestation days 9-16 to disrupt androgen receptor formation. Pups (BPA, n=6; BBP, n=2; control, n=3) were weaned at 3 weeks of age and placed in individual cages with running wheels. Daily distance, duration, and speed was measured for 6 weeks. Mouse weight (g) was measured weekly. RESULTS: There were no significant differences observed in any of the physical activity indices (distance, p=0.54; duration, p=0.45; and speed, p=0.28). BPA (p=0.0006) and BBP (p=0.0003) female mice weighed significantly less than controls at 3 weeks of age and BBP (0.0361) male mice weighed significantly less than controls at 3 weeks of age. BPA (p=0.0395) and BBP (p=0.0132) female mice weighed significantly less than controls at 9 weeks of age. Unlike previous studies, there was a positive significant correlation (p=0.0074) between weight and distance. CONCLUSIONS: While our results did not show a direct relationship between ED and physical activity, unlike previous studies, we showed a positive correlation between weight and distance suggesting ED may affect this relationship. These results - albeit limited in sample size and statistical power - initially suggest that there may be indirect effects of prenatal ED on physical activity and the relationship to body weight. Funded by a Pilot Grant from the Center for Translational Environmental Health Research at Texas A&M University.

Comparison of the Etiology of Viral Respiratory Illnesses in Inner-City and Suburban Infants

Background. The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct. Methods. We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction. Results. Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%–21%), compared with Madison (6%). Conclusions. These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population.