A complete Protocadherin-19 ectodomain model for evaluating epilepsy-causing mutations and potential protein interaction sites.

Cadherin superfamily members play a critical role in differential adhesion during neurodevelopment, and their disruption has been linked to several neurodevelopmental disorders. Mutations in protocadherin-19 (PCDH19), a member of the δ-protocadherin subfamily of cadherins, cause a unique form of epilepsy called PCDH19 clustering epilepsy. While PCDH19 and other non-clustered δ-protocadherins form multimers with other members of the cadherin superfamily to alter adhesiveness, the specific protein surfaces responsible for these interactions are unknown. Only portions of the PCDH19 extracellular domain structure had been solved previously. Here, we present a structure of the missing segment from zebrafish Protocadherin-19 (Pcdh19) and create a complete ectodomain model. This model shows the structural environment for 97% of disease-causing missense mutations and reveals two potential surfaces for intermolecular interactions that could modify Pcdh19's adhesive strength and specificity.

Influence of Work on Elevated Blood Pressure in Hispanic Adolescents in South Texas.

Literature supports an association between work and cardiovascular disease in adults. The objective of this study was to examine the relationship between current work status and elevated blood pressure in Hispanic adolescents. Participants were students in Hidalgo County, located along the Texas-Mexico border. Participants enrolled in the cohort study in ninth grade with assessments completed once a year for up to three years. Participants completed a self-report survey, while staff measured height, weight, waist circumference, blood pressure, and were screened for acanthosis nigricans. A generalized linear regression model with a logit link function was constructed to assess current work status and elevated blood pressure. Of the 508 participants, 29% had elevated blood pressure, which was associated with being male and other chronic disease indicators (e.g., acanthosis nigricans, overweight/obesity). The mean probability for elevated blood pressure was higher among currently working adolescents compared to those who were not. Findings were statistically significant (p < 0.05) at baseline. The findings illustrate that a large proportion of adolescents along the Texas-Mexico border may have elevated blood pressure and that working may be associated with it. Subsequent research is needed to confirm these findings, as well as to identify the mechanism for how work may increase hypertension in adolescents.

A Randomized Trial of Contingency Management for Smoking Cessation During Intensive Outpatient Alcohol Treatment.

INTRODUCTION: This randomized clinical trial was designed to evaluate the efficacy of contingency management (CM) for smoking cessation for smokers with alcohol abuse or dependence delivered concurrently with intensive outpatient alcohol treatment. The study also explored the indirect effects of CM smoking treatment and smoking cessation on alcohol and drug use outcomes. METHODS: Alcohol abuse/dependent smokers were randomized to cognitive behavioral therapy plus nicotine replacement therapy plus contingency management (CBT+NRT+CM) or to cognitive behavior therapy plus nicotine replacement therapy (CBT+NRT) delivered concurrent with a three-week intensive outpatient alcohol treatment program. RESULTS: Participants in the CBT+NRT+CM condition were significantly more likely to be cigarette abstinent at the end of treatment (χ2(1)=8.48, p=.004) with approximately double the carbon monoxide confirmed quit rate (60%) compared with the CBT+NRT condition (29%). At the one-month and six-month time-points there were nonsignificant differences in smoking abstinence outcomes by condition. Smoking treatment condition did not directly affect alcohol abstinence outcomes, but we observed an indirect effect of smoking treatment on alcohol and drug abstinence at one-month follow-up that was mediated by smoking cessation at the end of treatment. CONCLUSIONS: Adding CM to an evidence-based smoking cessation treatment that included medication and behavioral counseling doubled the quit rate at the end of treatment. This finding provides strong evidence for the efficacy of CM for helping alcohol dependent smokers reach the milestone of initial smoking abstinence.

Completion of Multidisciplinary Treatment for Persistent Postconcussive Symptoms Is Associated With Reduced Symptom Burden.

OBJECTIVE: To investigate the pre- to posttreatment changes in both posttraumatic stress disorder (PTSD) and persistent postconcussive symptoms (PPCSs). SETTING AND PARTICIPANTS: We studied 257 active-duty patients with a history of mild traumatic brain injury (mTBI) who completed multidisciplinary outpatient treatment at Brooke Army Medical Center TBI Clinic from 2008 to 2013. This treatment program included cognitive rehabilitation; vestibular interventions; headache management; and integrated behavioral healthcare to address co-occurring psychiatric conditions such as PTSD, depression, and sleep disturbance. DESIGN: A 1-group; preexperimental, pre- to posttreatment study. MAIN MEASURES: The Neurobehavioral Symptom Inventory (NSI) was used to assess PPCSs, and the PTSD Checklist-Military Version (PCL-M) was used to asses PTSD symptoms. RESULTS: Global PPCS resolution (mean NSI: 35.0 pre vs 23.8 post; P < .0001; d = 0.72) and PTSD symptom resolution (mean PCL-M: 43.2 pre vs 37.7 post; P < .0001; d = 0.34) were statistically significant. Compared with those with only mTBI, patients with mTBI and PTSD reported greater global PPCS impairment both pretreatment (mean NSI: 48.7 vs 27.9; P < .0001) and posttreatment (mean NSI: 36.2 vs 17.4; P < .0001). After adjusting for pretreatment NSI scores, patients with comorbid PTSD reported poorer PPCS resolution than those with mTBI alone (mean NSI: 27.9 pre vs 21.7 post; P = .0009). CONCLUSION: We found a reduction in both self-reported PPCSs and PTSD symptoms; however, future studies are needed to identify specific components of care associated with symptom reduction.

"The Only Thing I Wish I Could Change Is That They Treat Us Like People and Not Like Animals": Injury and Discrimination Among Latino Farmworkers.

OBJECTIVE: This article describes how perceived discrimination shapes the way Latino farmworkers encounter injuries and seek out treatment. METHODS: After 5 months of ethnographic fieldwork, 89 open-ended, semistructured interviews were analyzed. NVivo was used to code and qualitatively organize the interviews and field notes. Finally, codes, notes, and co-occurring dynamics were used to iteratively assess the data for major themes. RESULTS: The primary source of perceived discrimination was the "boss" or farm owner. Immigrant status was also a significant influence on how farmworkers perceived the discrimination. Specifically, the ability to speak English and length of stay in the United States were related to stronger perceptions of discrimination. Finally, farm owners compelled their Latino employees to work through their injuries without treatment. CONCLUSIONS: This ethnographic account brings attention to how discrimination and lack of worksite protections are implicated in farmworkers' injury experiences and suggests the need for policies that better safeguard vulnerable workers.

U.S. military service and the prevalence of metabolic syndrome: Findings from a cross-sectional analysis of the Cooper Center Longitudinal Study, 1979-2013.

U.S. military service confers both health benefits and risks potentially associated with a clustering of cardiovascular risk factors called metabolic syndrome. However, the association between prior military service and metabolic syndrome has not sufficiently been examined. The purpose of the study was to compare the prevalence of metabolic syndrome by prior military service status. Among 42,370 men (887 with prior military service) examined from 1979 to 2013 at the Cooper Clinic (Dallas, TX), we used a cross-sectional study design to examine the association between military service and metabolic syndrome. First, an unadjusted log binomial regression model was performed by regressing the prevalence of metabolic syndrome on prior service. This was followed by performing Kleinbaum's modeling strategy for assessing confounding. The same methodology was used to explore the association between individual metabolic syndrome risk factors and prior service. Prior military service was not significantly associated with the prevalence of metabolic syndrome (PR=0.98, 0.89-1.07). None of the variables explored were identified as confounders. Participants with prior military service had lower prevalence of both elevated levels of triglycerides (PR=0.89, 0.80-0.99) and low levels of high-density lipoprotein-cholesterol (PR=0.78, 0.70-0.88). They had a higher prevalence of elevated resting systolic blood pressure (PR=1.23, 1.12-1.35). However, none of these associations were significant after adjusting for identified confounders: age; cardiorespiratory fitness; and exam year. Study findings indicate that military service was not independently associated with the prevalence of metabolic syndrome or its components. Future research is warranted longitudinally assessing the impact of military service on long-term outcomes.

Structural determinants of adhesion by Protocadherin-19 and implications for its role in epilepsy.

Non-clustered δ-protocadherins are homophilic cell adhesion molecules essential for the development of the vertebrate nervous system, as several are closely linked to neurodevelopmental disorders. Mutations in protocadherin-19 (PCDH19) result in a female-limited, infant-onset form of epilepsy (PCDH19-FE). Over 100 mutations in PCDH19 have been identified in patients with PCDH19-FE, about half of which are missense mutations in the adhesive extracellular domain. Neither the mechanism of homophilic adhesion by PCDH19, nor the biochemical effects of missense mutations are understood. Here we present a crystallographic structure of the minimal adhesive fragment of the zebrafish Pcdh19 extracellular domain. This structure reveals the adhesive interface for Pcdh19, which is broadly relevant to both non-clustered δ and clustered protocadherin subfamilies. In addition, we show that several PCDH19-FE missense mutations localize to the adhesive interface and abolish Pcdh19 adhesion in in vitro assays, thus revealing the biochemical basis of their pathogenic effects during brain development.

The impact of hearing impairment and noise-induced hearing injury on quality of life in the active-duty military population: challenges to the study of this issue.

The objectives of this research were to 1) summarize the available evidence on the impact of hearing loss on quality of life (QOL) among U.S. active-duty service members, 2) describe the QOL instruments that have been used to quantify the impact of hearing loss on quality of life, 3) examine national population-level secondary databases and report on their utility for studying the impact of hearing loss on QOL among active-duty service members, and 4) provide recommendations for future studies that seek to quantify the impact of hearing loss in this population. There is a lack of literature that addresses the intersection of hearing impairment, the military population, and quality of life measures. For audiological research, U.S. military personnel offer a unique research population, as they are exposed to noise levels and blast environments that are highly unusual in civilian work settings and can serve as a model population for studying the impact on QOL associated with these conditions. Our team recommends conducting a study on the active-duty service member population using a measurement instrument suitable for determining decreases in QOL specifically due to hearing loss.

Economic Burden of Hearing Loss for the U.S. Military: A Proposed Framework for Estimation.

The goal of this multiphased research is to develop methods to comprehensively determine the economic impact of hearing impairment and noise-induced hearing injury among active duty U.S. Service Members. Several steps were undertaken to develop a framework and model for economic burden analysis: (1) a literature review identifying studies reporting the cost of health conditions and injuries in the Department of Defense, (2) consultation with a panel of subject matter experts who reviewed these cost items, and (3) discussions with DoD data stewards and review of relevant data dictionaries and databases. A Markov model was developed to represent the cumulative economic effect of events along the career span, such as retraining after hearing impairment and injury, by synthesizing inputs from various sources. The model, as developed and proposed in this study, will be a valuable decision-making tool for the DoD to identify high-risk groups, take proactive measures, and develop focused education, customized equipping, and return-to-duty and reintegration programs, thereby maximizing the retention of skilled, experienced, and mission-ready Service Members.

Heat effects among migrant and seasonal farmworkers: a case study in Colorado.

BACKGROUND: Although migrant and seasonal farmworkers are highly vulnerable to ambient heat because of their working conditions, heat effects in this population have been rarely studied. OBJECTIVES: We estimated effects of heat on mean daily counts of clinic visits among migrant and seasonal farmworkers by taking advantage of a unique longitudinal medical records database in the USA. METHODS: We compiled a daily weather and clinic visit data set based on data from a health centre in Colorado for the summer of 2013. A total of 14 481 patients were included in our analysis, including 150 migrant farmworkers and 231 seasonal farmworkers with an average of 3 and 4 visits per day. We used Poisson regression to estimate the associations between heat and daily all-cause or cardiovascular-specific clinic visits among migrant or seasonal farmworkers or other stratified patients. We defined heat effects as the percentage difference in average daily counts of clinic visits, comparing 90-50th centiles of daily mean apparent temperature, a composite index accounting for both temperature and humidity. We conducted a sensitivity analysis to evaluate the impact of adjustment for ozone levels and different heat definitions. RESULTS: Estimates of heat effects on average daily clinic visits among migrant farmworkers were positive (88.0%, 95% CI: 26.2% to 180.0%). We did not observe statistically significant associations between heat and clinic visits among other stratified groups. CONCLUSIONS: Our study appears to be the first to link heat effects with clinic data among migrant and seasonal farmworkers. This research suggests possible significant impact of heat on migrant farmworkers and provides justifications for further studies.

Cardiovascular Disease Risk Factors in Hispanic Adolescents in South Texas.

OBJECTIVES: Despite a national crisis of increased prevalence of obesity and type 2 diabetes mellitus in adolescents, especially among Hispanics, there is a paucity of data on health indicators among farmworker adolescents and their peers. The main aim of this study was to estimate the prevalence of cardiovascular disease risk factors in a population of Hispanic adolescent students in south Texas. The study also aimed to compare the prevalence of these risk factors between students enrolled in the Migrant Education Program (MEP) and other students, and between boys and girls. METHODS: In partnership with the Weslaco (Texas) Independent School District and the Migrant Education Department, a cohort study was conducted from 2007 to 2010 to estimate the prevalence of overall obesity (body mass index ≥85th percentile for age and sex), abdominal obesity (waist circumference ≥75th percentile for age, sex, and ethnicity), acanthosis nigricans (AN), and high blood pressure (HBP; ≥90th percentile for age, height, and sex or systolic/diastolic BP ≥120/80 mm Hg) among MEP students compared with other students from two south Texas high schools. Multilevel logistic regression was used to assess the relation between sex and our main outcomes of interest while accounting for within-school nesting of participants. RESULTS: Among 628 sampled students, 508 (80.9%) completed the consent procedure and participated in the study. Of these, 257 were MEP students and 251 were non-MEP peers. Approximately 96.7% of participants were Hispanic and 50.0% were boys. Analyses of data across the years comparing MEP students and non-MEP students show an average prevalence of 44.8% versus 47.7% for overall obesity, 43.2% versus 43.7% for abdominal obesity, 24.7% versus 24.7% for AN, and 29.2% versus 32.8% for HBP. Across recruitment and follow-up years, the prevalence of overall obesity, abdominal obesity, and HBP was 1.3 to 1.5, 1.2 to 1.8, and 2.9 to 4.6 times higher in boys than in girls, respectively. In contrast, the prevalence of AN varied little by sex. CONCLUSIONS: The high prevalence of cardiovascular risk factors in both groups suggests a compelling need for comprehensive, culturally targeted interventions to prevent future cardiovascular diseases in these high-risk Hispanic adolescents, especially among boys. There were not, however, substantial differences between MEP students and other students. These findings also support the feasibility of conducting future epidemiologic studies among adolescent farmworkers and their families, as well as culturally appropriate school or community-based interventions.

The Feasibility of Using Electronic Health Records to Describe Demographic and Clinical Indicators of Migrant and Seasonal Farmworkers.

Few extensive, national clinical databases exist on the health of migrant and seasonal farmworkers (MSFWs). Electronic health records (EHRs) are increasingly utilized by Federally Qualified Health Centers (FQHCs) and have the potential to improve clinical care and complement current surveillance and epidemiologic studies of underserved working populations, such as MSFWs. The aim of this feasibility study was to describe the demographics and baseline clinical indicators of patients at an FQHC by MSFW status. The authors described 2012 patient demographics, social history, medical indicators, and diagnoses by MSFW status from the de-identified EHR database of a large, multisite Colorado Migrant Health Center (MHC). Included in the study were 41,817 patients from 2012: 553 (1.3%) MSFWs, 20,665 (49.4%) non-MSFWs, and 20,599 (49.3%) who had no information in the MSFW field. MSFWs were more often male, married, employed, Hispanic, and Spanish-speaking compared with non-MSFWs. The most frequent diagnoses for all patients were hypertension, overweight/obesity, lipid disorder, type 2 diabetes, or a back disorder. Although there were significant missing values, this feasibility study was able to analyze medical data in a timely manner and show that Meaningful Use requirements can improve the usability of EHR data for epidemiologic research of MSFWs and other patients at FQHCs. The results of this study were consistent with current literature available for MSFWs. By reaching this vulnerable working population, EHRs may be a key data source for occupational injury and illness surveillance and research.

Protocadherins control the modular assembly of neuronal columns in the zebrafish optic tectum.

Cell-cell recognition guides the assembly of the vertebrate brain during development. δ-Protocadherins comprise a family of neural adhesion molecules that are differentially expressed and have been implicated in a range of neurodevelopmental disorders. Here we show that the expression of δ-protocadherins partitions the zebrafish optic tectum into radial columns of neurons. Using in vivo two-photon imaging of bacterial artificial chromosome transgenic zebrafish, we show that pcdh19 is expressed in discrete columns of neurons, and that these columnar modules are derived from proliferative pcdh19(+) neuroepithelial precursors. Elimination of pcdh19 results in both a disruption of columnar organization and defects in visually guided behaviors. These results reveal a fundamental mechanism for organizing the developing nervous system: subdivision of the early neuroepithelium into precursors with distinct molecular identities guides the autonomous development of parallel neuronal units, organizing neural circuit formation and behavior.

Three cocrystals and a cocrystal salt of pyrimidin-2-amine and glutaric acid.

Four new cocrystals of pyrimidin-2-amine and propane-1,3-dicarboxylic (glutaric) acid were crystallized from three different solvents (acetonitrile, methanol and a 50:50 wt% mixture of methanol and chloroform) and their crystal structures determined. Two of the cocrystals, namely pyrimidin-2-amine-glutaric acid (1/1), C4H5N3·C6H8O4, (I) and (II), are polymorphs. The glutaric acid molecule in (I) has a linear conformation, whereas it is twisted in (II). The pyrimidin-2-amine-glutaric acid (2/1) cocrystal, 2C4H5N3·C6H8O4, (III), contains glutaric acid in its linear form. Cocrystal-salt bis(2-aminopyrimidinium) glutarate-glutaric acid (1/2), 2C4H6N3(+)·C6H6O4(2-)·2C6H8O4, (IV), was crystallized from the same solvent as cocrystal (II), supporting the idea of a cocrystal-salt continuum when both the neutral and ionic forms are present in appreciable concentrations in solution. The diversity of the packing motifs in (I)-(IV) is mainly caused by the conformational flexibility of glutaric acid, while the hydrogen-bond patterns show certain similarities in all four structures.

Coding of Central Cancer Registry Industry and Occupation Information: The Texas and Louisiana Experiences.

BACKGROUND: Usual industry and occupation text information have been collected by central cancer registries but few have had the resources to code these data, limiting their usefulness for assessing occupational cancer risks. STUDY AIMS: This project was undertaken to use software available from the National Institute for Occupational Safety and Health (NIOSH) to code industry and occupation information in cancer records reported to the Texas Cancer Registry (TCR) and the Louisiana Tumor Registry (LTR) and to assess the feasibility of its use in ongoing registry operations; to assess the quality of the reported information; and to determine its usefulness in occupational cancer research. METHODS: De-identified data files of TCR (n = 103,276) and LTR (n = 26,090) cancer records were obtained for diagnosis years 2010 and 2011, respectively, for cases aged 14 years and older, with industry and occupation text. These data fields were coded to the 2000 US Census Bureau using the NIOSH Industry and Occupation Computerized Coding System (NIOCCS) software at the high level confidence (90% or greater accuracy) and through manual code assignments for records not coded by NIOCCS. RESULTS: NIOCCS assigned a code for 37.2% of TCR records and 59.9% of LTR records. Examination of the quality of the coded data found 44.2% of TCR records and 31.1% of LTR records to have missing, unknown, or otherwise insufficient text for assigning a specific industry and occupation code. Additionally, the vague noninformative category of "retired" was reported for 14.9% and 11.2% of TCR and LTR records, respectively. Records with "homemaker/housewife" or those with terms indicating that they never worked represented 7.2% of TCR cases and 9.7% of LTR cases. Excluding the unknown, never worked, and retired categories, no one specific industry or occupation major grouping represented more than 5% of cases in either of the registries. CONCLUSION: NIOCCS is a helpful tool for coding industry and occupation text and continues to improve, but other registry resources are required for implementation into ongoing operations. Improvement in data quality of reported text information in cancer records is paramount to maximize the efficiency of NIOCCS and improve the availability of coded, specific industry and occupation information for occupational cancer research.

The Department of Defense Epidemiologic and Economic Burden of Hearing Loss study.

Although studies have examined the relation between military-related noise and hearing, comprehensive data to calculate rates of hearing loss across all Services and to determine economic impact are lacking. The goal of the multiphase Department of Defense (DoD) Epidemiologic and Economic Burden of Hearing Loss (DEEBoHL) project is to examine rates of hearing impairment and noise-induced hearing injury, relevant noise exposures, and to determine the economic burden of these outcomes to the DoD and Service Members. The DoD Hearing Center of Excellence is supporting the following Phase I specific aims, among active duty Service Members to (1) calculate rates of hearing impairment and noise-induced hearing injury, and (2) develop a framework for the DoD to conduct comprehensive economic burden studies for hearing impairment and noise-induced hearing injury. The study is led by a multidisciplinary team from The University of Texas School of Public Health, The University of Texas Health Science Center at San Antonio, and The Geneva Foundation, with guidance from experts who make up the study advisory board. In this article, we focus on an overview of the DEEBoHL study, the methods for the first aim of this effort, and describe future plans for the study.

Community based research network: opportunities for coordination of care, public health surveillance, and farmworker research.

INTRODUCTION: The lack of aggregated longitudinal health data on farmworkers has severely limited opportunities to conduct research to improve their health status. To correct this problem, we have created the infrastructure necessary to develop and maintain a national Research Data Repository of migrant and seasonal farmworker patients and other community members receiving medical care from Community and Migrant Health Centers (C/MHCs). Project specific research databases can be easily extracted from this repository. METHODS: The Community Based Research Network (CBRN) has securely imported and merged electronic health records (EHRs) data from five geographically dispersed C/MHCs. To demonstrate the effectiveness of our data aggregation methodologies, we also conducted a small pilot study using clinical, laboratory and demographic data from the CBRN Data Repository from two initial C/MHCs to evaluate HbA1c management. RESULTS: Overall, there were 67,878 total patients (2,858 farmworkers) that were seen by two C/MHCs from January to August 2013. A total of 94,189 encounters were captured and all could be linked to a unique patient. HbA1c values decreased as the number of tests or intensity of testing increased. CONCLUSION: This project will inform the foundation for an expanding collection of C/MHC data for use by clinicians for medical care coordination, by clinics to assess quality of care, by public health agencies for surveillance, and by researchers under Institutional Review Board (IRB) oversight to advance understanding of the needs and capacity of the migrant and seasonal farmworker population and the health centers that serve them. Approved researchers can request data that constitute a Limited Data Set from the CBRN Data Repository to establish a specific research database for their project.