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Objective: To compare dietary intakes between LGBTQ + and non-LGBTQ + college students. Participants: Participants were LGBTQ+ ( n  = 92) and non-LGBTQ+ ( n  = 491) college students. Methods: The 26-item Dietary Screener Questionnaire assessed intakes of added sugars, fiber, whole grains, fruits and vegetables, dairy, and calcium. Percentage of participants meeting Dietary Guidelines for Americans were also computed. Multivariate ANCOVA assessed differences in dietary intake. Chi-square analyses assessed differences in proportions of LGBTQ + and non-LGBTQ + students meeting recommendations. Results: LGBTQ + students reported lower intakes of fiber, whole grains, fruit, and fruits and vegetables both including and excluding French fries (all p  < 0.05). Fewer LGBTQ + students met recommendations for fruit (5.7%) compared to their non-LGBTQ + counterparts (14.2%; p  = .03). Conclusions: LGBTQ + students report poorer indices of diet quality compared to non-LGBTQ + students. Health promotion programming efforts to improve these outcomes may need to be tailored differently for students who identify as LGBTQ+.

Stroke is a leading cause of disability in the US, often altering one's ability to access and consume food. The aim of the present study was to characterize and evaluate predictors of stroke survivors' diet quality (DQ). A cross-sectional evaluation of 2011-2018 National Health and Nutrition Examination Survey data is presented. Stroke survivors (n = 632) were matched for age, gender, and race with neurologically intact controls (n = 913). Food group intake, key nutrient intake, and Healthy Eating Index (HEI)-2015 scores were calculated from two 24-hour recalls and evaluated in relation to history of stroke, education, presence of a partner in the home, and income. Group differences in and predictors of DQ were evaluated with weighted independent samples t-tests and linear regression. Stroke survivors had lower intakes of vegetables, dairy, seafood and plant proteins, and unsaturated fats, and lower total HEI-2015 scores ( P < 0.05). Having more education, a partner in the home, and higher income were overall positive predictors of DQ. DQ factors emphasized in heart-healthy diets were low in stroke survivors. Interventions may better address barriers to healthy eating post-stroke by incorporating educational, financial, and social support components., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Author(s).)

Increased dissemination of the CDC's Diabetes Prevention Program (DPP) is imperative to reduce type 2 diabetes. Due to its nationwide reach and mission to improve health, Cooperative Extension (Extension) is poised to be a sustainable DPP delivery system. However, research evaluating DPP implementation in Extension remains scant. Extension professionals delivered the DPP in a single-arm hybrid type II effectiveness-implementation study. Semi-structured interviews with Extension professionals were conducted at three time points. The Consolidated Framework for Implementation Research (CFIR) guided interview coding and analysis. Constructs were rated for magnitude and valence and evaluated as facilitators or barriers of RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) outcomes. The program reached 119 participants, was adopted by 92% (n = 12/13) of trained Extension professionals and was implemented according to CDC standards: all programs exceeded the minimum 22-session requirement (26 ± 2 sessions). The program was effective in achieving weight loss (5.0 ± 5.2%) and physical activity (179 ± 122 min/week) goals. At post-intervention, eight professionals (67%) had begun or planned to maintain the intervention within the next 6 months. Several facilitators were identified, including Extension leadership structure, organizational compatibility, and technical assistance calls. Limited time to recruit participants was the primary barrier. Positive RE-AIM outcomes, facilitated by contextual factors, indicate Extension is an effective and sustainable DPP delivery system. Extension and other DPP implementers should plan strategies that promote communication, the program's evidence-base, recruitment time, and resource access. Researchers should explore DPP implementation in real-world settings to determine overall and setting-specific best practices, promote intervention uptake, and reduce diabetes., (© 2023. The Author(s).)

Purpose: Stroke is a leading cause of long-term disability in the US, yet a feasible assessment measure with predictive value for components of the International Classification of Functioning, Disability, and Health (ICF) Core Set for Stroke is lacking. The purpose of the present study was to explore the predictive value of potential assessment measures on factors within each ICF component in stroke survivors., Materials and Methods: Demographic, anthropometric, blood-based biomarker, physical functioning, and Global Physical Activity Questionnaire data were collected on stroke survivors in the 2011-2018 NHANES cycles. Potential predictors (handgrip strength relative to weight, age, sex, race, education level, marital status, poverty ratio, stroke chronicity) of physical function, activities of daily living (ADLs), participation in social activities, metabolic syndrome, and meeting physical activity recommendations were evaluated using weighted linear and ordinal logistic regression., Results: Relative handgrip strength was a significant predictor of physical function, difficulty participating in ADLs and social activities, and odds of meeting physical activity recommendations. As relative handgrip strength increased, these factors improved among stroke survivors., Conclusions: To decrease disability rates and optimize function among stroke survivors, the use of assessment measures like relative handgrip strength that may predict multiple ICF components is warranted.

Objective: The effectiveness of the National Diabetes Prevention Program (DPP) in improving diet quality (DQ) in community settings is largely unknown. This study aimed to evaluate the DQ changes of Extension DPP participants., Methods: A single-group, repeated-measures design was used to evaluate an Extension-implemented DPP using the PreventT2 curriculum. Participants were overweight adults with or at high risk for prediabetes (n = 88). Weight and DQ (Healthy Eating Index-2015, Dietary Screener Questionnaire) were evaluated using mixed-effects regression., Results: There was no change in the Healthy Eating Index-2015 total score. Predicted fiber, fruit, and vegetable intake increased (P < 0.05) but remained below recommendations., Conclusions and Implications: Clinically meaningful DQ changes of Extension DPP participants were limited. The effect of the DPP on DQ in Extension and other implementation settings should be evaluated through randomized controlled trials. Diabetes Prevention Program curriculum revisions that include more specific dietary goals and educational tools may promote greater DQ changes in DPP participants., (Copyright © 2023 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Sternal closure after median sternotomy traditionally uses a stainless steel wire cerclage. Sternal wires are placed through or around the sternum, and the wire ends are twisted together to bring the sternum back together. Complications of this technique include sternal instability, dehiscence, non-union, and increased pain. Compared to traditional wire cerclage, the Figure 8 FlatWire Sternal Closure System has been demonstrated to be stronger and significantly reduce sternal cut-through and postoperative pain. There was no significant difference in hospital length of stay or mean hospitalization cost. Operative time was slightly longer in the FlatWire group, but this difference has been attributed to the learning curve of mastering the FlatWire technique. This article and supplemental video will demonstrate the technique of FlatWire Sternal Closure System. Briefly, the FlatWire is placed around the sternum, and the FlatWire end is fed through the security box. Once all of the wires are placed, the Figure 8 tensioning device is used to tighten each wire through the security box to the appropriate tensile force. Next, the FlatWires are rotated 90 degrees to hold the sternal position temporarily. Once sternal approximation is achieved, each FlatWire is twisted 120 degrees, and any excess length of the FlatWire is clipped., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-110/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Exercise training (EX) and weight loss (WL) improve lower extremity physical function (LEPF) in older overweight women; however, effects on rate of torque development (RTD) are unknown. This study aimed to determine the effects of WL + EX or WL alone on RTD, and relatedly LEPF, in overweight older women. Leg strength was assessed using isokinetic dynamometry, and RTD was calculated (RTD200 = RTD at 200 ms, RTDPeak = peak RTD, T2P = time to 1st peak). LEPF was determined via clinical functional tasks. Women (n = 44, 69.1 ± 3.6 years, 30.6 ± 4.3 kg/m2) completed a 6-month trial in EX + WL or WL groups with similar weight loss (-9.8 ± 4.2%, p > .95). EX + WL had greater improvements in (a) most LEPF tasks (p < .001) and (b) RTD200, compared with WL (36% vs. -16%, p = .031); no other RTD parameters differed. Changes in RTD parameters and LEPF were not related (all p > .05). RTD is responsive to EX but is not associated with LEPF in older women.

We have modified the HeartMate 3 (Abbott, Abbott Park, IL) implantation technique to better suit our patient population. This modification optimizes the placement of the HeartMate 3 sewing cuff and allows passage of the suture transmurally from endocardium to epicardium in a "cut then sew" technique. We believe this affords a superior seal and protection from tearing friable myocardium., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Flail chest and severely displaced rib fractures due to blunt trauma can be associated with intrathoracic injuries. At our institution, two thoracic surgeons perform all surgical stabilization of rib fractures (SSRF): one performs routine uniportal thoracoscopy (R-VATS) at the time of SSRF and the other for only select cases (S-VATS). In this pilot study, we hypothesized that R-VATS at the time of SSRF identifies and addresses intrathoracic injuries not seen on imaging and may impact patient outcomes., Methods: A retrospective review of all patients who underwent SSRF from 2013-2019 at our institution was performed for severely displaced rib fractures or flail chest. Data collected included demographics, imaging results, treatment strategy, and operative findings., Results: Ninety-nine patients underwent SSRF. Uniportal thoracoscopy was performed on 69% of these patients. When thoracoscopy was performed, 31 additional injuries were identified. R-VATS identified 23 additional intrathoracic findings at time of thoracoscopy not seen on CT scan compared to 8 findings in the S-VATS group (P=0.367). At 3 months follow-up, one empyema and one diaphragmatic hernia required reoperation-neither of which underwent thoracoscopy at time of SSRF. There were no differences in LOS, operative times, and overall mortality between the SSRF/thoracoscopy and SSRF only groups., Conclusions: R-VATS at the time of SSRF did not identify a statistically significant greater number of occult intrathoracic injuries compared to S-VATS. R-VATS was not associated with increased operative time, LOS, and mortality. Further study is needed to determine if there is benefit to R-VATS in patients meeting requirements for rib fracture repair., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2087). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Community-based educational programs can complement clinical strategies to increase cancer screenings and encourage healthier lifestyles to reduce cancer burden. However, implementation quality can influence program outcomes and is rarely formally evaluated in community settings. This mixed-methods study aimed to characterize implementation of a community-based cancer prevention program using the Consolidated Framework for Implementation Research (CFIR), determine if implementation was related to participant outcomes, and identify barriers and facilitators to implementation that could be addressed., Methods: This study utilized quantitative participant evaluation data (n = 115) and quantitative and qualitative data from semi-structured interviews with program instructors (N = 13). At the participant level, demographic data (age, sex, insurance status) and behavior change intention were captured. Instructor data included implementation of program components and program attendance to create a 7-point implementation score of fidelity and reach variables. Degree of program implementation (high and low) was operationalized based on these variables (low: 0-4, high: 5-7). Relationships among degree of implementation, participant demographics, and participant outcomes (e.g., intent to be physically active or limit alcohol) were assessed using linear or ordinal logistic mixed effects models as appropriate. Interview data were transcribed and coded deductively for CFIR constructs, and constructs were then rated for magnitude and valence. Patterns between ratings of high and low implementation programs were used to determine constructs that manifested as barriers or facilitators., Results: Program implementation varied with scores ranging from 4 to 7. High implementation was related to greater improvements in intention to be physically active (p <  0.05), achieve a healthy weight (p <  0.05), and limit alcohol (p <  0.01). Eight constructs distinguished between high and low implementation programs. Design quality and packaging, compatibility, external change agents, access to knowledge and information, and experience were facilitators of implementation and formally appointed internal implementation leaders was a barrier to implementation., Conclusions: As higher implementation was related to improved participant outcomes, program administrators should emphasize the importance of fidelity in training for program instructors. The CFIR can be used to identify barriers and/or facilitators to implementation in community interventions, but results may be unique from clinical contexts.

Polycyclic aromatic hydrocarbons (PAHs) refer to organic compounds that are byproducts of incomplete combustion of fossil fuels and wood. One specific polycyclic aromatic hydrocarbon, 2-aminoanthracene (2AA), is a member of a broader group of compounds known as anthracenes, which have been classified by the United States Agency for Toxic Substances and Disease Registry (ASTDR) as one of a group of PAHs of top concern based on their greater potential risk for exposure and greater harmful effects to humans, compared to other PAHs. Previous research has shown that 2AA affects genes involved in carbohydrate and lipid metabolism, inflammatory stress responses, and immune system responses, among other processes. The objective of the present study was to examine the toxicity of dietary ingestion of 2AA from gestation through the postnatal period. Pregnant dams (Day 1) were purchased from Taconic Hudson, NY, and assigned into dose regimens of 0 mg/kg- (control-C), 50 mg/kg- (low dose-LD) and 100 mg/kg-diet (high dose-HD) 2AA. Dams were fed 2AA contaminated diet during the period of gestation and postpartum. Insulin and H&E immunohistochemical staining were undertaken and indicated no significant changes between control and treated groups. However, percent pancreatic islets (islets within the pancreas) were larger in the exposed groups. The value was 1.5% in the control dams compared to 3.2% and 4.3% low dose and high dose groups respectively. Serum concentrations of albumin and lactate dehydrogenase (LDH) were increased in the exposed groups, with the HD group experiencing the greater increase. Analyses of Fabp4, Mgmt , Fas, Nhej1, Aldh1a1 and Ncam1 were conducted via real-time quantitative polymerase chain reaction (RT-pPCR), using β-Actin as the control gene. There was an up-regulation of the Mgmt and Nhej1 gene transcripts in the exposed groups, with the extent of upregulation being highest in the HD group. Taken together, a link between environmental exposure to 2AA and pancreatic effects appears to exist.

Objectives: Studies suggest that impairments in some of the same domains of cognition occur in different neuropsychiatric conditions, including those known to share genetic liability. Yet, direct, multi-disorder cognitive comparisons are limited, and it remains unclear whether overlapping deficits are due to comorbidity. We aimed to extend the literature by examining cognition across different neuropsychiatric conditions and addressing comorbidity., Methods: Subjects were 486 youth consecutively referred for neuropsychiatric evaluation and enrolled in the Longitudinal Study of Genetic Influences on Cognition. First, we assessed general ability, reaction time variability (RTV), and aspects of executive functions (EFs) in youth with non-comorbid forms of attention-deficit/hyperactivity disorder (ADHD), mood disorders and autism spectrum disorder (ASD), as well as in youth with psychosis. Second, we determined the impact of comorbid ADHD on cognition in youth with ASD and mood disorders., Results: For EFs (working memory, inhibition, and shifting/ flexibility), we observed weaknesses in all diagnostic groups when participants' own ability was the referent. Decrements were subtle in relation to published normative data. For RTV, weaknesses emerged in youth with ADHD and mood disorders, but trend-level results could not rule out decrements in other conditions. Comorbidity with ADHD did not impact the pattern of weaknesses for youth with ASD or mood disorders but increased the magnitude of the decrement in those with mood disorders., Conclusions: Youth with ADHD, mood disorders, ASD, and psychosis show EF weaknesses that are not due to comorbidity. Whether such cognitive difficulties reflect genetic liability shared among these conditions requires further study. (JINS, 2018, 24, 91-103).

The blood-brain barrier (BBB) maintains brain homeostasis but also presents a major obstacle to brain drug delivery. Brain microvascular endothelial cells (BMECs) form the principal barrier and therefore represent the major cellular component of in vitro BBB models. Such models are often used for mechanistic studies of the BBB in health and disease and for drug screening. Recently, human induced pluripotent stem cells (iPSCs) have emerged as a new source for generating BMEC-like cells for use in in vitro human BBB studies. However, the inability to cryopreserve iPSC-BMECs has impeded implementation of this model by requiring a fresh differentiation to generate cells for each experiment. Cryopreservation of differentiated iPSC-BMECs would have a number of distinct advantages, including enabling production of larger scale lots, decreasing lead time to generate purified iPSC-BMEC cultures, and facilitating use of iPSC-BMECs in large-scale screening. In this study, we demonstrate that iPSC-BMECs can be successfully cryopreserved at multiple differentiation stages. Cryopreserved iPSC-BMECs retain high viability, express standard endothelial and BBB markers, and reach a high transendothelial electrical resistance (TEER) of ∼3000 Ω·cm 2 , equivalent to nonfrozen controls. Rho-associated coiled coil-containing kinase (ROCK) inhibitor Y-27632 substantially increased survival and attachment of cryopreserved iPSC-BMECs, as well as stabilized TEER above 800 Ω·cm 2 out to 7 days post-thaw. Overall, cryopreservation will ease handling and storage of high-quality iPSC-BMECs, reducing a key barrier to greater implementation of these cells in modeling the human BBB., Competing Interests: Statement No competing financial interests exist.

Cancer-targeting alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure-activity studies. While they strongly label human brain cancers associated with disrupted blood-brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm(2)) and functional expression of drug efflux transporters. The radioiodinated and fluorescent APC analogues demonstrated fairly low permeability across the iPSC-BMEC (35 ± 5.7 (CLR1404), 54 ± 3.2 (CLR1501), and 26 ± 4.9 (CLR1502) × 10(-5) cm/min) compared with BBB-impermeable sucrose (13 ± 2.5) and BBB-permeable diazepam (170 ± 29). Only the fluorescent APC analogues (CLR1501, CLR1502) underwent BCRP and MRP polarized drug efflux transport in the brain-to-blood direction of the BBB model, and this efflux can be specifically blocked with pharmacological inhibition. None of the tested APC analogues appeared to undergo substantial P-gp transport. Limited permeability of the APC analogues across an intact BBB into normal brain likely contributes to the high tumor to background ratios observed in initial human trials. Moreover, addition of fluorescent moieties to APCs resulted in greater BMEC efflux via MRP and BCRP, and may affect fluorescence-guided applications. Overall, the characterization of APC analogue permeability across human BBB is significant for advancing future brain tumor-targeted applications of these agents., Competing Interests: Jamey P. Weichert is the founder and shareholder in Cellectar Biosciences that provided the APC analogs used in this study. All other authors declare no competing financial interest.

The blood-brain barrier (BBB) is a critical component of the central nervous system (CNS) that regulates the flux of material between the blood and the brain. Because of its barrier properties, the BBB creates a bottleneck to CNS drug delivery. Human in vitro BBB models offer a potential tool to screen pharmaceutical libraries for CNS penetration as well as for BBB modulators in development and disease, yet primary and immortalized models respectively lack scalability and robust phenotypes. Recently, in vitro BBB models derived from human pluripotent stem cells (hPSCs) have helped overcome these challenges by providing a scalable and renewable source of human brain microvascular endothelial cells (BMECs). We have demonstrated that hPSC-derived BMECs exhibit robust structural and functional characteristics reminiscent of the in vivo BBB. Here, we provide a detailed description of the methods required to differentiate and functionally characterize hPSC-derived BMECs to facilitate their widespread use in downstream applications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with 'cross-disorder' relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability., Methods: Data are from 393 participants, ages 8-17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of the autism spectrum disorder, bipolar illness, and schizophrenia (including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively)., Results: We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits, but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting that it related to a general increase in psychopathology symptoms across those dimensions., Conclusions: Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relates to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability., (© 2015 Association for Child and Adolescent Mental Health.)

Background: Brain microvascular-like endothelial cells (BMECs) derived from human pluripotent stem cells (hPSCs) have significant promise as tools for drug screening and studying the structure and function of the BBB in health and disease. The density of hPSCs is a key factor in regulating cell fate and yield during differentiation. Prior reports of hPSC differentiation to BMECs have seeded hPSCs in aggregates, leading to non-uniform cell densities that may result in differentiation heterogeneity. Here we report a singularized-cell seeding approach compatible with hPSC-derived BMEC differentiation protocols and evaluate the effects of initial hPSC seeding density on the subsequent differentiation, yield, and blood-brain barrier (BBB) phenotype., Methods: A range of densities of hPSCs was seeded and differentiated, with the resultant endothelial cell yield quantified via VE-cadherin flow cytometry. Barrier phenotype of purified hPSC-derived BMECs was measured via transendothelial electrical resistance (TEER), and purification protocols were subsequently optimized to maximize TEER. Expression of characteristic vascular markers, tight junction proteins, and transporters was confirmed by immunocytochemistry and quantified by flow cytometry. P-glycoprotein and MRP-family transporter activity was assessed by intracellular accumulation assay., Results: The initial hPSC seeding density of approximately 30,000 cells/cm(2) served to maximize the yield of VE-cadherin+ BMECs per input hPSC. BMECs displayed the highest TEER (>2,000 Ω × cm(2)) within this same range of initial seeding densities, although optimization of the BMEC purification method could minimize the seeding density dependence for some lines. Localization and expression levels of tight junction proteins as well as efflux transporter activity were largely independent of hPSC seeding density. Finally, the utility of the singularized-cell seeding approach was demonstrated by scaling the differentiation and purification process down from 6-well to 96-well culture without impacting BBB phenotype., Conclusions: Given the yield and barrier dependence on initial seeding density, the singularized-cell seeding approach reported here should enhance the reproducibility and scalability of hPSC-derived BBB models, particularly for the application to new pluripotent stem cell lines.

Context: Recent data suggest that severe stress during the adolescent period is becoming a problem of epidemic proportions. Elicitation of the relaxation response (RR) has been shown to be effective in treating anxiety, reducing stress, and increasing positive health behaviors., Objective: The research team's objective was to assess the impact of an RR-based curriculum, led by teachers, on the psychological status and health management behaviors of high-school students and to determine whether a train-the-trainer model would be feasible in a high-school setting., Design: The research team designed a pilot study., Setting: The setting was a Horace Mann charter school within Boston's public school system., Participants: Participants were teachers and students at the charter school., Intervention: The team taught teachers a curriculum that included (1) relaxation strategies, such as breathing and imagery; (2) psychoeducation regarding mind-body pathways; and (3) positive psychology. Teachers implemented this curriculum with students., Outcome Measures: The research team assessed changes in student outcomes (eg, stress, anxiety, and stress management behaviors) using preintervention/postintervention surveys, including the Perceived Stress Scale (PSS), the State-Trait Anxiety Inventory-Form Y (STAI-Y), the stress management subscale of the Health-promoting Lifestyle Profile II (HPLP-II), the Rosenberg Self-Esteem Scale (RSES), the Locus of Control (LOC) questionnaire, and the Life Orientation Test-Revised (LOTR). Classroom observations using the Classroom Assessment Scoring System (CLASS)-Secondary were also completed to assess changes in classroom environment., Results: Using a Bonferroni correction (P < .007), the study found that students experienced a significant reduction (P < .001) in measures of state-level anxiety on the STAI from pre- to postintervention. The study also found an increase in the use of stress management behaviors at that point. Using a Bonferroni correction (P < .007), the study found that students had significantly less perceived stress (P < .001), less state anxiety (P < .001) and trait anxiety (P < . 001), and increased use of positive stress management behaviors (P < .004) at the follow-up assessment in the fall of the following year. Using a Bonferroni correction (P < .002), the study found a significant increase in overall classroom productivity (eg, increased time spent on activities and instruction from pre- to postintervention)., Conclusions: This study showed that teachers can lead an RR curriculum with fidelity and suggests that such a curriculum has positive benefits on student emotional and behavioral health and on classroom functioning.

Accumulating evidence suggests that endothelial cells (ECs) display significant heterogeneity across tissue types, playing an important role in tissue regeneration and homeostasis. Recent work demonstrating the derivation of tissue-specific microvascular endothelial cells (TS-MVECs) from human pluripotent stem cells (hPSCs) has ignited the potential to generate tissue-specific models which may be applied to regenerative medicine and in vitro modeling applications. Here, we review techniques by which hPSC-derived TS-MVECs have been made to date and discuss how current hPSC-EC differentiation protocols may be directed toward tissue-specific fates. We begin by discussing the nature of EC tissue specificity in vivo and review general hPSC-EC differentiation protocols generated over the last decade. Finally, we describe how specificity can be integrated into hPSC-EC protocols to generate hPSC-derived TS-MVECs in vitro, including EC and parenchymal cell coculture, directed differentiation, and direct reprogramming strategies., (© 2014 AlphaMed Press.)

The blood-brain barrier (BBB) is crucial to the health of the brain and is often compromised in neurological disease. Moreover, because of its barrier properties, this endothelial interface restricts uptake of neurotherapeutics. Thus, a renewable source of human BBB endothelium could spur brain research and pharmaceutical development. Here we show that endothelial cells derived from human pluripotent stem cells (hPSCs) acquire BBB properties when co-differentiated with neural cells that provide relevant cues, including those involved in Wnt/β-catenin signaling. The resulting endothelial cells have many BBB attributes, including well-organized tight junctions, appropriate expression of nutrient transporters and polarized efflux transporter activity. Notably, they respond to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance (1,450 ± 140 Ω cm2), and they possess molecular permeability that correlates well with in vivo rodent blood-brain transfer coefficients.

This study examined whether adolescent females with attention-deficit/hyperactivity disorder (ADHD) are differentially responsive than their male counterparts to extended-release stimulant medications. This investigation may bear special importance for an adolescent (as opposed to child) population, because hormonal and metabolism differences between sexes are most likely to emerge at this time. Male (n = 19) and female (n = 16) adolescents, ages 16-19 with ADHD, participated in a randomized, double-blind crossover study evaluating the effectiveness of osmotic-release methylphenidate, extended release amphetamine salts, placebo, and routine limited medication regimen. Medication efficacy was evaluated using ADHD symptom ratings from adolescent self-report and parent report, along with objective measures of inattention and hyperactivity/impulsivity during driving performance and neuropsychological tasks. Males and females were largely equivalent in impairment, and medication was similarly effective in reducing symptoms. No interactions were found between sex and medication on any measure of effectiveness or side effects. This finding suggests that the efficacy and tolerability of extended-release stimulant medications is equivalent for male and female adolescents with ADHD.

Oxidative stress may be an important determinant of the severity of acute pancreatitis. One-electron reduction of oxidants generates reactive oxygen species (ROS) via redox cycling, whereas two-electron detoxification, e.g. by NAD(P)H:quinone oxidoreductase, does not. The actions of menadione on ROS production and cell fate were compared with those of a non-cycling analogue (2,4-dimethoxy-2-methylnaphthalene (DMN)) using real-time confocal microscopy of isolated perfused murine pancreatic acinar cells. Menadione generated ROS with a concomitant decrease of NAD(P)H, consistent with redox cycling. The elevation of ROS was prevented by the antioxidant N-acetyl-l-cysteine but not by the NADPH oxidase inhibitor diphenyliodonium. DMN produced no change in reactive oxygen species per se but significantly potentiated menadione-induced effects, probably via enhancement of one-electron reduction, since DMN was found to inhibit NAD(P)H:quinone oxidoreductase detoxification. Menadione caused apoptosis of pancreatic acinar cells that was significantly potentiated by DMN, whereas DMN alone had no effect. Furthermore, bile acid (taurolithocholic acid 3-sulfate)-induced caspase activation was also greatly increased by DMN, whereas DMN had no effect per se. These results suggest that acute generation of ROS by menadione occurs via redox cycling, the net effect of which is induction of apoptotic pancreatic acinar cell death. Two-electron detoxifying enzymes such as NAD(P)H:quinone oxidoreductase, which are elevated in pancreatitis, may provide protection against excessive ROS and exert an important role in determining acinar cell fate.

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with diminished neuropsychological functioning. This randomized, double-blind, placebo controlled, study is the first comparison of two extended release stimulant-based medications (Adderall XR and Concerta) and placebo on ADHD neuropsychological functioning. Adolescents diagnosed with ADHD (n=35, 19 males) completed three separate assessments (5, 8, 11 p.m.) on three different days and medications (Concerta, Adderall XR and Placebo). The assessments consisted of two different neuropsychological tests, the Delayed Matching-to-Sample and the Go/No-go (GNG), which measure visual memory, attention span, and response inhibition. Results indicated a significant effect of medication on signs of impulsivity and memory. Simple contrasts showed significant improvement in neuropsychological functioning (as measured by commission errors, reaction time, and recall accuracy) when participants were taking Concerta as opposed to placebo. These results suggest that Concerta impacts not only symptomatic behaviors but also cognitive functioning, which has implications for both academic performance and daily functioning.

The 2f1-f2 distortion product otoacoustic emission (DPOAE) is considered to consist of two components in normally hearing ears, one having constant phase with changing DP frequency (wave fixed) and one having an increasing phase lag with increasing frequency (place fixed). The aim was to identify the wave-fixed and place-fixed components of both 2f1-f2 and 2f2-f1 DPs, and, in particular, to show whether a wave-fixed 2f2-f1 DP exists in normally hearing adults. DPOAE recordings were made in 20 ears of normally hearing young adults. Four frequency ratios were used and recording entailed fixed frequency-ratio sweeps. A separation into wave-fixed and place-fixed components was carried out using a time-window separation method. A method for estimating the noise floor after data processing was developed. Results confirmed the presence of wave-fixed and place-fixed components for 2f1-f2, consistent with previous studies. Both components were also present for 2f2-f1 in virtually all subjects. This latter finding conflicts with current models of DPOAE generation, and so a modified model is proposed. Unlike the 2f1-f2 emission, which has a wave-fixed component that is strongly dependent on the frequency ratio, neither component of the 2f2-f1 emission showed such a dependence. The proposed model explains these findings in terms of the overlap of the primary frequency traveling waves.

The 2F1-F2 distortion product otoacoustic emission (DPOAE) is considered to consist of two generation mechanisms, the so-called place-fixed and wave-fixed mechanisms, depending on the frequency ratio F2/F1. The general assumption is that for a small frequency ratio there is a predominantly place-fixed emission mechanism, while with a larger frequency ratio there is a predominantly wave-fixed mechanism. There is also a lack of published data on the repeatability of the two components when separated. One aim of this study was therefore to identify the wave-fixed and place-fixed components of the 2F1-F2 DPOAE using a time-window separation method. The second aim was to quantify the test-retest repeatability of the separated 2F1-F2 DPOAE components in a group of normally hearing subjects. Results confirmed the presence of wave-fixed and place-fixed components for 2F1-F2 and a predominance of place or wave-fixed DPOAE as a function of frequency ratio. This pattern varied somewhat among subjects. Moreover, regardless of which component was stronger for any F2/F1, both components were highly repeatable across time within individual ears.

The effect of surgery for femoral neck fracture on lower limb venous blood flow and its relationship to deep vein thrombosis was investigated in 179 patients. Blood flow was measured using strain gauge plethysmography before surgery, in the 1st week after surgery, and at 6 week review. There was a significant reduction in both venous outflow and venous capacitance, affecting both fractured and non-fractured legs but significantly greater in the fractured leg. Venous function remained significantly impaired in both lower limbs 6 weeks after surgery. There was a significant correlation between the reduction in venous function and the development of deep vein thrombosis.

The effect of surgery for femoral neck fracture on whole blood coagulation and the relationship of altered coagulation to deep venous thrombosis were investigated in 250 patients. Whole blood coagulation was measured using thrombelastography preoperatively, in the early postoperative period and at 6-week review. Significant hypercoagulability was demonstrated after surgery and persisted to 6-week review. A significant correlation between hypercoagulability and the development of deep venous thrombosis is demonstrated. Hypercoagulability is shown to be a major factor in thrombosis formation following proximal femoral neck fracture surgery.

Breath analysis is an attractive non-invasive procedure for screening workers exposed to solvents. It has been used in numerous laboratory based studies and for field research. Despite the obvious advantages in routine biological monitoring it has failed to become widely accepted as a tool in occupational hygiene. Recent advances in breath sampling and analysis are such that it is likely to become more widely used in the future. In this paper, the past 5 years have been reviewed to try to assess what developments might now contribute to the increased use of breath analysis in biological monitoring; in particular, the development of a selected ion flow tube mass spectrometer for real time direct analysis of trace gases in breath and the more immediately available and less expensive indirect methods involving collection devices with adsorbent tubes is important. The introduction of guidance values for biological monitoring with clear advice on sampling times and the recognition of the importance of quality assurance programmes will help improve confidence in the technique.

Policy developments in the United Kingdom have been aimed at facilitating the appropriate use of biological monitoring. Recent initiatives have established clear criteria for the interpretation of biological monitoring results, and new guidance that deals with the ethical and practical issues involved in operating an effective biological monitoring programme has been promulgated. The United Kingdom now has a system of non-statutory biological monitoring guidance values. There are two types, the health guidance value and the benchmark guidance value. Over a number of years, biological monitoring programmes have shown that they help in reducing exposure by regular monitoring and demonstrating adequate control.

1-Methoxy-2-propanol (M2P) is finding increasing industrial use as a less toxic alternative to the short-chained ethylene glycol ethers. Like most glycol ethers, M2P is readily absorbed through the skin and biological monitoring is therefore appropriate in assessing occupational exposure. An analytical method, suitable for routine monitoring, was developed for the determination of free M2P in urine. The method involves solvent extraction, gas chromatography-mass spectrometry and is sensitive (detection limit 1 mumol/l), specific and reproducible (intra- and inter-assay coefficients of variation 5% and 9%, respectively). A human volunteer study, involving six volunteers, was also conducted. Volunteers were exposed to 100 ppm M2P for 8 h (the occupational exposure standard in the UK) including a 30-min break. Post-exposure levels of free M2P in urine were found to reach up to 110 mumol/l). Levels of M2P were also monitored in blood (maximum 103 mumol/l) and exhaled air samples (up to 252 nmol/l). The volunteer study showed that M2P is rapidly excreted in urine with a half-life of less than 2.6 h.

We have developed a novel breath sampling device suitable for capturing a portion of end-tidal air. This breath sample is then transferred onto a Perkin Elmer automated thermal desorption (ATD) sampling tube which is subsequently analysed by ATD-gas chromatography-mass spectrometry (GCMS). The breath sampler has been evaluated in the laboratory, in brief field trials and in human volunteer studies. The method is sensitive with a typical detection limit of 1 nmol/l and reproducible with an overall coefficient of variation between 5% and 15% for collection and analysis of breath samples from volunteers. The field trials used the sampler to assess exposure to solvents in several industries including the shoe manufacturing industry, the inks and coatings industry and at dry cleaning establishments. The sampler was found easy to use and reliable. Solvents detected include ethyl acetate (6.4-25.5 nmol/l), propan-2-ol (3.4-39.3 nmol/l), 2-butanone (0-6.6 nmol/l) and tetrachloroethene (0-557 nmol/l). The breath sampler was also used to monitor the elimination of solvents in breath from human volunteers after exposure chamber studies. More than 500 breath samples have been analysed from 24 volunteers in exposures to 10 different solvents (toluene, trimethyl benzene, tetrachloroethene, tetrahydrofuran, acetone, propan-2-ol, xylene, 2-butanone, 1-methoxy-2-propanol and n-hexane). The breath sampler allowed the rapid and non-invasive collection of data on elimination of solvents.

In 1996 the United Kingdom's Health and Safety Executive introduced biological monitoring guidance values for six substances, butoxyethanol, N,N-dimethylacetamide, lindane, methylene-bis(2-chloroaniline), mercury and methylenedianiline. These guidance values were set as either health-based values or hygiene-based values calculate according to the 90th percentile (benchmark concept). Recent technical developments from the Health and Safety Laboratory are described in this paper and include: (i) the use of breath analysis as a useful non-invasive routine monitoring technique; (ii) flow cytometry as a means for measuring different patterns of immune cell activation from workers exposed to respiratory sensitisers when compared with those exposed to chemical irritants; (iii) the use of molecular techniques to explore the possible role of individual susceptibility in the development and severity of glomerulonephritis; (iv) the development of expert systems for predicting the skin permeability of chemicals, and respiratory and skin sensitisation.

A cross-sectional study of 34 workers engaged in thermal spraying at six worksites was undertaken in order to determine levels of exposure to and uptake of metals during different metal spraying activities. Levels of exposure to cobalt, chromium and nickel were highest in plasma sprayers and, on occasions exceeded UK Occupational Exposure Limits. Exposure to metals during detonation gun and electric arc spraying was better controlled and levels remained below the relevant Occupational Exposure Limits throughout the study period. Urinary levels of cobalt and nickel mirrored the airborne concentrations and the highest urine concentrations were again found in plasma sprayers. Urinary chromium levels were highest in electric arc sprayers, which may also reflect an increased body burden in this group due to a longer history of exposure. The findings clearly indicate that exposure to and uptake of metals may exceed UK Occupational Limits or Standards when spraying is performed manually or semi-automatically and where control relies on local exhaust ventilation (LEV) and personal respiratory protective equipment (RPE).

A sensitive and rapid technique for directly measuring silver in blood, using electrothermal atomization atomic absorption spectrophotometry (ETAAS) is described. The method can be used to analyse precisely up to 40 blood samples a day in duplicate. Well-mixed, whole blood samples, collected in EDTA, were diluted 1 + 4 with a diluent containing 40 g l.-1 ammonium dihydrogen orthophosphate and 0.5 ml l.-1 Triton X-100. Aliquots of diluted blood were then analysed by ETAAS using wall atomization with a pyrolytically coated tube. The coefficient of variation for within-run precision was 4.55% at 10 micrograms 1.-1 and 5% at 25 micrograms 1.-1 Between-run variation, it was 4.1% at 25 micrograms l.-1 The analytical recovery for the method was 98% +/- 3% at both 8 and 30 micrograms 1. -1 The detection limit of the method was 0.1 microgram 1. -1, which was sufficiently sensitive to distinguish exposed from non-exposed individuals. Blood silver levels in unexposed subjects were found to be between < 0.1 and 0.2 micrograms 1. -1. Blood silver levels were determined in 98 occupationally exposed workers involved in bullion production, cutlery manufacture, chemical manufacture, jewelery production and silver reclamation. Blood silver levels ranged from 0.1 to 23 micrograms 1.-1, with some of the highest levels found in silver reclaimers.

Abstract We report the development and validation of a high performance liquid chromatography method for the determination of methylene bis (2-chloroaniline) (MbOCA) and its labile conjugates in urine. The method has been in regular use for the biological monitoring of workers exposed to MbOCA for the past 11 years. Following the development of a biological monitoring strategy, and the introduction of a biological action level by the Health and Safety Commission in 1984, there has been a steady fall in the proportion of workers whose urinary results are above the action level. We conclude that, in the absence of reliable health-based data, a guidance value based on the use of the 90th percentile derived from monitoring a cross-section of the industry, can be used to interpret biological monitoring results. The measurement of urinary MbOCA is a practical non-invasive way of monitoring workers which can be useful in helping to control exposure.

A 38-year-old physician presented with a 9-month history of progressive self-administration of oral prednisone < or = 160 mg per day for Addison's disease. Examination demonstrated typical Cushingoid features and bilateral proptosis with elevated intraocular pressure. Computed tomography disclosed increased intraorbital adipose tissue. We hypothesize that the increased intraorbital adipose deposition was due to the differential binding of glucocorticoids to adipose tissue receptors and an enhancement of lipoprotein lipase activity. We conclude that the findings in this case may be related to glucocorticoid-induced changes in the ocular and periorbital structures. Cushing's syndrome should be considered in the differential diagnosis of acquired exophthalmos and elevated intraocular pressure and findings of increased orbital fat on orbital imaging.

This paper describes a cross sectional study in which biological monitoring was used to assess exposure to methylene dianiline (MDA) in a selection of United Kingdom industries that manufacture or use MDA. Samples of urine were collected from 411 workers, representing 45 factories engaged in various activities. All urine samples were analysed for MDA and its acetyl metabolites and results are reported as total MDA. In this study, 91% of postshift urine samples and 88% of preshift samples had less than 50 nmol MDA/mmol creatinine. Some evidence was obtained which showed that when exposure to MDA was through inhalation (as solid material or contaminated dust), postshift urine samples had higher MDA concentrations than samples taken preshift the next day. When exposure was most likely to be through the dermal route, urine samples taken preshift next day tended to have higher MDA concentrations than urine samples collected immediately postshift on the day of exposure. Therefore a biological monitoring sampling strategy for MDA must take account of the route of entry into the body. If exposure is likely to be via inhalation, postshift samples should be collected and if exposure is likely via the skin, preshift samples next day are more appropriate. The results show that in most factories, regardless of the route of exposure, it is possible to keep urinary MDA concentrations below 50 nmol/mmol creatinine. In the absence of a health based or hygiene based standard, the use of a "yardstick" as a target to aim for, which has been derived from good working practice across the industry, may be a useful way of helping to control exposure.

The in vitro rates of aging and spontaneous reactivation of human plasma cholinesterase (ChE) after inhibition by several organophosphorus pesticides (OPs) have been studied. After inhibition by OP the enzyme can undergo two simultaneous reactions; spontaneous reactivation to the active enzyme and 'aging' to an irreversibly inhibited form of the enzyme. The rates of these two reactions depend on the nature of the phosphoryl group of the OP bound to the active site of ChE. Most OPs registered for use in the UK have dimethoxy or diethoxy groups attached to the phosphorus atom. Reaction rate constants for aging and spontaneous reaction are reported. Dimethoxy OPs cause half-lives of aging in human plasma ChE of approximately 6 hours and 23 hours at 37 degrees C and 22 degrees C respectively; for diethoxy OPs the values are 12 hours and 39 hours. Reappearance of enzyme activity, after removal of OP, reduced any inhibition by a maximum of 25% for dimethoxy OPs; this reappearance of enzyme activity occurs with a 'half-life' of 5 hours and 15 hours at 37 degrees C and 22 degrees C. These effects, both in vivo and ex vivo, may have relevance in developing a monitoring strategy for dimethoxy OPs using plasma ChE measurements. Inhibition by diethoxy OPs spontaneously reactivates very slowly, even at 37 degrees C, and would not practically influence the measured inhibition. No spontaneous reactivation was detected in human plasma ChE inhibited by the methoxy-ethylamino substituted OP (propetamphos) or the methoxy-methylamino substituted OP (crufomate) during 45 hours incubation at 37 degrees C.

The determination of arsenite, arsenate, dimethylarsenic acid (DMA) and monomethylarsonic acid (MMA) in urine has been used for assessing occupational exposure to inorganic arsenic because these species were thought to be unaffected by dietary arsenic. However, this investigation reports how the consumption of certain types of seafood can lead to an increase in the amount of DMA excreted and hence an elevation in the urinary arsenic speciation total. Urine samples collected from volunteers between 4-20 hours after the ingestion of moderate-sized portions of mackerel, herring, crab or tuna, showed mean increases in the arsenic speciation totals of between 1.8 and 6.9 times compared with the levels in samples collected before the seafood was consumed. These findings have important implications in devising a biological monitoring strategy for workers exposed to inorganic arsenic.

We have examined the potential use of salivary cadmium measurements for the biological monitoring of occupational cadmium exposure, paying particular attention to the contamination risks associated with such measurements. We have developed a method for the direct determination of cadmium in saliva by graphite furnace atomic absorption spectrophotometry, which minimizes the risk of contamination during sample preparation and analysis. The limit of detection is 0.6 nmoll-1, which is sufficiently sensitive to discriminate between unexposed and occupationally exposed individuals. The method has been employed to measure cadmium levels in saliva samples collected by two different methods from an unexposed population, a group of ex-workers previously exposed to cadmium (Group 1), and two groups of currently exposed workers (Groups 2 and 3). Salivary cadmium levels were significantly raised in both of the groups of currently exposed individuals (group 2 median (Md) = 17 nmoll-1, group 3 Md = 70 nmoll-1, p greater than 0.0001), and in past workers with previous long-term exposure (Group 1 Md = 2.5 nmoll-1, p greater than 0.001) when compared with an unexposed population. The results suggest that the measurement of salivary cadmium may reflect recent exposure to the metal. However, considerable care must be taken in collecting samples because a risk of contamination during sampling is apparent with procedures commonly used for saliva collection, and for this reason the applicability of such measurements for biological monitoring is limited.

Experimental work has been undertaken to investigate the potential interference of toluene, 1,1,1-trichloroethane and butane with the evidential breath alcohol testing instruments used in Great Britain (Lion Intoximeter 3000 and Camic Breath Analyser). Volunteers inhaled the volatile substances in an exposure chamber for up to 4 hours, at concentrations of 100, 350 and 600ppm respectively. Subsequently breath was tested on leaving the chamber. No interference was observed with the breath alcohol instruments when the subjects were exposed to toluene and 1,1,1-trichloroethane. A short-term response immediately after exposure was observed for subjects exposed to butane. Further analytical work involving blood and breath samples demonstrated that all three volatile substances were absorbed during exposure and were detectable in blood for at least 3 hours post-exposure. Their elimination post-exposure followed an exponential decay.