Canonical and non-canonical integrin-based adhesions dynamically interconvert.

Adhesions are critical for anchoring cells in their environment, as signaling platforms and for cell migration. In line with these diverse functions different types of cell-matrix adhesions have been described. Best-studied are the canonical integrin-based focal adhesions. In addition, non-canonical integrin adhesions lacking focal adhesion proteins have been discovered. These include reticular adhesions also known as clathrin plaques or flat clathrin lattices, that are enriched in clathrin and other endocytic proteins, as well as extensive adhesion networks and retraction fibers. How these different adhesion types that share a common integrin backbone are related and whether they can interconvert is unknown. Here, we identify the protein stonin1 as a marker for non-canonical αVß5 integrin-based adhesions and demonstrate by live cell imaging that canonical and non-canonical adhesions can reciprocally interconvert by the selective exchange of components on a stable αVß5 integrin scaffold. Hence, non-canonical adhesions can serve as points of origin for the generation of canonical focal adhesions.

Longitudinal examination of alcohol use motives, item-level protective behavioral strategies, and alcohol-related consequences.

BACKGROUND: Alcohol misuse among college students is a public health concern. Protective behavioral strategies (PBS) can be used before, during, after, or instead of drinking to reduce alcohol use and negative consequences, but findings on their utility at the aggregate level are mixed. Although recent work has provided important information on the performance of individual PBS items, it is limited by research designs that are cross-sectional, do not examine consequences, or do not examine other important correlates, such as drinking motives. This study examines both the association between item-level PBS and alcohol-related negative consequences and the moderating effect of drinking motives longitudinally. METHODS: College students from two universities (n = 200, 62.5% female, Mage = 20.16) completed the Drinking Motives Questionnaire-Revised, Protective Behavioral Strategies Survey, the Rutgers Alcohol Problem Index, and a measure of the quantity of alcohol use at baseline and 3-month follow-up. Generalized linear models were conducted to assess direct effects of item-level PBS on alcohol-related consequences and the moderating effects of drinking motives. RESULTS: Two PBS items were associated with fewer alcohol-related consequences at follow-up, and two items were associated with greater alcohol-related consequences at follow-up. Drinking motives differentially moderated associations between item-level PBS and alcohol-related consequences for a proportion in the sample. Enhancement motives moderated the greatest number of associations, followed by coping, conformity, and social motives. Certain PBS (e.g., drink slowly, rather than gulp or chug) were moderated by several drinking motives, whereas other PBS items were not moderated by any motives. CONCLUSION: Consistent with previous research, some item-level PBS were associated longitudinally with increased negative consequences, and some were associated with decreased negative consequences. Drinking motives, particularly enhancement, moderated several item-level PBS and consequence associations, suggesting that reasons for drinking may be important for understanding the associations between PBS strategies and alcohol-related consequences.

Whose Approval Matters Most? Examining Discrepancies in Self- and Other- Perceptions of Drinking.

BACKGROUND: Research demonstrates that perceptions of others' attitudes toward drinking behaviors (injunctive norms) are strong predictors of alcohol consumption and problems. Personalized normative feedback (PNF) aims to reduce the discrepancy between one's perception of others' attitudes toward drinking and others' actual attitudes toward drinking. An implicit assumption of PNF is that self and (perceived) other attitudes toward drinking are aligned (thus, shifting one's perceptions of others' attitudes shifts one's own attitudes). However, there is minimal research on the extent to which alignment (or discrepancy) in self-other attitudes toward drinking is associated with alcohol-related outcomes. METHODS: College students (N = 1,494; Mage = 20.11, 61.0% female, 66.4% White) who endorsed past-month heavy episodic drinking reported injunctive norms toward drinking on weekends, drinking daily, drinking to black out, and drinking and driving. Participants reported their perceptions of attitudes toward these drinking behaviors for three reference groups: close friends, typical university-affiliated peers, and parents. Outcomes included weekly drinking, alcohol problems, and alcohol-related risk. RESULTS: Response surface analyses indicated that alignment in approval (versus alignment in disapproval) of drinking demonstrated a linear association with alcohol-related outcomes. Discrepancies in self-peer and self-parent attitudes were associated with alcohol-related outcomes and one's own attitudes (versus one's ratings of others' attitudes) of drinking were more strongly associated with outcomes. CONCLUSIONS: Results provide evidence of how self-other discrepancies in attitudes toward drinking are associated with alcohol-related outcomes. Future work is needed to test whether self-other discrepancies in attitudes toward drinking impacts response to norms-based interventions.

Why get high? Coping and enjoyment motives mediate elevated cannabis demand and cannabis-related outcomes.

OBJECTIVE: Cannabis is the most used psychoactive substance among adolescents and is a public health concern. Cannabis demand is a quantifiable measure of the reinforcing value of cannabis and comprises two latent-factors-amplitude (maximum consumption) and persistence (sensitivity to increasing costs). Cannabis demand and cannabis motives are important predictors of adolescent cannabis use and associated problems; however, little is known about how these two facets of motivation are causally related. Cannabis motives are thought to represent the final common pathway to cannabis use and may explain why elevated demand is associated with use and consequences. The present study tested whether internal cannabis motives (coping and enjoyment) mediated longitudinal associations between cannabis demand, use (hours high), and negative consequences. METHOD: Participants aged 15-18 years old (n = 89, Mage = 17.0, SD = 0.9) who reported lifetime cannabis use completed online assessments of cannabis demand, motives, use and negative consequences at baseline, 3-month, and 6-month follow-up. RESULTS: PROCESS mediation models revealed that enjoyment motives mediated the association between amplitude and persistence and use. In addition, coping motives mediated the association between amplitude and negative consequences. CONCLUSIONS: These findings suggest that internal motives, while differentially related to aspects of demand and cannabis outcomes, are important in understanding adolescent cannabis use. Prevention efforts aimed at limiting access to cannabis and increasing access to substance-free activities may be important targets for adolescents. Further, cannabis interventions targeting specific motives for using (e.g., to cope with negative affect) may be important for reducing cannabis demand. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Alcohol and marijuana use predicting next-day absenteeism and engagement at school and work: A daily study of young adults.

This study examined effects of alcohol and marijuana use on next-day absenteeism and engagement at work and school among young adults (18-25 years old) who reported past-month alcohol use and simultaneous alcohol and marijuana use. Participants completed twice daily surveys for five, 14-day bursts. The analytic sample was 409 [64 % were enrolled in university (N = 263) and 95 % were employed (N = 387) in at least one burst]. Daily measures included: any alcohol or marijuana use, quantity of alcohol or marijuana use (i.e., number of drinks, number of hours high), attendance at work or school, and engagement (i.e., attentiveness, productivity) at school or work. Multilevel models examined between- and within-person associations between alcohol and marijuana use and next-day absenteeism and engagement at school or work. Between-persons, the proportion of days of alcohol use days was positively associated with next-day absence from school, consuming more drinks was positively associated with next-day absence from work, and the proportion of days of marijuana use was positively associated with next-day engagement at work. At the daily-level, when individuals consumed any alcohol and when they consumed more drinks than average, they reported lower next-day engagement during school and work. When individuals used marijuana and when they were high for more hours than average, they reported lower next-day engagement during school. Findings suggest alcohol and marijuana use consequences include next-day absence and decrements in next-day engagement at school and work, which could be included in interventions aimed at ameliorating harmful impacts of substance use among young adults.

Can I see some ID? Examining validity of the marijuana purchase task among late adolescent cannabis users.

Cannabis demand (i.e., reinforcing value) can be assessed using a marijuana purchase task (MPT; assesses hypothetical purchasing of cannabis at escalating prices) and has been related to use frequency, problems, and cannabis use disorder symptoms in adults. Cannabis demand has yet to be studied in adolescents, which can inform prevention and intervention efforts to reduce cannabis-related risks. The present study sought to validate the MPT with a sample of late adolescent lifetime cannabis users. Participants aged 15-18 years old (n = 115, Mage = 16.9, SD = 0.9) residing in a state with legalized cannabis use completed online assessments at baseline and 6-month follow-up. Convergent and divergent validity was examined, while principal component analysis was conducted to determine the factor structure and assess predictive validity. Three indices, Omax (i.e., maximum expenditure on cannabis), breakpoint (i.e., price suppressing consumption to zero), and alpha (i.e., degree to which consumption decreases with increasing price) were all significantly associated with cannabis use, consequences, craving, and expenditures and significantly differentiated low-risk users and high-risk users as measured by the Cannabis Use Disorders Identification Test-Revised (CUDIT-R). A two-factor solution reflecting amplitude (intensity, alpha, Omax) and persistence (breakpoint, Pmax) was observed. Both factors were associated with cannabis use and consequences in baseline regression models. At follow-up, persistence was associated with consequences; amplitude was not associated with either outcome. These findings provide initial evidence that the MPT is a valid measure for assessing cannabis demand among adolescents and can be used to understand mechanisms of adolescent cannabis use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Repeated Assessment of Alcohol Use and Perceived Norms Among College Students Who Drink: Comparisons to a Minimal Assessment at 12-Month Follow-Up.

OBJECTIVE: Clinical trials assessing efficacy of alcohol use interventions often aim to test differences between treatment and control conditions at several follow-up time points, requiring repeated assessment of outcomes (e.g., weekly number of drinks). There has been concern that repeated assessment may elicit assessment reactivity in which participants, even those who did not receive treatment, reduce their alcohol use, but findings in the literature have been mixed. The current study of assessment reactivity compared two control conditions that were part of a larger randomized controlled trial: (a) repeated assessment that completed surveys at baseline, 3-, 6-, and 12-month follow-ups, and (b) minimal assessment that only completed surveys at baseline and 12-month follow-up. Outcomes assessed at 12-month follow-up included (a) changes in alcohol use behavior and negative consequences, (b) changes in perceived descriptive and injunctive norms, and (c) participant attrition/retention. METHOD: Participants were undergraduate students who reported at least one heavy drinking occasion (4+/5+ drinks for women/men) in the past month (N = 456; 63.3% female; mean age = 20.11 years). RESULTS: Multiple regression models indicated no significant differences between the repeated and minimal assessment control conditions on any indices of alcohol use (p values ranged from .42 to .97), negative consequences (p = .39), or on perceived descriptive/injunctive norms (p = .60 and .23, respectively). Attrition at 12-month follow-up was low in both groups, but significantly higher (p = .006) in the repeated assessment condition (16.49%) than the minimal assessment condition (8.55%). CONCLUSIONS: Repeated assessment did not elicit changes in alcohol use, negative consequences, or perceived norms. A minimal assessment control condition may not be necessary when assessing intervention efficacy across longitudinal follow-ups. However, when attrition at 12-month follow-up is a salient concern, a minimal assessment control may retain more participants than repeated assessment.

Simultaneous Alcohol and Marijuana Use Among Young Adults: A Scoping Review of Prevalence, Patterns, Psychosocial Correlates, and Consequences.

BACKGROUND: Alcohol and marijuana are commonly used by young adults, and use of both substances, particularly at the same time, is prevalent among this population. Understanding the prevalence, patterns, correlates, and consequences of simultaneous alcohol and marijuana (SAM) use is important to inform interventions. However, this literature is complicated by myriad terms used to describe SAM use, including use with overlapping effects and same-day co-use. OBJECTIVES: This scoping review identifies and describes the peer-reviewed literature focused on SAM use by young adults and distinguishes simultaneous use from same-day co-use of alcohol and marijuana. This review also provides a narrative summary of the prevalence of SAM use, patterns of SAM and other substance use, psychosocial correlates, and consequences of SAM use. ELIGIBILITY CRITERIA: This review is limited to papers written in English and published in peer-reviewed journals between January 2000 and August 2021. It includes papers assessing simultaneous use or same-day co-use of alcohol and marijuana among young adults ages 18 to 30. Review papers, qualitative interviews, experimental lab studies, policy work, toxicology or medical reports, and papers focused on neurological outcomes are excluded. SOURCES OF EVIDENCE: PubMed, PsycINFO, and Web of Science databases were searched. Databases were selected and the search strategy developed in consultation with an information specialist. CHARTING METHODS: A data charting form was utilized to specify which information would be extracted from included papers. Eight categories of data were extracted: (1) research questions and hypotheses; (2) sample characteristics; (3) study procedures; (4) definition of SAM use; (5) prevalence of SAM use; (6) patterns of SAM and other substance use; (7) psychosocial correlates of SAM use; and (8) consequences of SAM use. RESULTS: A total of 1,282 papers were identified through initial search terms. Through double-blind title/abstract screening and full-text review, the review was narrowed to 74 papers that met review inclusion criteria. Review of these papers demonstrated that SAM use was prevalent among young adults, particularly among those who reported heavier quantities and more frequent use of alcohol and marijuana. Enhancement-related motives for use were consistently positively associated with SAM use. SAM use was associated with greater perceived positive and negative consequences of alcohol and/or marijuana use. Inconsistencies in prevalence, patterns, correlates, and consequences were found between studies, which may be due to large variations in measurement of SAM use, populations studied, methodological design (e.g., cross-sectional vs. intensive longitudinal), and the covariates included in models. CONCLUSIONS: The literature on simultaneous use and same-day co-use of alcohol and marijuana has expanded rapidly. Of the 74 included papers (61 on SAM use; 13 on same-day co-use), 60 papers (47 on SAM use; 13 on same-day co-use) were published within the last 5 years. Future research focusing on the ways in which SAM use confers acute risk, above and beyond the risks associated with separate consumption of alcohol and marijuana, is needed for understanding potential targets for intervention.

Scalable Newborn Screening Solutions: Bioinformatics and Next-Generation Sequencing.

Expansion of the newborn disorder panel requires the incorporation of new testing modalities. This is especially true for disorders lacking robust biomarkers for detection in primary screening methods and for disorders requiring genotyping or sequencing as a second-tier and/or diagnostic test. In this commentary, we discuss how next-generation sequencing (NGS) methods can be used as a secondary testing method in NBS. Additionally, we elaborate on the importance of genomic variant repositories for the annotation and interpretation of variants. Barriers to the incorporation of NGS and bioinformatics within NBS are discussed, and ideas for a regional bioinformatics model and shared variant repository are presented as potential solutions.

[Trombosis due to vena cava inferior agenesia].

This case report describes two 28-year-old healthy males, who werw admitted to hospital due to pain in the lower extremities. Both patients were diagnosed with deep venous thrombosis. In order to determine extent and treatment of the thrombosis, a CT angiography was performed in both patients showing infrarenal vena cava inferior agenesia. Investigation for causes of the thrombosis ruled out cancer and thrombophilia. The patients made full recovery with anticoagulant therapy and compression stockings. Permanent treatment with anticoagulants should be considered in patients with vena cava inferior agenesia.

Effects of within- and between-person assessments of alcohol expectancies and valuations on use and consequences moderated by sex.

BACKGROUND: Alcohol expectancies (AE; beliefs about the likelihood of outcomes) and valuations (beliefs about the desirability of outcomes) may help explain alcohol use by young adults. However, it remains unclear how variability in AE and valuations over time are related to alcohol-related outcomes, and whether these associations are moderated by sex. The current study addressed these gaps in knowledge by examining within-person variability among positive and negative AEs, valuations, and alcohol-related outcomes over a 12-month period. METHODS: Data were collected from 433 college students (Mage  = 20.06; 59.81% women) who completed surveys at 4 timepoints: at baseline and 3-month, 6-month, and 12-month follow-up. RESULTS: We found substantial within-person variability in both AE and valuations (intraclass correlation coefficients ranged from 50% to 66%), and differences in variability by sex, with women showing more variability than men. Multilevel models revealed that weekly drinking was significantly higher at timepoints in which participants held relatively greater AE for sociability, sexuality, and risk/aggression, but lower when participants expected greater effects on self-perception. Weekly drinking was also higher when participants reported more favorable valuation of risk/aggression. Participants experienced significantly more negative consequences at timepoints in which they held relatively greater AE for sexuality and self-perception. No AEs were associated with a reduced likelihood of negative consequences. Participants experienced more negative consequences at timepoints in which they reported more favorable valuation of self-perception No valuations were associated with fewer consequences. Several between- and within-person associations were moderated by sex. CONCLUSIONS: These findings suggest that AE and valuations are dynamic, that young adults' beliefs about the effects of alcohol varied over time, and that both negative and positive AE and valuations may be important correlates of alcohol use and consequences. These findings have implications for interventions designed to challenge expectancies and valuations with the goal of reducing alcohol use and associated consequences.

Methods and feasibility study for exome sequencing as a universal second-tier test in newborn screening.

PURPOSE: Newborn screening disorders increasingly require genetic variant analysis as part of second-tier or confirmatory testing. Sanger sequencing and gene-specific next-generation sequencing (NGS)-based tests, the current methods of choice, are costly and lack scalability when expanding to new conditions. We describe a scalable, exome sequencing-based NGS pipeline with a priori analysis restriction that can be universally applied to any NBS disorder. METHODS: De-identified abnormal newborn screening specimens representing severe combined immune deficiency (SCID), cystic fibrosis (CF), VLCAD deficiency, metachromatic leukodystrophy (MLD), and in silico sequence read data sets were used to validate the pipeline. To support interpretation and clinical decision-making within the bioinformatics pipeline, variants from multiple databases were curated and validated. RESULTS: CFTR variant panel analysis correctly identified all variants. Concordance compared with diagnostic testing results for targeted gene analysis was between 78.6% and 100%. Validation of the bioinformatics pipeline with in silico data sets revealed a 100% detection rate. Varying degrees of overlap were observed between ClinVar and other databases ranging from 3% to 65%. Data normalization revealed that 11% of variants across the databases required manual curation. CONCLUSION: This pipeline allows for restriction of analysis to variants within a single gene or multiple genes, and can be readily expanded to full exome analysis if clinically indicated and parental consent is granted.

Toward newborn screening of metachromatic leukodystrophy: results from analysis of over 27,000 newborn dried blood spots.

PURPOSE: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA), which results in the accumulation of sulfatides. Newborn screening for MLD may be considered in the future as innovative treatments are advancing. We carried out a research study to assess the feasibility of screening MLD using dried blood spots (DBS) from de-identified newborns. METHODS: To minimize the false-positive rate, a two-tier screening algorithm was designed. The primary test was to quantify C16:0-sulfatide in DBS by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The screening cutoff was established based on the results from 15 MLD newborns to achieve 100% sensitivity. The secondary test was to measure the ARSA activity in DBS from newborns with abnormal C16:0-sulfatide levels. Only newborns that displayed both abnormal C16:0-sulfatide abundance and ARSA activity were considered screen positives. RESULTS: A total of 27,335 newborns were screened using this two-tier algorithm, and 2 high-risk cases were identified. ARSA gene sequencing identified these two high-risk subjects to be a MLD-affected patient and a heterozygote. CONCLUSION: Our study demonstrates that newborn screening for MLD is highly feasible in a real-world scenario with near 100% assay specificity.

Impact of physical activity, diet quality and stress on cardiometabolic health in school employees.

Among school employees, it has been reported that poor physical and mental health, as well as high stress and large workloads, have resulted in high absenteeism and low retention. The consequences of unhealthy behaviors and stress can extend to students, impacting academic achievement and school costs. Our objective was to examine the impact of school employees' physical activity (PA), diet quality and perceived occupational stress on cardiometabolic health, and explore how stress may influence the impact of PA and diet on health. In this cross-sectional study, employees from lower-income Massachusetts schools participated in Wellness Assessments (2015-2016), including measured height, weight, and lipids [total (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C)]. Self-administered surveys were used to collect demographic, stress, PA and 24-hour food intake data. Linear regression models were used to examine the relationship among health behaviors (PA and diet), stress and cardiometabolic health. An interaction between stress and health behaviors was also explored. Seventy-four employees (66% teachers) participated. Overweight/obesity (mean BMI: 25.6 kg/m2), high TC and LDL-C were observed in 47%, 4%, and 34%, respectively, and moderate-to-vigorous PA (MVPA) was low (median: 17 min/day). Positive associations were identified between MVPA and cardiometabolic health, but not diet. The effect of MVPA on BMI was modified by stress (p-for-interaction = 0.001), with higher levels of stress associated with a diminished protective association between MVPA and BMI. Higher levels of PA were associated with more favorable cardiometabolic health, with increasing levels of stress minimizing the beneficial effect of PA on BMI.

A Qualitative Investigation of Factors that Influence School Employee Health Behaviors: Implications for Wellness Programming.

BACKGROUND: Employee health promotion in the elementary school setting can support students' health and academic success. School employees can serve as role models, yet evidence suggests poor health in this population. We identified factors that influence school employee health behaviors to inform subsequent development of employee wellness programs. METHODS: Focus groups (10 groups, total N = 62) and interviews (N = 5) were conducted with school employees. Participants were recruited from schools in socioeconomically disadvantaged, racially diverse districts in Massachusetts. We used a socioecological framework to identify multi-level factors that influence employee health behaviors. Factors were characterized as supports (+) or barriers (-) to health-promoting behaviors. RESULTS: Eight themes highlighted the importance of an organizational culture that sustains successful employee wellness programming. Intrapersonal themes included: High Stress (+/-), Desire to Adopt Healthy Behaviors (+), and Sufficient Health Knowledge (+). Interpersonal themes included: Strong Social Network (+) and a Desire to Role Model (+). Organizational themes included: Demanding Job (-), Lack of Wellness Culture (-), and Unhealthy Food (-). CONCLUSIONS: Our findings suggest that this population would be receptive to wellness programming. Promising strategies include supporting a dedicated wellness champion and creating recognizable top down wellness support for employees.

Differential Role of Cannabis Use Motives in Predicting Impairment Across Three Measures.

OBJECTIVE: Previous research has demonstrated the utility of motivational models of cannabis use to predict the frequency of use and associated negative consequences. However, few existing studies have simultaneously investigated a range of motives across different measures of use-related problems, which limit the ability to assess the differential role various motives play. The purpose of the current study was to examine cannabis use motives as predictors of three measures of cannabis use risk. METHOD: Participants (N = 229) who reported cannabis use within the past 30 days completed the Marijuana Motives Measures, as well as measures of typical smoking behavior and risk: Cannabis Use Disorders Identification Test-R (CUDIT-R; screening measure of hazardous cannabis use), Marijuana Problem Index (MPI; measure of broad psychosocial problems), and cannabis use disorder according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). RESULTS: Cannabis use motives-particularly coping, enhancement, and conformity-contributed to the prediction of cannabis-related impairment beyond gender and the frequency of recent use. Among the motives scales, coping emerged as the most robust predictor across the three impairment measures and was the only motive to add unique variance to predictions of DSM-5 symptoms. Enhancement and conformity motives were predictive of the screening measure (CUDIT-R scores), and enhancement motives was also predictive of a measure of broad psychosocial problems related to cannabis use (MPI scores). CONCLUSIONS: The results highlight the differential role various marijuana use motives play across related but distinct measures of impairment.

Evaluation of the psychometric properties of the cannabis use disorders identification test - revised among college students.

OBJECTIVE: Cannabis use is common among college students and is associated with a variety of negative consequences. The Cannabis Use Disorders Identification Test Revised (CUDIT-R) is an 8-item screening instrument designed to identify potentially problematic or harmful recent cannabis use. The purpose of the current study was to evaluate the internal consistency and validity of the CUDIT-R in a sample of college students who reported recent cannabis use (past 30 day). METHODS: Participants (n = 229) completed the CUDIT-R and measures of smoking behavior (Daily Smoking Questionnaire; DSQ), cannabis related consequences (Marijuana Problem Index; MPI), and problematic cannabis use (self-reported DSM-5 Cannabis Use Disorder Criteria). RESULTS: The CUDIT-R showed good internal consistency and concurrent validity with cannabis related outcome measures including; frequency of use, cannabis related consequences, and total DSM-5 criteria endorsed. The CUDIT-R also showed evidence of discriminant validity across DSM-5 severity classifications, achieved high levels of sensitivity (0.929) and specificity (0.704), and excellent area under the receiver operating characteristics curve when using a cutoff score of six. All items displayed high levels of discrimination and varied in terms of difficulty and information provided. CONCLUSIONS: Overall, the CUDIT-R appears to be a reliable and valid screening measure when used to identify college students at risk for cannabis related problems. Future research should further evaluate the sensitivity and specificity of the CUDIT-R threshold scores with more rigorously established DSM-5 diagnoses, and across a range of populations. Research on the utility of using the CUDIT-R for measuring treatment outcomes is also warranted.

Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke.

OBJECTIVE: In this clinical case-control study, we investigated statin treatment in stroke patients on a range of inflammatory effectors in peripheral blood. We focus on RhoA GTPase and its downstream effectors as a future inflammatory target in stroke treatment. METHODS: Data from 10 patients already on statins at stroke onset (Pre-S group) was compared with data from both 29 patients starting statin treatment right after stroke onset (Post-S group) and with 8 healthy controls. In T-cells isolated from stroke patients, we analyzed the activity of the main cytoskeletal regulator RhoA GTPase and its downstream effectors: rho-associated protein kinase (ROCK), myosin phosphatase targeting protein subunit 1 (pMYPT1), myosin light chain kinase (pMLC) and cofilin. In the blood samples, we further determined levels of 12 key plasma cytokines as well as C-reactive protein (CRP) and kallikrein. RESULTS: Compared to healthy controls, the Post-S group achieved significantly higher RhoA and ROCK activities, while the Pre-S did not differ from controls. Levels of pMYPT1, pMLC and cofilin did not differ from controls in the Pre-S and Post-S groups. At day 90 after stroke, interferon γ and IL-18 were significantly increased in the Post-S group compared to the Pre-S group. We found a positive correlation between CRP and NIHSS, whereas kallikrein levels showed no correlation with NIHSS at any of the days. CONCLUSION: Stroke induces changes in the RhoA-ROCK pathway in T-cells. CRP and NIHSS score correlated positively in the study. Statins may have an anti-inflammatory effect as statin treatment before stroke reduces post-stroke pro-inflammatory levels. RhoA GTPase and its downstream effectors are possibly the key to improve statin treatment in stroke.

Investigating best practices of district-wide physical activity programmatic efforts in US schools- a mixed-methods approach.

BACKGROUND: The majority of US children do not meet physical activity recommendations. Schools are an important environment for promoting physical activity in children, yet most school districts do not offer enough physical activity opportunities to meet recommendations. This study aimed to identify school districts across the country that demonstrated exemplary efforts to provide students with many physical activity opportunities and to understand the factors that facilitated their programmatic success. METHODS: A total of 59 districts were identified as model districts by members of the Physical Activity and Health Innovation Collaborative, an ad hoc activity associated with the Roundtable on Obesity Solutions at the National Academies of Sciences, Engineering, and Medicine. Semi-structured interviews were conducted with consenting stakeholders from 23 school districts to understand physical education and activity efforts and elucidate factors that led to the success of these districts' physical activity programming. Districts were geographically and socioeconomically diverse and varied in their administrative and funding structure. RESULTS: Most districts did not offer the recommended 150 or 225 min of physical activity a week through physical education alone; yet all districts offered a range of programs outside of physical education that provided additional opportunities for students to be physically active. The average number of school-based physical activity programs offered was 5.5, 3.5 and 2.1 for elementary, middle and high schools, respectively. Three overarching and broadly relevant themes were identified that were associated with successfully enhancing physical activity opportunities for students: soliciting and maintaining the support of champions, securing funding and/or tangible support, and fostering bi-directional partnerships between the district and community organizations and programs. Not only were these three themes critical for the development of physical activity opportunities, but they also remained important for the implementation, evaluation and sustainability of programs. These themes also did not differ substantially by the socioeconomic status of districts. CONCLUSIONS: These findings demonstrate the success of school districts across the nation in providing ample opportunities for physical activity despite considerable variability in socioeconomic status and resources. These results can inform future research and provide actionable evidence for school districts to enhance physical activity opportunities to students.

ClinVar Miner: Demonstrating utility of a Web-based tool for viewing and filtering ClinVar data.

ClinVar Miner is a Web-based suite that utilizes the data held in the National Center for Biotechnology Information's ClinVar archive. The goal is to render the data more accessible to processes pertaining to conflict resolution of variant interpretation as well as tracking details of data submission and data management for detailed variant curation. Here, we establish the use of these tools to address three separate use cases and to perform analyses across submissions. We demonstrate that the ClinVar Miner tools are an effective means to browse and consolidate data for variant submitters, curation groups, and general oversight. These tools are also relevant to the variant interpretation community in general.