Psychological distress and alcohol use disorder in college students of color: Social support's moderating properties.

Alcohol use is prevalent among college students. Research has found that psychological distress in the form of depression, anxiety, or loneliness has been consistently associated with greater alcohol use. Because Students of Color (SoC) disproportionately experience greater psychological distress than White students, it is critical to determine buffers against psychological distress and subsequent alcohol use consequences. Previous literature found that social support can protect against the effects of psychological distress and weaken its link with alcohol use. This study aimed to determine the moderating effect of social support in the relation between psychological distress and alcohol use among SoC. College Students of Color from across the U.S. (n = 211, Mage = 27.51, SD = 9.63) were recruited via Prolific to answer an online survey through Qualtrics. Linear regression analyses showed that psychological distress variables (i.e., depression, anxiety, and loneliness) were positively associated with alcohol use. However, moderation analysis did not find any form of social support to moderate the relation between psychological distress variables and alcohol use. Future research needs to identify other protective factors against alcohol use to support SoC in their academic journey.

Impact of a Cancer Education Curriculum on Appalachian Kentucky Middle and High School Students.

Appalachian Kentucky is disproportionately affected by elevated cancer incidence and mortality rates. This disparity is driven by inequities in health behaviors and social determinants of health including decreased education attainment levels that cause lower health literacy. To increase cancer literacy in the region, a three-part cancer education curriculum was designed for Appalachian Kentucky middle and high school students. This study was designed to evaluate the effect the curriculum had on students' cancer literacy. The curriculum lessons were disseminated to Appalachian Kentucky middle and high school teachers who engaged 223 students with the material. For each lesson, students filled out a 10-question pretest and an identical 10-question posttest. The average and median percent of correct responses from the pre- to posttests were analyzed. The average percentage of correct responses significantly increased from 40% to 70%, 52% to 69%, and 33% to 53% on lessons 1, 2, and 3, respectively. A significant increase in the average percentage of correct responses on each individual question was also observed. The results demonstrate that the three-part cancer education curriculum intervention can significantly increase Appalachian Kentucky middle and high school students' cancer literacy. Increased cancer knowledge has the potential to encourage behavioral modifications that could reduce cancer incidence and mortality rates over time. Future work will include further improving the content relative to the target age/grade level and implementing the material with a broader group of teachers and students.

Associations of Anaplasma phagocytophilum Bacteria Variants in Ixodes scapularis Ticks and Humans, New York, USA.

Anaplasmosis, caused by the tickborne bacterium Anaplasma phagocytophilum, is an emerging public health threat in the United States. In the northeastern United States, the blacklegged tick (Ixodes scapularis) transmits the human pathogenic genetic variant of A. phagocytophilum (Ap-ha) and a nonpathogenic variant (Ap-V1). New York has recently experienced a rapid and geographically focused increase in cases of anaplasmosis. We analyzed A. phagocytophilum-infected I. scapularis ticks collected across New York during 2008-2020 to differentiate between variants and calculate an entomological risk index (ERI) for each. Ap-ha ERI varied between regions and increased in all regions during the final years of the study. Space-time scan analyses detected expanding clusters of Ap-ha located within documented anaplasmosis hotspots. Ap-ha ERI was more positively correlated with anaplasmosis incidence than non-genotyped A. phagocytophilum ERI. Our findings help elucidate the relationship between the spatial ecology of A. phagocytophilum variants and anaplasmosis.

Mobile Phone Apps for Intimate Partner and Sexual Violence Prevention and Response: Systematic Search on App Stores.

BACKGROUND: Since the 2008 advent of the smartphone, more than 180 billion copies of apps have been downloaded from Apple App Store, with more than 2.6 million apps available for Android and 2.2 million apps available for iOS. Many violence prevention and response apps have been developed as part of this app proliferation. OBJECTIVE: This study aims to evaluate the prevalence and quality of freely available mobile phone apps targeting intimate partner violence (IPV) and sexual violence (SV) prevention and response. METHODS: We conducted a systematic search of violence prevention and response mobile phone apps freely available in Apple App Store (iOS; March 2016) and Google Play Store (Android; July 2016). Search terms included violence prevention, sexual assault, domestic violence, intimate partner violence, sexual violence, forensic nursing, wife abuse, and rape. Apps were included for review if they were freely available, were available in English, and had a primary purpose of prevention of or response to SV or IPV regardless of app target end users. RESULTS: Using the Mobile Application Rating Scale (MARS), we evaluated a total of 132 unique apps. The majority of included apps had a primary purpose of sharing information or resources. Included apps were of low-to-moderate quality, with the overall subjective quality mean for the reviewed apps being 2.65 (95% CI 2.58-2.72). Quality scores for each of the 5 MARS categories ranged from 2.80 (engagement) to 4.75 (functionality). An incidental but important finding of our review was the difficulty in searching for apps and the plethora of nonrelated apps that appear when searching for keywords such as "rape" and "domestic violence" that may be harmful to people seeking help. CONCLUSIONS: Although there are a variety of mobile apps available designed to provide information or other services related to SV and IPV, they range greatly in quality. They are also challenging to find, given the current infrastructure of app store searches, keyword prioritization, and highlighting based on user rating. It is important for providers to be aware of these resources and be knowledgeable about how to review and recommend mobile phone apps to patients, when appropriate.

Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility.

BACKGROUND: Right ventricular dysfunction (RVD) is the leading cause of death in pulmonary arterial hypertension (PAH), but no RV-specific therapy exists. We showed microtubule-mediated junctophilin-2 dysregulation (MT-JPH2 pathway) causes t-tubule disruption and RVD in rodent PAH, but the druggable regulators of this critical pathway are unknown. GP130 (glycoprotein 130) activation induces cardiomyocyte microtubule remodeling in vitro; however, the effects of GP130 signaling on the MT-JPH2 pathway and RVD resulting from PAH are undefined. METHODS: Immunoblots quantified protein abundance, quantitative proteomics defined RV microtubule-interacting proteins (MT-interactome), metabolomics evaluated the RV metabolic signature, and transmission electron microscopy assessed RV cardiomyocyte mitochondrial morphology in control, monocrotaline, and monocrotaline-SC-144 (GP130 antagonist) rats. Echocardiography and pressure-volume loops defined the effects of SC-144 on RV-pulmonary artery coupling in monocrotaline rats (8-16 rats per group). In 73 patients with PAH, the relationship between interleukin-6, a GP130 ligand, and RVD was evaluated. RESULTS: SC-144 decreased GP130 activation, which normalized MT-JPH2 protein expression and t-tubule structure in the monocrotaline RV. Proteomics analysis revealed SC-144 restored RV MT-interactome regulation. Ingenuity pathway analysis of dysregulated MT-interacting proteins identified a link between microtubules and mitochondrial function. Specifically, SC-144 prevented dysregulation of electron transport chain, Krebs cycle, and the fatty acid oxidation pathway proteins. Metabolomics profiling suggested SC-144 reduced glycolytic dependence, glutaminolysis induction, and enhanced fatty acid metabolism. Transmission electron microscopy and immunoblots indicated increased mitochondrial fission in the monocrotaline RV, which SC-144 mitigated. GP130 antagonism reduced RV hypertrophy and fibrosis and augmented RV-pulmonary artery coupling without altering PAH severity. In patients with PAH, higher interleukin-6 levels were associated with more severe RVD (RV fractional area change 23±12% versus 30±10%, P=0.002). CONCLUSIONS: GP130 antagonism reduces MT-JPH2 dysregulation, corrects metabolic derangements in the RV, and improves RVD in monocrotaline rats.

Alternate Light Source Findings of Common Topical Cosmetics and Three Removal Methods.

INTRODUCTION: Alternate light sources (ALSs) are a tool used by forensic nurses to aid in the physical examination of patients. Prior research has shown some topical makeup products absorb alternate light similar to the absorption noted in bruises. Therefore, the purposes of this study were (a) to further examine the ALS findings of multiple brands and types of makeup products and (b) to compare the efficacy of three methods of makeup removal. METHODS: Fourteen makeup products were applied to the forearms of 100 healthy adult volunteers with varying skin tones and then assessed under white light, six alternate light wavelengths, and three color filters, producing 19 total wavelength-and-filter combinations. The results were recorded before and after removal procedures by forensic nurse examiners who were blinded to the removal method. A three-arm randomized controlled trial of makeup removal methods (soap and water, isopropyl alcohol swab, makeup removal wipe) was conducted with the participants. RESULTS: All 14 makeup products produced absorption in at least 10% of the observations. Fluorescence was observed in more than 10% of the observations for only two products. After product removal, four products continued to produce statistically significant absorption findings when viewed under an ALS. One product produced significant fluorescence after removal procedures. There were no statistically significant differences between the removal methods noted in any of these analyses. CONCLUSION: Our findings support the importance of using alternate light as one component of a comprehensive forensic examination, including history taking and physical examination.

The Positive Impact and Associated Mechanisms of Physical Activity on Mental Health in Underprivileged Children and Adolescents: An Integrative Review.

(1) Background: Review-based studies are required to consider the different designs and data that describe the association between physical activity and mental health for underprivileged children and adolescents. There is a particular need to identify mechanisms which could explain the association, and factors which influence the association in this population group. (2) Methods: An integrative review with a systematic search was conducted in three stages: (i) a systematic literature search on four databases from inception until May 2020. Studies were eligible if they examined underprivileged children, involved moderate to vigorous physical activity (MVPA) and had a focus on at least one outcome measure related to mental health. (ii) Two critical appraisal tools were used to assess quality across different study designs. (iii) Synthesis was undertaken in four stages, examining social, internal and physical outcomes and mechanisms. (3) Results: A total of 16 studies were included (2 qualitative; 12 quantitative and 2 mixed methods). Fifteen (15/16; 93.8%) showed an association between MVPA and a significant improvement in at least one mental health outcome. The most studied outcomes included: internal aspects (n = 14), significant effects were identified in 12/14 studies; social aspects (n = 6), significant effects were identified across all studies and finally physical aspects (n = 5), significant effects were found in 3/5 studies. Autonomy support was identified as a mechanism to explain the change, whilst age and gender influenced the strength of the association. (4) Conclusions: The findings provide confirmation of the link between MVPA and the improved mental health and wellbeing of disadvantaged children and adolescents. Future research must consider the long-term effect through longitudinal studies, along with determining whether any specific types of PA are more impactful than others.

Excess Protein O-GlcNAcylation Links Metabolic Derangements to Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.

The hexosamine biosynthetic pathway (HBP) converts glucose to uridine-diphosphate-N-acetylglucosamine, which, when added to serines or threonines, modulates protein function through protein O-GlcNAcylation. Glutamine-fructose-6-phosphate amidotransferase (GFAT) regulates HBP flux, and AMP-kinase phosphorylation of GFAT blunts GFAT activity and O-GlcNAcylation. While numerous studies demonstrate increased right ventricle (RV) glucose uptake in pulmonary arterial hypertension (PAH), the relationship between O-GlcNAcylation and RV function in PAH is unexplored. Therefore, we examined how colchicine-mediated AMP-kinase activation altered HBP intermediates, O-GlcNAcylation, mitochondrial function, and RV function in pulmonary artery-banded (PAB) and monocrotaline (MCT) rats. AMPK activation induced GFAT phosphorylation and reduced HBP intermediates and O-GlcNAcylation in MCT but not PAB rats. Reduced O-GlcNAcylation partially restored the RV metabolic signature and improved RV function in MCT rats. Proteomics revealed elevated expression of O-GlcNAcylated mitochondrial proteins in MCT RVs, which fractionation studies corroborated. Seahorse micropolarimetry analysis of H9c2 cardiomyocytes demonstrated colchicine improved mitochondrial function and reduced O-GlcNAcylation. Presence of diabetes in PAH, a condition of excess O-GlcNAcylation, reduced RV contractility when compared to nondiabetics. Furthermore, there was an inverse relationship between RV contractility and HgbA1C. Finally, RV biopsy specimens from PAH patients displayed increased O-GlcNAcylation. Thus, excess O-GlcNAcylation may contribute to metabolic derangements and RV dysfunction in PAH.

Hypochloremia Is a Noninvasive Predictor of Mortality in Pulmonary Arterial Hypertension.

Background Pulmonary arterial hypertension (PAH) is a lethal disease. In resource-limited countries PAH outcomes are worse because therapy costs are prohibitive. To improve global outcomes, noninvasive and widely available biomarkers that identify high-risk patients should be defined. Serum chloride is widely available and predicts mortality in left heart failure, but its prognostic utility in PAH requires further investigation. Methods and Results In this study 475 consecutive PAH patients evaluated at the University of Minnesota and Vanderbilt University PAH clinics were examined. Clinical characteristics were compared by tertiles of serum chloride. Both the Kaplan-Meier method and Cox regression analysis were used to assess survival and predictors of mortality, respectively. Categorical net reclassification improvement and relative integrated discrimination improvement compared prediction models. PAH patients in the lowest serum chloride tertile (≤101 mmol/L: hypochloremia) had the lowest 6-minute walk distance and highest right atrial pressure despite exhibiting no differences in pulmonary vascular disease severity. The 1-, 3-, and 5-year survival was reduced in hypochloremic patients when compared with the middle- and highest-tertile patients (86%/64%/44%, 95%/78%/59%, and, 91%/79%/66%). After adjustment for age, sex, diuretic use, serum sodium, bicarbonate, and creatinine, the hypochloremic patients had increased mortality when compared with the middle-tertile and highest-tertile patients. The Minnesota noninvasive model (functional class, 6-minute walk distance, and hypochloremia) was as effective as the French noninvasive model (functional class, 6-minute walk distance, and elevated brain natriuretic peptide or N-terminal pro-brain natriuretic peptide) for predicting mortality. Conclusions Hypochloremia (≤101 mmol/L) identifies high-risk PAH patients independent of serum sodium, renal function, and diuretic use.

Clinical Determinants and Prognostic Implications of Right Ventricular Dysfunction in Pulmonary Hypertension Caused by Chronic Lung Disease.

Background Patients with pulmonary hypertension caused by chronic lung disease (Group 3 PH ) have disproportionate right ventricle ( RV ) dysfunction, but the correlates and clinical implications of RV dysfunction in Group 3 PH are not well defined. Methods and Results We performed a cohort study of 147 Group 3 PH patients evaluated at the University of Minnesota. RV systolic function was quantified using right ventricular fractional area change ( RVFAC ) and + dP /dtmax/instantaneous pressure. Tau and RV diastolic stiffness characterized RV diastolic function. Multivariate linear regression was used to define correlates of RVFAC . Kaplan-Meier and Cox proportional hazards analyses were used to examine freedom from heart failure hospitalization and death. Positive correlates of RVFAC on univariate analysis were pulmonary arterial compliance, cardiac index, and left ventricular diastolic dimension. Conversely, male sex, N-terminal pro-brain natriuretic peptide, heart rate, right atrial enlargement, mean pulmonary arterial pressure, and pulmonary vascular resistance were negative correlates. Male sex was the strongest predictor of lower RVFAC , after adjusting for pulmonary vascular resistance and pulmonary arterial compliance. When comparing sexes, males had lower RVFAC (26% versus 31%, P=0.03) both overall and for any given mean pulmonary arterial pressure and pulmonary vascular resistance value. Males exhibited a reduction in + dP /dtmax/instantaneous pressure as pulmonary vascular resistance increased, whereas females did not. There were no sex differences in RV diastolic function. RV dysfunction ( RVFAC <28%) was associated with increased risk of heart failure hospitalization or death (hazard ratio: 1.84, 95% CI : 1.04-3.10, P=0.035). Conclusions Male sex is associated with RV dysfunction in Group 3 PH , even after adjusting for RV afterload. RV dysfunction ( RVFAC <28%) identifies Group 3 PH patients at risk for poor outcomes.

Survival in pulmonary hypertension due to chronic lung disease: Influence of low diffusion capacity of the lungs for carbon monoxide.

BACKGROUND: Patients with pulmonary hypertension (PH) due to chronic lung disease (Group 3 PH) have poor long-term outcomes. However, predictors of survival in Group 3 PH are not well described. METHODS: We performed a cohort study of Group 3 PH patients (n = 143; mean age 65 ± 12 years, 52% female) evaluated at the University of Minnesota. The Kaplan-Meier method and Cox regression analysis were used to assess survival and predictors of mortality, respectively. The clinical characteristics and survival were compared in patients categorized by PH severity based on the World Health Organization (WHO) classification and lung disease etiology. RESULTS: After a median follow-up of 1.4 years, there were 69 (48%) deaths. The 1-, 3-, and 5-year survival rates were 79%, 48%, and 31%. Age, coronary artery disease, atrial fibrillation, Charlson comorbidity index, serum N-terminal pro‒brain natriuretic peptide (NT-proBNP), creatinine, diffusion capacity of carbon monoxide (DLCO), total lung capacity, left ventricular ejection fraction, right atrial and right ventricular enlargement on echocardiography, cardiac index, and pulmonary vascular resistance (PVR) were univariate predictors of survival. On multivariable analysis, DLCO was the only predictor of mortality (adjusted hazard ratio [HR] for every 10% decrease in predicted value: 1.31 [95% confidence interval 1.12 to 1.47]; p = 0.003). The 1-/5-year survival by tertiles of DLCO was 84%/56%, 82%/44%, and 63%/14% (p = 0.01), respectively. On receiver-operating characteristic curve analysis, DLCO <32% of predicted had the highest sensitivity and specificity for predicting survival. The 1- and 5-year survival in patients with a DLCO ≥32% predicted was 84% and 60% vs 68% and 13% in patients with a DLCO <32% predicted (adjusted HR: 2.5 [95% confidence interval 1.3 to 5.0]; p = 0.007). Lung volumes and DLCO were not related, but higher PVR was strongly associated with reduced DLCO. There was increased mortality in interstitial lung disease‒PH as compared with chronic obstructive pulmonary disease‒PH, but PH severity based on the WHO classification did not alter survival. CONCLUSIONS: Low DLCO is a predictor of mortality and should be used to risk-stratify Group 3 PH patients.

Interleukin-6 is independently associated with right ventricular function in pulmonary arterial hypertension.

BACKGROUND: An elevated serum level of interleukin-6 (IL-6) in pulmonary arterial hypertension (PAH) patients results in a greater symptom burden and increased mortality; however, the mechanisms underlying these observations remain unclear. Because both pre-clinical and clinical data associate elevated IL-6 levels with impaired cardiac function, we hypothesized that the adverse effects of IL-6 in PAH result, in part, from right ventricular (RV) dysfunction. METHODS: We analyzed the relationship between IL-6 and RV function in 40 patients with PAH identified in our institutional PAH registry. Serum IL-6 levels was quantified by enzyme-linked immunoassay. RESULTS: PAH patients had higher IL-6 levels than age- and gender-matched controls. Circulating IL-6 levels correlated inversely with echocardiography-based measures of RV function and RV-pulmonary artery (RV-PA) coupling. When dividing PAH patients by median IL-6 level, patients with higher IL-6 had significantly worse RV function (fractional area change [FAC] 23 ± 12% vs 38 ± 11%, tricuspid annular plane systolic excursion [TAPSE] 1.3 ± 0.3 cm vs 2.1 ± 0.5 cm), impaired RV-PA coupling (0.6 ± 0.5%/mm Hg vs 0.9 ± 0.5%/mm Hg), higher right atrial pressure (13 ± 7 mm Hg vs 9 ± 5 mm Hg), reduced cardiac index (2.0 ± 0.5 liters/min/m2 vs 2.8 ± 1.0 liters/min/m2) and lower stroke volume (48 ± 20 ml vs 70 ± 28 ml). In contrast, the relationships between IL-6 and mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PAC) were not significant. Finally, IL-6 was independently associated with RV function and RV-PA coupling after adjusting for static (PVR) and pulsatile (PAC) after-load on the RV. CONCLUSIONS: Serum IL-6 levels are independently associated with RV function and RV-PA coupling in PAH. Patients with higher IL-6 levels have more severe RV dysfunction and diminished RV-PA coupling despite a comparable severity of pulmonary vascular disease.

Pulmonary pulse wave transit time is associated with right ventricular-pulmonary artery coupling in pulmonary arterial hypertension.

Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular-pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC (r = 0.64, P < 0.0001), TAPSE (r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression.

Three-year follow-up of an early childhood intervention: what about physical activity and weight status?

BACKGROUND: Fundamental movement skills are a correlate of physical activity and weight status. Children who participated in a preschool intervention had greater movement skill proficiency and improved anthropometric measures (waist circumference and BMI z scores) post intervention. Three years later, intervention girls had retained their object control skill advantage. The study purpose was to assess whether at 3-year follow up a) intervention children were more physically active than controls and b) the intervention effect on anthropometrics was still present. METHODS: Children were assessed at ages 4, 5, and 8 years for anthropometric measures and locomotor and object control proficiency (Test of Gross Motor Development-2). At age 8, children were also assessed for moderate to vigorous physical activity (MVPA) (using accelerometry). Several general linear models were run, the first with MVPA as the outcome, intervention/control, anthropometrics, object control and locomotor scores as predictors, and age and sex as covariates. The second and third models were similar, except baseline to follow-up anthropometric differences were the outcome. RESULTS: Overall follow-up rate was 29% (163/560), with 111 children having complete data. There were no intervention control differences in either MVPA or anthropometrics. CONCLUSION: Increased skill competence did not translate to increased physical activity.

Making sense in a complex landscape: how the Cynefin Framework from Complex Adaptive Systems Theory can inform health promotion practice.

Health promotion addresses issues from the simple (with well-known cause/effect links) to the highly complex (webs and loops of cause/effect with unpredictable, emergent properties). Yet there is no conceptual framework within its theory base to help identify approaches appropriate to the level of complexity. The default approach favours reductionism--the assumption that reducing a system to its parts will inform whole system behaviour. Such an approach can yield useful knowledge, yet is inadequate where issues have multiple interacting causes, such as social determinants of health. To address complex issues, there is a need for a conceptual framework that helps choose action that is appropriate to context. This paper presents the Cynefin Framework, informed by complexity science--the study of Complex Adaptive Systems (CAS). It introduces key CAS concepts and reviews the emergence and implications of 'complex' approaches within health promotion. It explains the framework and its use with examples from contemporary practice, and sets it within the context of related bodies of health promotion theory. The Cynefin Framework, especially when used as a sense-making tool, can help practitioners understand the complexity of issues, identify appropriate strategies and avoid the pitfalls of applying reductionist approaches to complex situations. The urgency to address critical issues such as climate change and the social determinants of health calls for us to engage with complexity science. The Cynefin Framework helps practitioners make the shift, and enables those already engaged in complex approaches to communicate the value and meaning of their work in a system that privileges reductionist approaches.

Three year follow-up of an early childhood intervention: is movement skill sustained?

BACKGROUND: Movement skill competence (e.g. the ability to throw, run and kick) is a potentially important physical activity determinant. However, little is known about the long-term impact of interventions to improve movement skills in early childhood. This study aimed to determine whether intervention preschool children were still more skill proficient than controls three years after a 10 month movement skill focused intervention: 'Tooty Fruity Vegie in Preschools'. METHODS: Children from 18 intervention and 13 control preschools in NSW, Australia were assessed at ages four (Time1), five (T2) and eight years (T3) for locomotor (run, gallop, hop, leap, horizontal jump, slide) and object control proficiency (strike, bounce, catch, kick, overhand throw, underhand roll) using the Test of Gross Motor Development-2. Multi-level object control and locomotor regression models were fitted with variables time, intervention (yes/no) and a time*intervention interaction. Both models added sex of child and retained if significant, in which case interactions of sex of child with other variables were modelled and retained. SPSS (Version 17.0) was used. RESULTS: Overall follow-up rate was 29% (163/560). Of the 137 students used in the regression models, 53% were female (n = 73). Intervention girls maintained their object control skill advantage in comparison to controls at T3 (p = .002), but intervention boys did not (p = .591). At T3, there were no longer intervention/control differences in locomotor skill (p = .801). CONCLUSION: Early childhood settings should implement movement skill interventions and more intensively target girls and object control skills.

Prevalence of abnormal liver-associated enzymes in cocaine experienced adults versus healthy volunteers during phase 1 clinical trials.

The frequency and nature of elevation of liver-associated enzymes (LAE) are important safety endpoints in Phase 1 clinical trials of new anti-cocaine agents, yet very little information is available on the prevalence of abnormal LAE in cocaine experienced adults. The aim of this retrospective study was to investigate the alterations of liver-associated enzymes (LAE) aspartate- (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin in healthy "normal" (HN) and cocaine experienced (actively using cocaine preadmission (CE)) adults participating in long term inpatient clinical trials. We examined LAE values collected from 3 inpatient Phase 1 trials of anti-cocaine agents. Analysis of variance (ANOVA) was applied to determine the significance of various factors on LAE alterations. Gender, baseline BMI, treatment did not demonstrate significant group differences in LAE levels. CE study volunteers were found to have significantly higher AST and ALT values than HN volunteers (P<0.05) during their respective inpatient stays. 94.1% of the 17 subjects with abnormal LAE were CE, and 37.5% of these CE received placebo. In conclusion, despite normal baseline values, most subjects demonstrated an increase in the ALT level even on placebo. For CE subjects, differences (Delta ALT and Delta AST) between baseline and the maximum observed values were significantly higher than that observed for HN subjects. The potential to obscure important signals for hepatotoxicity during Phase 1 research may be higher in the CE study population.