Clustered Cardiometabolic Risk, Cardiorespiratory Fitness and Physical Activity in 10-11 Year-Old Children. The CHANGE! Project Baseline

Objectives: The primary objective of this cross sectional pilot study was to report clustered risk scores combining traditional invasive with non invasive cardiometabolic risk markers in 10-11 year old children participating in the CHANGE! project at baseline. A secondary objective was to determine the relationship between clustered risk score and objectively measured physical activity (PA) and cardiorespiratory fitness (CRF). Methods: Habitual PA was measured using accelerometry and CRF (VO2peak) was assessed using an individually calibrated treadmill based protocol. Twenty-nine participants had valid data for all components of the clustered risk score, calculated using total cholesterol: high density lipoprotein-cholesterol (TC:HDL-C), glucose, systolic blood pressure (BP), LV Mass Index (g/m2.7), and trunk fat mass (g). Participants with a clustered risk score greater than 1SD above the mean, were categorised as ‘higher’ risk (n=6); all others were categorised as ‘normal’ risk. \ud \ud Results: Clustered risk score, controlling for somatic maturity and gender, was negatively correlated with VPA (r= -0.51, p=0.01), MVPA (r= -0.44, p=0.03) and VO2peak (r= -0.57, p<0.01). ANCOVA, with somatic maturity and gender as covariates, revealed that those in the ‘normal’ risk group were more fit than those in the ‘higher’ risk group [f (1,24)=4.518, p=0.044]). There were no statistically significant differences between risk groups and PA however mean data suggest that those in the ‘normal’ risk group accrued 4 minutes more daily VPA than the ‘higher’ risk group which may be clinically important. \ud \ud Conclusions: This provides further evidence of the importance of promoting CRF and VPA in children, to reduce cardiometabolic risk especially for those that are ‘higher’ risk

A cross-sectional study on the deprivation and sex differences in health-related fitness measures in school children

This study aimed to investigate deprivation and sex differences in selected health-relatedfitness measures in 9-12-year-old children. Data were captured on 3,407 children (49.3% boys; aged 10.5 ± 0.6 years). Cardiorespiratory fitness(20 m multistage shuttle run test; 20 m MSRT), muscular strength (handgrip strength) and body mass index (BMI) were measured. Welsh Index of Multiple Deprivation (WIMD) scores were used to make quintile groups. A two-way Analysis of Variance examined differences in BMI z-score by sex and WIMD quintiles. Two-wayAnalysis of Covariances investigated the effect of sex and WIMD quintiles on grip strength and shuttles achieved in 20 m MSRT, adjusting for BMI z-score and maturation, repectively. Independent of sex, children in the middle quintile had a significantly higher mean BMI z-score (p = 0.029) than their least deprived counterparts. There was a significant increase in grip strength (p = 0.005) and20 m MSRT (boys p < 0.001; girls p = 0.028) between most and least deprived quintiles. Significant differences in 20 m MSRT score were more apparent with decreases in deprivation in boys.Overall, inequalities exist in health-related fitness by sex and deprivation. These results can be used to inform focused services to improve current and future health

MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

ABSTRACT While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends to in vivo models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward. IMPORTANCE The initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

Assessment of hepatitis C monitoring adherence after viral eradication in veterans with substance use to improve care and surveil reinfection

Introduction: Hepatitis C virus (HCV) incidence rates are rising for patients with substance use and/or SUDs. Guidelines provide monitoring recommendations to ensure remission after successful treatment. The study's objective was to identify gaps in follow-up for patients with documented substance use and/or SUD through assessment of adherence to guideline-recommended HCV RNA lab 12 months post-treatment. Methods: Patients treated for HCV through the Veteran Health Indiana Hepatitis C Pharmacy Clinic were retrospectively evaluated. Subjects were categorized based on the provider assigned for follow-up care after 12-week sustained virologic response (SVR12) labs (primary care provider [PCP] or HCV provider). The primary outcome was HCV RNA obtained 11 to 13 months post-treatment. Secondary outcomes were HCV RNA detected post-treatment, substance use, engagement in substance use treatment, and engagement with social work. Results: Two hundred forty-one patients were included in the HCV provider cohort and 139 in the PCP cohort. Forty-one patients did not have a specified clinic for follow-up treatment, and 20 patients did not achieve SVR12. Sixty-one patients (28%) in the HCV provider cohort completed a 12-month HCV RNA within 11 to 13 months post-treatment vs 15 patients (11%) in the PCP cohort (P ≤ .01). One patient had HCV RNA detected post-treatment. Discussion: This study reveals inadequate HCV post-treatment follow-up for patients with substance use and/or SUD. SUD is a chronic disease that requires continued monitoring to prevent complications. Further studies are needed to identify reinfection rates and improvements of care in this population

Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial

SummaryBackgroundHospitalized, malnourished older adults have a high risk of readmission and mortality.ObjectiveEvaluation of a high-protein oral nutritional supplement (HP-HMB) containing beta-hydroxy-beta-methylbutyrate on postdischarge outcomes of nonelective readmission and mortality in malnourished, hospitalized older adults.DesignMulticenter, randomized, placebo-controlled, double-blind trial.SettingInpatient and posthospital discharge.PatientsOlder (≥65 years), malnourished (Subjective Global Assessment [SGA] class B or C) adults hospitalized for congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease.InterventionsStandard-of-care plus HP-HMB (n = 328) or a placebo supplement (n = 324), 2 servings/day.MeasurementsPrimary composite endpoint was 90-day postdischarge incidence of death or nonelective readmission. Other endpoints included 30- and 60-day postdischarge incidence of death or readmission, length of stay (LOS), SGA class, body weight, and activities of daily living (ADL).ResultsThe primary composite endpoint was similar between HP-HMB (26.8%) and placebo (31.1%). No between-group differences were observed for 90-day readmission rate, but 90-day mortality was significantly lower with HP-HMB relative to placebo (4.8% vs. 9.7%; relative risk 0.49, 95% confidence interval [CI], 0.27 to 0.90; p = 0.018). The number-needed-to-treat to prevent 1 death was 20.3 (95% CI: 10.9, 121.4). Compared with placebo, HP-HMB resulted in improved odds of better nutritional status (SGA class, OR, 2.04, 95% CI: 1.28, 3.25, p = 0.009) at day 90, and an increase in body weight at day 30 (p = 0.035). LOS and ADL were similar between treatments.LimitationsLimited generalizability; patients represent a selected hospitalized population.ConclusionsAlthough no effects were observed for the primary composite endpoint, compared with placebo HP-HMB decreased mortality and improved indices of nutritional status during the 90-day observation period.Clinical trial registrationwww.ClinicalTrials.gov NCT01626742

Active children through incentive vouchers – evaluation (ACTIVE): a mixed-method feasibility study

BackgroundAdolescents face many barriers to physical activity, demonstrated by the decline in physical activity levels in teenage populations. This study aimed to assess the feasibility of overcoming such barriers via the implementation of an activity-promoting voucher scheme to teenagers in deprived areas.MethodsAll Year 9 pupils (n = 115; 13.3 ± 0.48 years; 51 % boys) from one secondary school in Wales (UK) participated. Participants received £25 of activity vouchers every month for six months for physical activity or sporting equipment. Focus groups (n = 7), with 43 pupils, and qualitative interviews with teachers (n = 2) were conducted to assess feasibility, in addition to a process evaluation utilising the RE-AIM framework. Quantitative outcomes at baseline, five months (during intervention) and twelve months (follow-up) included: physical activity (accelerometer), aerobic fitness (12 min Cooper run) and self-reported activity (PAQ-A). Motivation to exercise (BREQ-2) was measured three months post-baseline and at follow-up.ResultsQualitative findings showed that vouchers encouraged friends to socialise through activity, provided opportunities to access local activities that pupils normally could not afford, and engaged both those interested and disinterested in physical education. Improvements in weekend moderate-to-vigorous physical activity and reductions in sedentary behaviour were observed in both sexes. Boys’ fitness significantly improved during the voucher scheme. ‘Non-active’ pupils (those not meeting recommended guidelines of 60 mins∙day−1) and those with higher motivation to exercise had higher voucher use.ConclusionsAdolescents, teachers and activity providers supported the voucher scheme and felt the vouchers enabled deprived adolescents to access more physical activity opportunities. Voucher usage was associated with improved attitudes to physical activity, increased socialisation with friends and improved fitness and physical activity; presenting interesting avenues for further exploration in a larger intervention trial

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas