An educational intervention to promote healthy lifestyles in preschool children: a cluster-RCT

OBJECTIVE: Promoting four healthy behaviours among preschool children:⩾4 servings of fruit and vegetables/day, ⩾2 h/day of active play, ⩽1 h per day of TV-watching and 0 sugar sweetened beverages/day. METHODS: We conducted a c-RCT on 425 3-year-old children at 16 childcare centres based in Cesena, Italy. We randomly allocated eight childcare centres (199 children) to the intervention group and eight childcare centres (226 children) to the control group. All the randomized childcare centres completed our study protocol. Parents recorded their children's target behaviours at home over 3 Saturdays, at baseline and at follow-up. Then trained nurses measured children's weight and height. We conducted a 6-month-long intervention trial in local health care centres where nurses and primary care pediatricians, respectively, conducted two subsequent motivational interviews with parents to encourage children's healthy behaviours at home. At the same time, teachers involved children in learning experiences about healthy behaviours. Our primary outcome is a children's combined health behaviour score (CHBS) at home. Our secondary outcomes measure the BMI z-score and the percentage of children that show a BMI trajectory crossing upward. After collecting the CHBS and BMI data at baseline as well as at 1- and 2-year follow-ups, we performed an Intent-to-Treat (ITT) analysis. RESULTS: After 2 years from baseline, 48.4% of intervention group children showed a low-risk CHBS in comparison with 28.0% of control group children. A multilevel analysis showed that they were by far more likely to achieve low-risk scores (adjusted OR: 3.41; 95% CI: 1.48-7.88; P=0.004). Our BMI outcomes showed no significant difference between groups. CONCLUSIONS: A multidimensional educational intervention, which consists of motivational interviews with parents and teacher-led learning experiences for children, improved preschool children's CHBS in the long term without influencing the outcomes of BMI z-score and BMI increase.In September 2012, OROGEL S.p.A., a company based in via Dismano 2600, I-47522, Cesena, Forlì Cesena, Italy, granted €10 000 in support of our educational intervention. This sponsor had no role in designing and conducting our study; collecting, managing, analysing and interpreting its data; and preparing, reviewing and approving our paper

Thyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases.

BACKGROUND: Subclinical thyroid dysfunction, defined as thyroid-stimulating hormone levels outside the reference range with normal free thyroxine levels in asymptomatic patients, is associated with alterations in cardiac hemodynamics. We used Mendelian randomization to assess the role of thyroid dysfunction for cardiovascular disease (CVD). METHODS: Single-nucleotide polymorphisms associated with thyroid function were identified from a genome-wide association meta-analysis in up to 72 167 individuals. Data for genetic associations with CVD were obtained from meta-analyses of genome-wide association studies of atrial fibrillation (n=537 409 individuals), coronary artery disease (n=184 305 individuals), and ischemic stroke (n=438 847) as well as from the UK Biobank (n=367 703 individuals). RESULTS: Genetically predicted thyroid-stimulating hormone levels and hyperthyroidism were statistically significantly associated with atrial fibrillation but no other CVDs at the Bonferroni-corrected level of significance ( P<7.8×10-4). The odds ratios of atrial fibrillation were 1.15 (95% CI, 1.11-1.19; P=2.4×10-14) per genetically predicted 1 SD decrease in thyroid-stimulating hormone levels and 1.05 (95% CI, 1.03-1.08; P=5.4×10-5) for genetic predisposition to hyperthyroidism. Genetically predicted free thyroxin levels were not statistically significantly associated with any CVD. CONCLUSIONS: This Mendelian randomization study supports evidence for a causal association of decreased thyroid-stimulating hormone levels in the direction of a mild form of hyperthyroidism with an increased risk of atrial fibrillation but no other CVDs

New Coumarin derivatives as cholinergic and cannabinoid system modulators

In the last years, the connection between the endocannabinoid system (eCS) and neuroprotection has been discovered, and evidence indicates that eCS signaling is involved in the regulation of cognitive processes and in the pathophysiology of Alzheimer’s disease (AD). Accordingly, pharmacotherapy targeting eCS could represent a valuable contribution in fighting a multifaceted disease such as AD, opening a new perspective for the development of active agents with multitarget potential. In this paper, a series of coumarin-based carbamic and amide derivatives were designed and synthesized as multipotent compounds acting on cholinergic system and eCS-related targets. Indeed, they were tested with appropriate enzymatic assays on acetyl and butyryl-cholinesterases and on fatty acid amide hydrolase (FAAH), and also evaluated as cannabinoid receptor (CB1 and CB2) ligands. Moreover, their ability to reduce the self-aggregation of beta amyloid protein (Aβ42) was assessed. Compounds 2 and 3, bearing a carbamate function, emerged as promising inhibitors of hAChE, hBuChE, FAAH and Aβ42 self-aggregation, albeit with moderate potencies, while the amide 6 also appears a promising CB1/CB2 receptors ligand. These data prove for the new compounds an encouraging multitarget profile, deserving further evaluation

A robust and efficient method for Mendelian randomization with hundreds of genetic variants

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Abstract: Mendelian randomization (MR) is an epidemiological technique that uses genetic variants to distinguish correlation from causation in observational data. The reliability of a MR investigation depends on the validity of the genetic variants as instrumental variables (IVs). We develop the contamination mixture method, a method for MR with two modalities. First, it identifies groups of genetic variants with similar causal estimates, which may represent distinct mechanisms by which the risk factor influences the outcome. Second, it performs MR robustly and efficiently in the presence of invalid IVs. Compared to other robust methods, it has the lowest mean squared error across a range of realistic scenarios. The method identifies 11 variants associated with increased high-density lipoprotein-cholesterol, decreased triglyceride levels, and decreased coronary heart disease risk that have the same directions of associations with various blood cell traits, suggesting a shared mechanism linking lipids and coronary heart disease risk mediated via platelet aggregation

The role of the residual stresses of the epoxy-aluminum interphase on the interfacial fracture toughness

When an epoxy-diamine system (DGEBA-IPDA) is applied onto aluminum alloy (5754) and cured, an interphase having chemical, physical, and mechanical properties quite different from those of the bulk polymer is created between the substrate and the part of the polymer having bulk properties. To get a better understanding of the role of the interphase on the interfacial fracture toughness either a tri-layer (bulk coating=interphase=substrate) or a bi-layer model (bulk coating=substrate) were used for quantitative determination of the critical strain energy release rate (noted Gc). Indeed, as the interphase formation results from both dissolution and diffusion phenomena, we were able to control the interphase formation within coated systems by controlling the liquid-solid contact time and then to make tri- or bi-layered systems. The particularity of models used is to consider residual stress profiles developed within the entire system leading to an intrinsic parameter representing the work of adhesion between the polymer and the metallic substrate. The aim of this publication is to clearly establish the role of the interphase mechanical properties, such as Young's modulus and residual stress on the interfacial fracture toughness. Results are presented and discussed for three different aluminum surface treatments (chemical etching, degreasing and anodizing)

A School-Based Program to Promote Well-Being in Preadolescents: Results From a Cluster Quasi-Experimental Controlled Study

Diario della Salute [My Health Diary] is a school-based program designed to enhance the subjective well-being and health of 12- to 13-year-old students. We hypothesized that providing students with the social and emotional skills to fulfill their potential and deal with common developmental tasks of adolescence (e.g., onset of puberty, identity development, increased responsibilities and academic demands) would result in improved well-being and health. The program comprises five standardized interactive lessons concerning common psychosocial and health issues in adolescence, and two narrative booklets addressed to both students and their parents. We evaluated the effectiveness of the program in terms of the students' subjective well-being, aggressive behavior, and health behavior. Using a quasi-experimental study design, schools in the intervention group implemented the full program and those in the comparison group received their regular curriculum. We administered measures of the study's objectives both before and after program implementation. Statistical analyses accounted for within-school clustering, potential socioeconomic and demographic confounding, and pre-implementation levels of these measures. We sampled 62 schools and allocated 2630 students to either an intervention or comparison group. Sociodemographic characteristics and baseline outcomes were balanced across study groups. Unexpectedly, respondents in the intervention group had 0.38 greater mean adjusted score of the WHO/Europe Health Behaviour in School-Aged Children Symptom Checklist instrument than respondents in the comparison group, indicating a reduction in subjective well-being. We did not observe any program effects on aggressive and health behaviors. The apparent reduction in subjective well-being reflected by an increased perception of psychosomatic complaints is suggestive of either increased emotional competence or, potentially, iatrogenic program effects. While greater emotional competence is positively associated with well-being over the course of life, the program in its present form should not be disseminated due to the possibility of adverse unintended effects

Functional immune characterization of HIV-associated non-small-cell lung cancer.

Dear Editor, In the combined anti-retroviral therapy (cART) era, non-small cell lung cancer (NSCLC) is a highly incident cause of morbidity and mortality in people living with HIV (PLHIV)[1]. The immune-pathogenesis of NSCLC and HIV infection both rely on programmed-death 1 (PD-1) receptor-ligand interaction as a mechanism to induce T-cell exhaustion. To date, PLHIV have been excluded from clinical trials of immune-checkpoint inhibitors (ICPI), on the presumption that anti-tumour immunity might be compromised by HIV infection. To verify this, we evaluated the clinico-pathologic significance of PD-ligands expression in a consecutive series of 221 archival NSCLC samples, 24 of which were HIV-associated (Table S1)

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. AIM: To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. METHODS: Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. RESULTS: A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). CONCLUSIONS: In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC

Association of shorter leucocyte telomere length with risk of frailty.

BACKGROUND: Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty. METHODS: We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal. RESULTS: Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10-33 ), more likely to be female (61%, P = 1.97 × 10-129 ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10-111 ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10-12 ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10-30 ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13). CONCLUSIONS: Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.This research has been conducted using the UK Biobank Resource under Application Number 6077. Generation of the LTL measurements was funded by the UK Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council and British Heart Foundation (BHF) through MRC grant MR/M012816/1