Lung CD57+ cell density is increased in very severe COPD

Among all inflammatory cells involved in COPD, those with a cytolytic or elastolytic activity are thought to play a key role in the pathogenesis of the disease. However, there is no data about the infiltration of cells expressing the CD57 marker in small airways and parenchyma of COPD patients. In this study, surgical specimens from 43 subjects undergoing lung resection due to lung cancer (9 non-smokers, 18 smokers without COPD and 16 smokers with moderate COPD) and 16 patients undergoing double lung transplantation for very severe COPD were examined. CD57+ cells, neutrophils, macrophages and mast cells infiltrating bronchioles (epithelium, smooth muscle and connective tissue) and parenchymal interstitium were localized and quantified by immunohistochemical analysis. Compared to the other groups, the small airways of very severe COPD patients showed a significantly higher density of CD57+ cells, mainly infiltrated in the connective tissue (p=0.001), and a significantly higher density of neutrophils located characteristically in the epithelium (p=0.037). Also, the density of neutrophils was significantly higher in parenchyma of very severe COPD patients compared with the rest of the groups (p=0.001). Finally, there were significant correlations between the bronchiolar density of CD57+ cells and the FEV1 values (R=-0.43, p=0.022), as well as between the parenchymal density of neutrophils and macroscopic emphysema degree (R=0.43, p=0.048) in COPD groups. These results show that CD57+ cells may be involved in COPD pathogenesis, especially in the most severe stages of the disease

Amerindian Ancestry Influences Genetic Susceptibility to Chronic Obstructive Pulmonary Disease

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5x10(-4)) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10(-3) to 3.77x10(-8)). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent

Healthy lifestyle behaviors and their association with self-regulation in chilean children

Indexación: Scopus.Background: Self-regulation comprises a series of important competencies, such as the ability to control inner states or responses toward thoughts, attention, emotions, or even performance. The relationship between self-regulation and different healthy lifestyle behaviors among children has not been examined in depth to date. The aim of this study was to explore the association between physical activity, screen time levels, and/or Mediterranean Diet adherence and self-regulation in Chilean children. Methods: A total of 1561 children aged 8–12 years from eight public schools with low socioeconomic status were included. Physical activity, screen time, Mediterranean Diet, and self-regulation were assessed with validated questionnaires. Results: Children who were classified as active or those who reported less than 2 h per day of screen time had higher self-regulation than those who were classified as inactive or counterparts with 2 h per day or more of screen time, respectively. Using joint categories, active children both with low and high screen time showed higher self-regulation compared to inactive/high screen time peers. Additionally, active groups with adherence or non-adherence to the Mediterranean Diet had higher self-regulation compared to inactive and non-adherence peers. Conclusion: Having a greater number of healthy habits, mainly regular physical activity, was associated with higher self-regulation, which might be one potential strategy to promote child social-emotional development. © 2020 by the authors.https://www.mdpi.com/1660-4601/17/16/567

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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Cardiorespiratory Fitness and Muscular Strength as Mediators of the Influence of Fatness on Academic Achievement

Objective To examine the combined association of fatness and physical fitness components (cardiorespiratory fitness [CRF] and muscular strength) with academic achievement, and to determine whether CRF and muscular strength are mediators of the association between fatness and academic achievement in a nationally representative sample of adolescents from Chile. Study design Data were obtained for a sample of 36 870 adolescents (mean age, 13.8 years; 55.2% boys) from the Chilean System for the Assessment of Educational Quality test for eighth grade in 2011, 2013, and 2014. Physical fitness tests included CRF (20-m shuttle run) and muscular strength (standing long jump). Weight, height, and waist circumference were assessed, and body mass index and waist circumference-to-height ratio were calculated. Academic achievement in language and mathematics was assessed using standardized tests. The PROCESS script developed by Hayes was used for mediation analysis. Results Compared with unfit and high-fatness adolescents, fit and low-fatness adolescents had significantly higher odds for attaining high academic achievement in language and mathematics. However, in language, unfit and low-fatness adolescents did not have significantly higher odds for obtaining high academic achievement. Those with high fatness had higher academic achievement (both language and mathematics) if they were fit. Linear regression models suggest a partial or full mediation of physical fitness in the association of fatness variables with academic achievement. Conclusions CRF and muscular strength may attenuate or even counteract the adverse influence of fatness on academic achievement in adolescents. © 2017 Elsevier Inc

Cardiorespiratory Fitness and Muscular Strength as Mediators of the Influence of Fatness on Academic Achievement

Objective To examine the combined association of fatness and physical fitness components (cardiorespiratory fitness [CRF] and muscular strength) with academic achievement, and to determine whether CRF and muscular strength are mediators of the association between fatness and academic achievement in a nationally representative sample of adolescents from Chile. Study design Data were obtained for a sample of 36 870 adolescents (mean age, 13.8 years; 55.2% boys) from the Chilean System for the Assessment of Educational Quality test for eighth grade in 2011, 2013, and 2014. Physical fitness tests included CRF (20-m shuttle run) and muscular strength (standing long jump). Weight, height, and waist circumference were assessed, and body mass index and waist circumference-to-height ratio were calculated. Academic achievement in language and mathematics was assessed using standardized tests. The PROCESS script developed by Hayes was used for mediation analysis. Results Compared with unfit and high-fatness adolescents, fit and low-fatness adolescents had significantly higher odds for attaining high academic achievement in language and mathematics. However, in language, unfit and low-fatness adolescents did not have significantly higher odds for obtaining high academic achievement. Those with high fatness had higher academic achievement (both language and mathematics) if they were fit. Linear regression models suggest a partial or full mediation of physical fitness in the association of fatness variables with academic achievement. Conclusions CRF and muscular strength may attenuate or even counteract the adverse influence of fatness on academic achievement in adolescents. © 2017 Elsevier Inc

Association analysis in a Latin American population revealed ethnic differences in rheumatoid arthritis-associated SNPs in Caucasian and Asian populations

Large genome-wide association studies (GWAS) have increased our knowledge of the genetic risk factors of rheumatoid arthritis (RA). However, little is known about genetic susceptibility in populations with a large admixture of Amerindian ancestry. The aim of the present study was to test the generalizability of previously reported RA loci in a Latin American (LA) population with admixed ancestry. We selected 128 single nucleotide polymorphisms (SNPs) in linkage equilibrium, with high association to RA in multiple populations of non-Amerindian origin. Genotyping of 118 SNPs was performed in 313 RA patients/487 healthy control subjects by mid-density arrays of polymerase chain reaction (PCR). Some of the identifed associations were validated in an additional cohort (250 cases/290 controls). One marker, the SNP rs2451258, located upstream of T Cell Activation RhoGTPase Activating Protein (TAGAP) gene, showed signifcant association with RA (p=5 × 10−3), whereas 18 markers exhibited suggestive associations (p<0.05). Haplotype testing showed association of some groups of adjacent SNPs around the signal transducer and activator of transcription 4 (STAT4) gene (p=9.82 × 10−3 to 2.04 × 10−3) with RA. Our major fnding was little replication of previously reported genetic associations with RA. These results suggest that performing GWAS and admixture mapping in LA populations has the potential to reveal novel loci associated with RA. This in turn might help to gain insight into the 'pathogenomics' of this disease and to explore trans-population diferences for RA in general

Review of the advances in treatment for Alzheimer disease: strategies for combating β-amyloid protein

Introduction: Alzheimer disease (AD) is a major neurodegenerative disorder which eventually results in total intellectual disability. The high global prevalence and the socioeconomic burden associated with the disease pose major challenges for public health in the 21st century. In this review we focus on both existing treatments and the therapies being developed, which principally target the β-amyloid protein. Discussion: The amyloidogenic hypothesis proposes that β-amyloid plays a key role in AD. Several pharmacological approaches aim to reduce the formation of β-amyloid peptides by inhibiting the β-secretase and γ-secretase enzymes. In addition, both passive and active immunotherapies have been developed for the purpose of inhibiting β-amyloid peptide aggregation. Conclusions: Progress in identifying the molecular basis of AD may provide better models for understanding the causes of this neurodegenerative disease. The lack of efficacy of solanezumab (a humanised monoclonal antibody that promotes β-amyloid clearance in the brain), demonstrated by 2 recent Phase III clinical trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs to be revised. Resumen: Introducción: La enfermedad de Alzheimer (EA) es el principal trastorno neurodegenerativo que provoca una discapacidad intelectual total en los pacientes que la presentan. La elevada prevalencia a nivel mundial, así como la elevada carga socioeconómica que conlleva la EA para la sociedad en general, hace que sea considerada un importante problema de salud pública en este siglo xxi. En este trabajo se revisan los tratamientos actuales y en fase de desarrollo que actúan principalmente sobre la proteína β-amiloide. Discusión: La hipótesis amiloidogénica propone que el péptido β-amiloide tiene un papel clave en esta enfermedad. Se han desarrollado varias estrategias farmacológicas diferentes con el objetivo de inhibir la formación de los péptidos β-amiloides, como son los inhibidores de β-secretasa y γ-secretasa. Además, se han desarrollado los tratamientos antiamiloide, que incluyen inmunoterapias pasivas y activas enfocadas a inhibir la agregación del péptido β-amiloide. Conclusiones: Los avances en la identificación de las bases moleculares de la EA pueden servir como modelo para comprender las causas de esta enfermedad neurodegenerativa. Sin embargo, los ensayos clínicos más recientes en 2 ensayos de fase iii con solanezumab, un anticuerpo monoclonal humanizado que promueve el aclaramiento del β-amiloide en el cerebro, indican que este anticuerpo no muestra eficacia en pacientes con EA leve, sugiriendo que hay que replantearse esta hipótesis amiloidogénica de la EA. Keywords: Alzheimer disease, Beta-amyloid, Beta-secretase, Gamma-secretase, Amyloid hypotheses, Palabras clave: Alzheimer, Beta-amiloide, Beta-secretasa, Gamma-secretasa, Hipótesis amiloide

Effects of exercise on carotid arterial wall thickness in obese pediatric populations: A meta-analysis of randomized controlled trials

Background: In pediatric populations, the use of carotid intima-media thickness (IMT) as a marker of cardiovascular risk has increased. However, previous studies examining the effects of exercise training on arterial structure and function in obese children and adolescents have shown inconsistent findings. The primary aim of this systematic review and meta-analysis is to expand on the current body of literature by providing a quantitative estimate of the change in carotid IMT following exercise training as well as to provide an exploratory analysis of potential moderators associated with the variation in response to an exercise training intervention in overweight and obese youth. Materials and Methods: A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on carotid IMT in pediatric obesity (6-18-year-olds). Hedges' g and 95% confidence intervals (CIs) were calculated. Results: Six randomized controlled trials (303 youths) were included. Exercise was associated with a small-to-moderate but significant reduction in carotid IMT (g = -0.306; 95% CI -0.540 to -0.072; p = 0.011). Likewise, exercise program duration per week significantly influenced the effect of exercise on carotid IMT (? = -0.060; p = 0.015). Conclusions: Exercise seems to reduce carotid IMT in childhood obesity. Therefore, encouraging obese pediatric individuals to become physically active can lead to favorable changes in the arterial wall. © Copyright 2017, Mary Ann Liebert, Inc