Changes in and the mediating role of physical activity in relation to active school transport, fitness and adiposity among Spanish youth: the UP&DOWN longitudinal study

Background Longitudinal changes in child and adolescent active school transport (AST), and the mediating role of different intensities of daily physical activity (PA) levels in relation to AST and physical fitness and adiposity indicators is unclear. This study aimed to: 1) describe longitudinal changes in AST, light PA (LPA), moderate- to vigorous-intensity PA (MVPA), physical fitness and adiposity indicators over three time-points; and 2) investigate the mediating role of LPA and MVPA levels on associations between AST and physical fitness and adiposity indicators over three time-points among children and adolescents. Methods This longitudinal study comprised 1646 Spanish children and adolescents (48.8% girls, mean age 12.5 years +/- 2.5) at baseline, recruited from schools in Cadiz and Madrid. Mode of commuting to school was self-reported at baseline (T0, 2011-12), 1-year (T1) and 2-year follow-up (T2). PA was assessed using accelerometers. Handgrip strength, standing long jump and cardiorespiratory fitness (CRF) assessed physical fitness. Height, weight, body mass index, waist circumference, and triceps and subscapular skinfold thickness were measured. Multilevel linear regression analyses assessed changes in AST, PA levels, physical fitness and adiposity indicators over three time-points (T0-T1-T2). Additionally, longitudinal path analysis (n = 453; mean age [years] 12.6 +/- 2.4) was used to test the mediating effects of LPA and MVPA levels on the association between AST and physical fitness and adiposity indicators. Results Multilevel analyses observed decreases in LPA between T0-T1 (beta = - 11.27; p < 0.001) and T0-T2 (beta = - 16.27; p < 0.001) and decreases in MVPA between T0-T2 (beta = - 4.51; p = 0.011). Moreover, changes over time showed increases in handgrip between T0-T1 (beta = 0.78; p = 0.028) and T0-T2 (beta = 0.81; p = 0.046). Path analyses showed that AST was directly positively associated with MVPA at T1 (all, beta approximate to 0.33; p < 0.001). MVPA at T1 mediated associations between AST and CRF at T2 (beta = 0.20; p = 0.040), but not the other outcomes. LPA did not mediate any associations. Conclusions Results from longitudinal path analysis suggest that participation in more AST may help attenuate declines in MVPA that typically occur with age and improve CRF. Therefore, we encourage health authorities to promote AST, as a way to increase MVPA levels and CRF among youth

Health-related quality of life in KEYNOTE-010 : a phase II/III study of pembrolizumab versus docetaxel in patients with previously treated advanced, programmed death ligand 1-expressing NSCLC

Introduction: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score >= 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here. Methods: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m(2) every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain. Results: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had "deteriorated" status and more had "improved" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose. Conclusions: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

DYNAMICS OF THE Manilkara huberi (DUCKE) A. CHEV. POPULATION DURING 26 YEARS AFTER LOGGING IN A TERRA FIRME FOREST IN THE BRAZILIAN AMAZONIA

Changes in the structure of Manilkara huberi population in a 64 ha area at the Tapajos National Forest were evaluated in a 26-year period after logging. Data were obtained in 36 50m x 50m permanent sample plots that were assessed in eight occasions from 1981 to 2007, after the timber harvest, considering trees with DBH (diameter at 1,30m above the ground) 655cm. Density, frequency, basal area and importance value index of the species in the eight occasions were calculated. Diameter distribution of Manilkara huberi four years before logging was compared to diameter distribution 28 years after logging. Manilkara huberi population was lightly dynamic on abundance, frequency and basal area in the study area during the 26-year period after logging, indicating the need of a special and suitable management and silvicultural treatments to boost its natural regeneration and the growth of the young trees. Basal area of the species is growing very slowly indicating that it will probably need more than one hundred years to recover the initial stock.Foram avaliadas as mudan\ue7as ocorridas na estrutura da popula\ue7\ue3o de Manilkara huberi (Ducke) A. Chev. em uma \ue1rea de 64 ha na Floresta Nacional do Tapaj\uf3s, em um per\uedodo de 26 anos ap\uf3s a explora\ue7\ue3o. Os dados foram obtidos em 36 parcelas permanentes de 50 m x 50 m, que foram medidas em oito ocasi\uf5es, de 1981 a 2007, ap\uf3s a colheita da madeira, considerando os indiv\uedduos com DAP (di\ue2metro a 1,30 m do solo) 655 cm. Foi calculada a densidade, frequ\ueancia, domin\ue2ncia e \uedndice de valor de import\ue2ncia da esp\ue9cie nas oito ocasi\uf5es. Comparou-se a distribui\ue7\ue3o diam\ue9trica dos indiv\uedduos de Manilkara huberi aos quatro anos antes da explora\ue7\ue3o com a distribui\ue7\ue3o aos 28 anos ap\uf3s a explora\ue7\ue3o. A popula\ue7\ue3o de Manilkara huberi foi pouco din\ue2mica em densidade, frequ\ueancia e domin\ue2ncia, no per\uedodo de 26 anos ap\uf3s a explora\ue7\ue3o, indicando que necessita de manejo espec\uedfico e da aplica\ue7\ue3o de tratamentos silviculturais que venham a promover o aumento da sua regenera\ue7\ue3o natural na floresta e o crescimento das plantas mais jovens. A reposi\ue7\ue3o da \ue1rea basal da esp\ue9cie \ue9 muito lenta, indicando que vai precisar de, provavelmente, mais de cem anos para recuperar seu estoque inicial, considerando a intensidade de explora\ue7\ue3o aplicada

Diffusion microscopic MRI of the mouse embryo: Protocol and practical implementation in the splotch mouse model

Advanced methodologies for visualizing novel tissue contrast are essential for phenotyping the ever-increasing number of mutant mouse embryos being generated. Although diffusion microscopic MRI (μMRI) has been used to phenotype embryos, widespread routine use is limited by extended scanning times, and there is no established experimental procedure ensuring optimal data acquisition

ACCURACY OF OPTICAL DENDROMETERS FOR DETERMINING THE VOLUME OF STANDING TREES

O objetivo desse trabalho \ue9 verificar a exatid\ue3o dos dendr\uf4metros \uf3pticos Criterion 400 e RC3H, estudando a qualidade das medidas de cubagem da \ue1rvore em p\ue9 pelo uso desses dendr\uf4metros. O trabalho foi desenvolvido na Esta\ue7\ue3o Experimental de Itatinga - SP que pertence \ue0 Universidade de S\ue3o Paulo (ESALQUSP). Amostraram-se no total 175 \ue1rvores em tr\ueas parcelas de Eucalyptus grandis . O di\ue2metro do fuste das \ue1rvores em p\ue9 foi mensurado com os dois dendr\uf4metros \uf3pticos nas dist\ue2ncias de 0,1; 0,4; 0,7; 1,0; 1,3; 2,0 m e a partir desse ponto, de metro em metro ao longo do tronco at\ue9 os 8 m de altura. Ap\uf3s a cubagem em p\ue9 foram derrubadas as \ue1rvores e obtido o di\ue2metro nas diferentes posi\ue7\uf5es com uma suta e trena nas mesmas posi\ue7\uf5es em que se realizou a cubagem n\ue3o destrutiva. De posse dos di\ue2metros foi calculado o volume por sec\ue7\ue3o e por \ue1rvore individual pelo uso da f\uf3rmula de Smalian para posterior compara\ue7\ue3o dos m\ue9todos. Analisando as medidas do di\ue2metro do fuste e volume por \ue1rvore percebe-se que os dois dendr\uf4metros forneceram medidas subestimadas de modo geral, por\ue9m, o Criterion foi o que resultou nas melhores estimativas. Para o di\ue2metro e volume por \ue1rvore, o Criterion demonstrou erros subestimados m\ue9dios de aproximadamente 1 cm (10%), enquanto o RC3H resultou em erros superiores aos 5 cm (30%) em m\ue9dia. Portanto, quando se deseja maior confiabilidade e exatid\ue3o das vari\ue1veis observadas de forma n\ue3o destrutiva, o Criterion apresentou melhores resultados.The aim of this paper is to verify the accuracy of the optical dendrometers Criterion 400 and RC3H by studying the quality of measures of wood volume determination of standing trees through these dendrometers. The study was developed at the Experimental Station of Forest Sciences, in Itatinga, S\ue3o Paulo state, which belongs to the University of S\ue3o Paulo (ESALQ / USP). It was sampled a total of 175 trees in three plots of Eucalyptus grandis . The stem diameter of standing trees was measured by the two optical dendrometers at distances of 0.1, 0.4, 0.7, 1.0, 1.3, 2.0 meters from this point meter by meter along the stem up to 8 meters height. After measuring the standing trees they were felled and the diameter was obtained in different positions with a caliper and a tape in the same positions that the non-destructive measures were taken. With the diameters the volume was calculated by section and by individual trees by the Smalian formula for the comparison of methods. Analyzing the measurements of stem diameter and the individual tree volume realizes that the two dendrometers provided measures generally underestimated. However, the Criterion provided the best estimates. For the diameter and individual tree volume the Criterion showed underestimated errors averaging approximately 1 cm (10%), while the RC3H resulted in errors greater than 5 cm (30%) on average.Thus, when measuring observed variables in a non-destructive way with reliability and accuracy, the Criterion showed better results

IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents.

Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1 genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson?s chi-square or Fisher?s exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARG rs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these allele

Pathogenic p62/SQSTM1 mutations impair energy metabolism through limitation of mitochondrial substrates

Abnormal mitochondrial function has been found in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported in both disorders supporting the idea of an ALS/FTD continuum. In this work the role of p62 in energy metabolism was studied in fibroblasts from FTD patients carrying two independent pathogenic mutations in the p62 gene, and in a p62-knock-down (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y). We found that p62 deficiency is associated with inhibited complex I mitochondrial respiration due to lack of NADH for the electron transport chain. This deficiency was also associated with increased levels of NADPH reflecting a higher activation of pentose phosphate pathway as this is accompanied with higher cytosolic reduced glutathione (GSH) levels. Complex I inhibition resulted in lower mitochondrial membrane potential and higher cytosolic ROS production. Pharmacological activation of transcription factor Nrf2 increased mitochondrial NADH levels and restored mitochondrial membrane potential in p62-deficient cells. Our results suggest that the phenotype is caused by a loss-of-function effect, because similar alterations were found both in the mutant fibroblasts and the p62 KD model. These findings highlight the implication of energy metabolism in pathophysiological events associated with p62 deficiency

Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD