Crescimento, desempenho motor e cognitivo de crianças. Um estudo longitudinal-misto.

O propósito principal desta tese foi investigar, numa ótica contextual, as relações entre o crescimento físico, o desempenho motor e o desempenho cognitivo de crianças Portuguesas dos 4 aos 11 anos de idade.A amostra foi constituída por 411 crianças seguidas longitudinalmente durante 3 anos consecutivos e divididas em 6 coortes etárias. As crianças provêm das 19 escolas do Concelho de Vouzela, centro do país. Foram utilizados procedimentos estandardizados para medir marcadores do crescimento físico, composição corporal, coordenação motora grossa, aptidão física, preferência manual, atividade física, inteligência, da gestação, estatuto socioeconómico e espaços escolares. As análises estatísticas foram realizadas nos softwares SPSS, Supermix e STATA.Em termos genéricos, os resultados mostraram que: (1) no baseline as meninas têm maior quantidade de massa gorda; os meninos são mais coordenados, fisicamente aptos e ativos; ~60% das meninas não cumprem as recomendações diárias de atividade física moderada-a-vigorosa e a taxa de cumprimento dos meninos é de 74%; a maioria das escolas está localizada em áreas rurais; todas possuem playgrounds, e equipamentos para realizar atividades físicas; (2) as trajetórias do crescimento físico, no peso e no IMC, exibem uma tendência não-linear. O peso ao nascer, o comprimento ao nascer e os ganhos de peso e comprimento até os 18 meses explicaram diferenças nas trajetórias de crescimento físico; (3) as trajetórias do desenvolvimento coordenativo são não-lineares. IMC, a preferência manual e a aptidão física das crianças explicaram diferenças inter-individuais; as meninas tendem a ter um desenvolvimento coordenativo superior; (4) as trajetórias de desenvolvimento da aptidão física exibem uma tendência não-linear favorecendo os meninos; o peso ao nascer influencia a força e a agilidade, o IMC está negativamente associado à agilidade, porém positivamente associado à força; a coordenação motora grossa está associada à aptidão física; em contra partida, a atividade física moderada-a-vigorosa não esteve associada ao desenvolvimento da força estática; (5) as trajetórias de desenvolvimento da inteligência é linear, não há diferenças entre os sexos e a coordenação motora associou-se positivamente com tal desenvolvimento; (6) o estatuto socioeconómico e o contexto escolar não se associaram significativamente com o crescimento físico, coordenação motora grossa, aptidão física e inteligência de crianças Vouzelenses.Em suma, os resultados sublinharam a importância da abordagem multidisciplinar no estudo do crescimento e desenvolvimento de crianças, a relevância do delineamento longitudinal-misto e necessidade de uma vasta gama informacional. Ademais, é necessária a consideração de preditores fixos e dinâmicos para melhor interpretar de modo mais extenso as diferenças intra-individuais e entre crianças nas suas trajetórias de crescimento e desenvolvimento.The main purpose of this thesis was to investigate, in a contextual perspective, the relationships between physical growth and both motor, and cognitive performances of Portuguese children from 4 to 11 years old.The sample was comprised of 411 children from the 19 schools of Vouzela municipality, located at the center of the country, which were divided into 6 age cohorts and longitudinally followed for 3 consecutive years. Standardized procedures were used to measure indicators of physical growth, body composition, gross motor coordination, physical fitness, manual preference, physical activity, intelligence, gestation, socioeconomic status and school content. Statistical analyses were performed in SPSS, Supermix and STATA software.In general, results showed that: (1) at baseline, girls had more body fat mass; boys were more coordinated, physically fit and active; ~60% of girls did not meet the daily recommendations of moderate-to-vigorous physical activity, while the boys' were 74%; most of the schools were located in rural areas; all had playgrounds, and equipment for physical activity; (2) physical growth trajectories, both in weight and BMI, exhibited a non-linear trend. Birth weight, birth length, and gains on weight and length up to 18 months explained differences in physical growth trajectories; (3) coordinative development trajectories were non-linear. BMI, manual preference and physical fitness of children explained inter-individual differences; girls tended to have higher coordinative development; (4) physical fitness development trajectories exhibited a non-linear tendency favoring boys; birth weight influenced strength and agility, BMI was negatively associated with agility, but positively associated with strength; gross motor coordination was associated with physical fitness; in contrast, moderate-to-vigorous physical activity was not associated with the development of static force; (5) developmental trajectories of intelligence were linear, no differences between the sexes were found, and motor coordination was positively associated with such development; (6) socioeconomic status and school context were not significantly associated with physical growth, gross motor coordination, physical fitness, and intelligence of Vouzela children.In summary, these results showed the relevance of the multidisciplinary approach in the study of children's growth and development, the importance of the longitudinal-mixed design and the need for a wide informational range. In addition, it was necessary to consider fixed and dynamic predictors to better interpret intra-individual differences and between children in their growth and development trajectories more extensively.Key-words: physical growth, motor performance, cognitive performance, longitudinal design, children

Proficiency and manual asymmetry in young people with trisomy 21 in two manual dexterity tasks

Objectivo: Avaliar a proficiência e assimetria manual de indivíduos com Trissomia 21 (T21) em dois testes de destreza manual: global e fina. Métodos: Participaram 21 indivíduos com T21 entre os 17 e os 45 anos, sendo 13 destros, residentes na cidade do Porto, Portugal. Para a avaliação da Destreza Manual Global (DMG) utilizou-se o Minnesota Manual Dexterity Test (versão de colocação) e para a Destreza Manual Fina (DMF), o PurduePegboard. Resultados: No teste de DMF não se verificaram diferenças estatisticamente significativas (t(20)=1.23, p=0.233) entre as mãos; porém, no teste de DMG a diferença entre as mãos alcançou significado estatístico (t(20)=3.128, p=0,005), sendo a mão não preferida (145.22±53.42 seg.) mais rápida do que a mão preferida (156.16±59.99 seg.). O Índice de Assimetria Manual para cada uma das tarefas foi calculado, porém, não revelou significado estatístico (t(20)=-1.003, p=0.328). Conclusão: A melhor proficiência com a mão não preferida na tarefa de DMG pode estar relacionada com características peculiares para esta população, como as dificuldades na motricidade seletiva, o que empobreceria o desempenho para ambas as mãos, ou ainda com outros fatores a serem investigados. Os dados sugerem que tarefas de DMF e DMG desempenhadas por pessoas com T21 não são influenciadas pela preferência manual.Objective: To evaluate the proficiency and manual asymmetry of individuals with Trisomy 21 (T21) in two manual dexterity tests: global and fine. Methods: Participants were 21 individuals with T21 between 17 and 45 years, 13 right-handed, residents in the city of Porto, Portugal. For evaluating the overall handedness (DMG) we used the Minnesota Manual Dexterity Test (placement version) and for fine manual dexterity (DMF), the Purdue Pegboard.Results: In DMF test statistically significant differences were not observed (t (20) = 1.23, p = 0.233) between the hands, but in the DMG test the difference between hands reach statistical significance (t (20) = 3.128, p = 0.005), not being the preferred hand (145.22 sec ± 53.42) faster than the preferred hand (156.16 sec ± 59.99). The Asymmetry Index Manual for each task was conducted, however, did not reveal statistically significant (t (20) = - 1.003, p = 0.328). Conclusion: The best proficiency with the hand not preferred in DMG task may be related to peculiar characteristics to this population, such as difficulties in selective motor, which impoverish the performance for either hand, or with other factors to be investigated. The data suggest that the task performed by DMG and DMF and people with T21 are not influenced by manual preference.info:eu-repo/semantics/publishedVersio

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension