Autonomic thermoregulatory dysfunction in neurofibromatosis type 1 Disfunção autonômica termorregulatória na neurofibromatose do tipo 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, caused by mutations in a single gene (OMIM #162200, neurofibromin, 17 q11.2) affecting the development-maintenance-repair of neural and cutaneous tissues. Neurofibromatosis type 1 is the most common human monogenetic disease (1:3000, affecting nearly 80,000 Brazilian people) and it exhibits marked phenotype expression variability and an unpredictable course 5 , and both features are related to life expectancy, and quality of life. Possible mechanisms involving NF1-reduced muscle strength and aerobic capacity could be neurological abnormalities related to the neurofibromin deficiency, such as poorer motor coordination/activation, as well as lower levels of daily physical activities and motivation for exercising. Both neural disorder and reduced aerobic capacity could adversely affect thermoregulatory capacity, leading to decreased exercise performance in hot environments and heat intolerance with higher risk for heat-related injuries 6 . Despite increases in environmental temperature and/or exercise body metabolism, human internal temperature must be maintained within a small physiological range through heat dissipation, to prevent tissue ABSTRACT Objective: Neurofibromatosis type 1 (NF1) causes neural and cutaneous disorders and reduced exercise capacity. Exercise/heat exposure increasing internal temperature must be compensated by eccrine sweat function and warmed skin vasodilation. We suspected NF1 could adversely affect eccrine sweat function and/or vascular thermoregulatory responses (VTR). Methods: The eccrine sweat function and VTR of 25 NF1 volunteers (14 males, 11 females; 16-57 years old) were compared with 23 non-NF1 controls matched by sex, age, height and weight (CG). Sweating was induced by 1) pilocarpine 1% iontophoresis (PILO); and 2) by passive heating (HEAT) via the lower third of the legs being immersed in 42°C water for one hour. Previously established eccrine sweat function and VTR protocols were used. Results: The NF1 group showed: a) lower sweat rate than the CG group during PILO; b) a smaller diastolic pressure decrease; and c) higher tympanic temperatures than controls during HEAT (p < 0.05). Conclusion: Reduced sweating and vascular thermoregulatory responses suggest autonomic dysfunction in NF1 individuals. Keywords: neurofibromatosis 1; sweating; primary dysautonomias; body temperature regulation. RESUMO Objetivo: Neurofibromatose do tipo 1 (NF1) causa problemas neurais e cutâneos e diminuição da capacidade física. O aumento da temperatura interna durante exercício e exposição ao calor precisa ser compensada pela função sudorípara écrina (FSE) e aquecimento cutâneo por vasodilatação (RVT). Suspeitou-se clinicamente que a NF1 poderia prejudicar a FSE e a RVT. Métodos: A FSE e RVT de 25 voluntários com NF1 (14 homens, 11 mulheres; 16-57 anos) e de 23 sem-NF1, emparelhados por sexo, idade, estatura e peso corporal, foram medidas com protocolos validados anteriormente. A sudorese foi induzida por iontoforese com pilocarpina (PILO) e aquecimento passivo por imersão das pernas em água a 42°C durante uma hora (HEAT). Resultados: O grupo NF1 apresentou menor taxa de sudorese na situação PILO, menor redução da pressão diastólica e maior temperatura timpânica na situação HEAT (p < 0.05). Conclusão: As respostas sudorípara e vascular reduzidas sugerem disfunção autonômica nas pessoas com NF1. Palavras-chave: neurofibromatose 1; sudorese; disautonomia primária; regulação da temperatura corporal

Association of objective sedentary behaviour and self-rated health in English older adults

Abstract Objective Reducing sedentary behaviour (SB) might improve the health of older adults. However, we know little about how objectively measured SB impacts on self-rated health in older adults. We aimed to explore the associations between objectively measured SB and self-rated health in English older adults. Results A random sub-sample of older adults (≥ 65 years old) from the 2008 Health Survey for England wore an ActiGraph GT1M accelerometer for 7 days. Self-rated health was measured using an item from the General Health Questionnaire. Linear regression and analysis of covariance were used to test the associations between percentage time spent in SB and mean daily minutes in SB and self-rated health (very good/good; fair; bad/very bad), adjusting for covariates. Valid accelerometry datasets were returned by 578 individuals. Significant negative associations between percentage time and mean daily minutes in SB and self-rated health were found. In particular, individuals spending reduced percentages of time being sedentary had higher self-rated health. In conclusion, SB appears to be associated with self-rated health in older people independently from MVPA. If longitudinal research could determine how changes in SB influence self-rated health as individuals’ age, this might be an important lifestyle variable to target for health improvement

Socio-demographic, behavioural and cognitive correlates of work-related sitting time in German men and women

Background: Sitting time is ubiquitous for most adults in developed countries and is most prevalent in three domains: in the workplace, during transport and during leisure time. The correlates of prolonged sitting time in workplace settings are not well understood. Therefore, the aim of this study was to examine the gender-specific associations between the socio-demographic, behavioural and cognitive correlates of work-related sitting time. Methods: A cross-sectional sample of working German adults (n = 1515; 747 men; 43.5 ± 11.0 years) completed questionnaires regarding domain-specific sitting times and physical activity (PA) and answered statements concerning beliefs about sitting. To identify gender-specific correlates of work-related sitting time, we used a series of linear regressions. Results The overall median was 2 hours of work-related sitting time/day. Regression analyses showed for men (β = -.43) and for women (β = -.32) that work-related PA was negatively associated with work-related sitting time, but leisure-related PA was not a significant correlate. For women only, transport-related PA (β = -.07) was a negative correlate of work-related sitting time, suggesting increased sitting times during work with decreased PA in transport. Education and income levels were positively associated, and in women only, age (β = -.14) had a negative correlation with work-related sitting time. For both genders, TV-related sitting time was negatively associated with work-related sitting time. The only association with cognitive correlates was found in men for the belief ‘Sitting for long periods does not matter to me’ (β = .10) expressing a more positive attitude towards sitting with increasing sitting durations. Conclusions: The present findings show that in particular, higher educated men and women as well as young women are high-risk groups to target for reducing prolonged work-related sitting time. In addition, our findings propose considering increasing transport-related PA, especially in women, as well as promoting recreation-related PA in conjunction with efforts to reduce long work-related sitting times

Variation in population levels of sedentary time in European children and adolescents according to cross-European studies: a systematic literature review within DEDIPAC

peer-reviewedBackground: A high amount of sedentary time has been proposed as a risk factor for various health outcomes in adults. While the evidence is less clear in children and adolescents, monitoring sedentary time is important to understand the prevalence rates and how this behaviour varies over time and by place. This systematic literature review aims to provide an overview of existing cross-European studies on sedentary time in children (0-12y) and adolescents (13-18y), to describe the variation in population levels of sedentary time, and to discuss the impact of assessment methods. Methods: Six literature databases were searched (PubMed, EMBASE, CINAHL, PsycINFO, SportDiscus and OpenGrey), followed by backward- and forward tracking and searching authors’ and experts’ literature databases. Included articles were observational studies reporting on levels of sedentary time in the general population of children and/or adolescents in at least two European countries. Population levels were reported separately for children and adolescents. Data were reviewed, extracted and assessed by two researchers, with disagreements being resolved by a third researcher. The review protocol is published under registration number CRD42014013379 in the PROSPERO database. Forty-two eligible articles were identified, most were cross-sectional (n = 38). The number of included European countries per article ranged from 2 to 36. Levels of sedentary time were observed to be higher in East-European countries compared to the rest of Europe. There was a large variation in assessment methods and reported outcome variables. The majority of articles used a child-specific questionnaire (60 %). Other methods included accelerometers, parental questionnaires or interviews and ecological momentary assessment tools. Television time was reported as outcome variable in 57 % of included articles (ranging from a mean value of 1 h to 2.7 h in children and 1.3 h to 4.4 h in adolescents), total sedentary time in 24 % (ranging from a mean value of 192 min to 552 min in children and from 268 min to 506 min in adolescents). A substantial number of published studies report on levels of sedentary time in children and adolescents across European countries, but there was a large variation in assessment methods. Questionnaires (child specific) were used most often, but they mostly measured specific screen-based activities and did not assess total sedentary time. There is a need for harmonisation and standardisation of objective and subjective methods to assess sedentary time in children and adolescents to enable comparison across countries

A three arm cluster randomised controlled trial to test the effectiveness and cost-effectiveness of the SMART work & life intervention for reducing daily sitting time in office workers : study protocol

Background:Office-based workers typically spend 70-85% of working hours, and a large proportion of leisure time, sitting. High levels of sitting have been linked to poor health. There is a need for fully powered randomised controlled trials (RCTs) with long-term follow-up to test the effectiveness of interventions to reduce sitting. This paper describes the methodology of a three-arm cluster RCT designed to determine the effectiveness and cost-effectiveness of the SMART Work & Life intervention, delivered with and without a height-adjustable desk, for reducing daily sitting. Methods/Design:A three-arm cluster RCT of 33 clusters (660 council workers) will be conducted in three areas in England (Leicester; Manchester; Liverpool). Office groups (clusters) will be randomised to the SMART Work & Life intervention delivered with (group 1) or without (group 2) a height-adjustable desk or a control group (group 3). SMART Work & Life includes organisational (e.g., management buy-in, provision/support for standing meetings), environmental (e.g., relocating waste bins, printers), and group/individual (education, action planning, goal setting, addressing barriers, coaching, self-monitoring, social support) level behaviour change strategies, with strategies driven by workplace champions. Baseline, 3, 12 and 24 month measures will be taken. Objectively measured daily sitting time (activPAL3). objectively measured sitting, standing, stepping, prolonged sitting and moderate-to-vigorous physical activity time and number of steps at work and daily; objectively measured sleep (wrist accelerometry). Adiposity, blood pressure, fasting glucose, glycated haemoglobin, cholesterol (total, HDL, LDL) and triglycerides will be assessed from capillary blood samples. Questionnaires will examine dietary intake, fatigue, musculoskeletal issues, job performance and satisfaction, work engagement, occupational and general fatigue, stress, presenteeism, anxiety and depression and sickness absence (organisational records). Quality of life and resources used (e.g. GP visits, outpatient attendances) will also be assessed. We will conduct a full process evaluation and cost-effectiveness analysis. Discussion:The results of this RCT will 1) help to understand how effective an important simple, yet relatively expensive environmental change is for reducing sitting, 2) provide evidence on changing behaviour across all waking hours, and 3) provide evidence for policy guidelines around population and workplace health and well-being. Trial registration: ISRCTN11618007 . Registered on 21 January 2018

Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies

Abstract\ud \ud Background\ud Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere. Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments. While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform “community-level” metabolism of lignocellulose. Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.\ud \ud \ud Results\ud Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost. Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks. Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment. Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera. The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance. A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant. This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation. The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.\ud \ud \ud Conclusions\ud A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks. In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.This work was funded by Biotechnology and Biological Sciences Research\ud Council (BBSRC) Grants BB/1018492/1, BB/K020358/1 and BB/P027717/1, the\ud BBSRC Network in Biotechnology and Bioenergy BIOCATNET and São Paulo\ud Research Foundation (FAPESP) Grant 10/52362-5. ERdA thanks EMBRAPA\ud Instrumentation São Carlos and Dr. Luiz Alberto Colnago for providing the\ud NMR facility and CNPq Grant 312852/2014-2. The authors would like to thank\ud Deborah Rathbone and Susan Heywood from the Biorenewables Develop‑\ud ment Centre for technical assistance in rRNA amplicon sequencing