Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Ciprofloxacin, diclofenac, ibuprofen and 17α-ethinylestradiol differentially affect the activity of acetogens and methanogens in anaerobic communities

Pharmaceutical compounds end up in wastewater treatment plants but little is known on their effect towards the different microbial groups in anaerobic communities. In this work, the effect of the antibiotic Ciprooxacin (CIP), the non-steroidal anti-inammatory drugs Diclofenac (DCF) and Ibuprofen (IBP), and the hormone 17-ethinylestradiol (EE2), on the activity of acetogens and methanogens in anaerobic communities, was investigated. Microbial communities were more affected by CIP, followed by EE2, DCF and IBP, but the response of the different microbial groups was dissimilar. For concentrations of 0.01 to 0.1 mg/L, the specic methanogenic activity was not affected. Acetogenic bacteria were sensitive to CIP concentrations above 1 mg/L, while DCF and EE2 toxicity was only detected for concentrations higher than 10 mg/L, and IBP had no effect in all concentrations tested. Acetoclastic methanogens showed higher sensitivity to the presence of these micropollutants, being affect by all the tested pharmaceutical compounds although at different degrees. Hydrogenotrophic methanogens were not affected by any concentration, indicating their lower sensitivity to these compounds when compared to acetoclasts and acetogens.e Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Ana Rita Silva holds a Grant from FCT, reference SFRH/BD/131905/2017info:eu-repo/semantics/publishedVersio

Genetic Diversity and Population Structure of Saccharomyces cerevisiae Strains Isolated from Different Grape Varieties and Winemaking Regions

We herein evaluate intraspecific genetic diversity of fermentative vineyard-associated S. cerevisiae strains and evaluate relationships between grape varieties and geographical location on populational structures. From the musts obtained from 288 grape samples, collected from two wine regions (16 vineyards, nine grape varieties), 94 spontaneous fermentations were concluded and 2820 yeast isolates were obtained that belonged mainly (92%) to the species S. cerevisiae. Isolates were classified in 321 strains by the use of ten microsatellite markers. A high strain diversity (8–43 strains per fermentation) was associated with high percentage (60–100%) of fermenting samples per vineyard, whereas a lower percentage of spontaneous fermentations (0–40%) corresponded to a rather low strain diversity (1–10 strains per fermentation)

A comparison of multidisciplinary team residential rehabilitation with conventional outpatient care for the treatment of non-arthritic intra-articular hip pain in UK Military personnel:a protocol for a randomised controlled trial

BACKGROUND: Non-arthritic hip disorders are defined as abnormalities of the articulating surfaces of the acetabulum and femur before the onset of osteoarthritis, including intra-articular structures such as the acetabular labrum and chondral surfaces. Abnormal femoroacetabular morphology is commonly seen in young men who constitute much of the UK military population. Residential multidisciplinary team (MDT) rehabilitation for patients with musculoskeletal injuries has a long tradition in the UK military, however, there are no studies presenting empirical data on the efficacy of a residential MDT approach compared with individualised conventional outpatient treatment. With no available data, the sustainability of this care pathway has been questioned. The purpose of this randomised controlled trial is to compare the effects of a residential multidisciplinary intervention, to usual outpatient care, on the clinical outcomes of young active adults undergoing treatment for non-arthritic intra-articular hip pain. METHODS/DESIGN: The trial will be conducted at the Defence Medical Rehabilitation Centre, Headley Court, UK. One hundred military male participants with clinical indicators of non-arthritic intra-articular hip pain will be randomly allocated to either: (1) 7-day residential multidisciplinary team intervention, n = 50; (2) 6-week physiotherapist-led outpatient intervention (conventional care), n = 50. Measurements will be taken at baseline, post-treatment (1-week MDT group; 6-weeks physiotherapy group), and 12-weeks. The primary outcome measures are the function in daily living sub-scale of the Copenhagen Hip and Groin Outcome Score (HAGOS), the physical function subscale of the Non-arthritic Hip Score (NAHS), and VAS pain scale. Secondary outcomes include objective measures of physical capacity and general health. An intention-to-treat analysis will be performed using linear and mixed models. DISCUSSION: This study will be the first to assess the efficacy of intensive MDT rehabilitation, versus conventional outpatient care, for the management of non-arthritic hip pain. The results from this study will add to the evidence-base and inform clinical practice for the management of intra-articular non-arthritic hip pain and femoroacetabular impingement in young active adults. TRIAL REGISTRATION: ISRCTN Reference: ISRCTN 59255714 dated 11-Nov-2015 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-016-1309-z) contains supplementary material, which is available to authorized users

Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance. Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF

Methods used to evaluate the en dehors or turnout of dancers and classical ballet dancers: a literature review

A técnica do ballet clássico exige a realização máxima do en dehors ou turnout, caracterizado pela rotação externa de membros inferiores. Considerando a sua importância, diversos protocolos para a sua avaliação e mensuração têm sido propostos. O objetivo desta revisão foi investigar sistematicamente quais os métodos utilizados para avaliar o turnout de bailarinos clássicos e/ou praticantes de ballet clássico existentes atualmente. A busca foi feita nas bases de dados Scopus, Science Direct e PubMed, no mês de fevereiro de 2016, e os artigos encontrados deveriam: estar redigidos na língua inglesa, avaliar bailarinos clássicos ou dançarinos que praticassem ballet clássico e mensurar o en dehors ou turnout. Foram encontrados 593 artigos, dos quais 25 foram pré-selecionados para esta revisão, apresentando quinze diferentes métodos e instrumentos de mensuração do turnout: cinemetria; inclinômetro; turnout protactor ou transferidor para medir o turnout; goniômetro; Dupuis Tropometer; transferidor original; fotos dos sujeitos; discos rotacionais; teste de flexibilidade de Nicholas; flexímetro; desenho clínico dos pés; sujeito sobre um pedaço de papel ou solo ou quadro branco; ressonância magnética; filmagem do sujeito executando sequência de passos; Dasco Pro Angle Finder. Esta revisão apresenta forte evidência para afirmar que não há, até o presente momento, um método ou instrumento padrão-ouro para mensuração do turnout de bailarinos, de modo que esta costuma ser adaptada e escolhida de acordo com o objetivo de cada estudo.La técnica del ballet clásico exige la realización máxima del en dehors o turnout, caracterizado por la rotación externa de miembros inferiores. Considerando su importancia, varios protocolos para su evaluación y medición han sido propuestos. El objetivo de esta revisión ha sido investigar sistemáticamente los métodos utilizados para evaluar el turnout de bailarines clásicos y/o practicantes de ballet clásico existentes actualmente. Se hizo la búsqueda en las bases de datos Scopus, Science Direct y PubMed, en el mes de febrero de 2016, y los artículos encontrados deberían: estar redactados en la lengua inglesa, evaluar bailarines clásicos o bailarines que practicaran ballet clásico y medir el en dehors o turnout. Se encontraron 593 artículos, de los cuales se preseleccionaron 25 para esta revisión, presentándose 15 diferentes métodos e instrumentos de medición del turnout: cinemetría; inclinómetro; turnout protactor o transferidor para medir el turnout; goniómetro; Dupuis Tropometer; transferidor original; fotos de los sujetos; discos rotacionales; prueba de flexibilidad de Nicholas; flexímetro; diseño clínico de los pies; sujeto sobre un pedazo de papel o suelo o cuadro blanco; resonancia magnética; filmación del sujeto ejecutando secuencia de pasos; Daco Pro Angle Finder. Esta revisión presenta una fuerte evidencia para afirmar que no hay, hasta el momento, un método o instrumento estándar-oro para la medición del turnout de bailarines, de modo que ésta suele ser adaptada y elegida de acuerdo con el objetivo de cada estudio.The classical ballet technique requires the maximum en dehors or turnout, which is the lower limbs external rotation. Considering its importance, several evaluation and measurement protocols have been proposed. This review aims to investigate systematically which methods were used to assess the classical dancers’ or classical ballet practitioners’ turnout. A systematic search was made in the Scopus, Science Direct, and PubMed databases in February 2016 for studies written in English that evaluated classical dancers or ballerinas, and the en dehors or turnout was measured. We found 593 articles, of which 25 were pre-selected for this review, featuring fifteen different methods and instruments for measuring turnout: kinemetry; inclinometer; Turnout Protractor, or protractor to measure the turnout; goniometer; dupuis tropometer; original protractor; subjects photos; rotational discs; Nicholas flexibility test; fleximeter; clinical drawing of the feet; subject standing on a piece of paper, or soil, or whiteboard; magnetic resonance; filming the subject during a sequence of dance steps; Dasco pro angle finder. This review rovides convincing evidence that there is not a method or gold-standard instrument for measuring dancers’ turnout, therefore such measurement is usually adapted and chosen according to each study objectives

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project

Effects of transaldolase exchange on estimates of gluconeogenesis in type 2 diabetes

13 C]acetate during a separate visit in a subset of ND (n ϭ 7) subjects. Ratio of 13 C3/ 13 C4 obtained following either tracer was Ͻ1.0 at baseline and during clamp, indicating that TPI exchange was essentially complete and did not contribute to asymmetric glucose enrichment. Uncorrected and corrected rates of gluconeogenesis were no different (P ϭ not significant) in T2DM vs. ND both at baseline and during clamp. TA correction resulted in equivalent estimates of corrected gluconeogenesis in T2DM and ND that were ϳ25-35% lower than uncorrected gluconeogenesis both at baseline and during the clamp. The asymmetric enrichment of glucose from 13 C-gluconeogenic tracers is attributable to TA exchange and can be utilized to correct for TA exchange. In conclusion, TA exchange does not differ between T2DM and ND under fasting or hyperglycemic clamp conditions, and the 2 H2O method continues to provide an accurate estimation of gluconeogenesis. gluconeogenesis; deuterated water; transaldolase; triose phosphate isomerase AFTER AN OVERNIGHT FAST, plasma glucose is not symmetrically labeled from gluconeogenic carbon tracers such as [U- 13 C] glycerol (21) and [3-14 C]lactate (25). Exchange of fructose 6-phosphate and triose phosphate mediated by transaldolase has been implicated by us (3, 7, 9) and others (12) in overestimation of rates of gluconeogenesis, utilizing the deuterated water method. In this method, glucose derived from glycogenolysis (GGL) via glucose 6-phosphate (G6P) source can become labeled in carbons 4, 5, and 6 from either a carbonlabeled gluconeogenic precursor or deuterated water independent of gluconeogenesis. This results in an overestimation of the gluconeogenic fraction and a corresponding underestimation of the glycogenolytic contribution to endogenous glucose production. This exchange is particularly important in the study of type 2 diabetes mellitus (T2DM) since it mimics the characteristic shift toward increased hepatic gluconeogenic activity during the progression of this disease. With a few exceptions (14), stable isotope tracer studies indicate an increased fractional gluconeogenesis in overnight-fasted T2DM subjects compared with healthy nondiabetic (ND) controls 13 C]acetate infusion under conditions of fasting and during a hyperglycemic moderate-dose insulin clamp to determine whether or not TA exchange activity explains differences in glucose enrichment from gluconeogenic substrates between ND and T2DM subjects. We have demonstrated that TA activity occurs in healthy humans based on a higher enrichment of glucose carbon 4 over carbon 3 (i.e., C]acetate (3). In this study, the asymmetric labeling of glucose from this tracer could also be explained by incomplete exchange of the label between glyceraldehyde 3-phosphate and dihydroxyacetone phosphate mediated by incomplete triose phosphate isomerase (TPI; see Therefore, we also compared the 13 C enrichment of glucose from [1- 13 C]acetate and [U-13 C]glycerol in a subset of ND subjects to determine the extent to which asymmetric glucose C3 and C4 enrichments are determined by incomplete TPI exchange and by TA exchange