Topologically-constrained fluctuations and thermodynamics regulate nonequilibrium response

Limits on a system's response to external perturbations inform our understanding of how physical properties can be shaped by microscopic characteristics. Here, we derive constraints on the steady-state nonequilibrium response of physical observables in terms of the topology of the microscopic state space and the strength of thermodynamic driving. Notably, evaluation of these limits requires no kinetic information beyond the state-space structure. When applied to models of receptor binding, we find that sensitivity is bounded by the steepness of a Hill function with a Hill coefficient enhanced by the chemical driving beyond the structural equilibrium limit.Comment: 25 pages, 13 figure

Do the torso muscles produce torso twist in front crawl?

The purpose of this study was to investigate the association between torso muscle activity and torso twist. EMG data from five torso muscles and 3D motion capture data were recorded during 4x25m front crawl swimming trials at 400m and 50m pace (N=15). EMG data were integrated over 10ms intervals and normalized to the maximum value during each swimming trial (%iEMG) and torso twist acceleration was calculated as the second time derivative of the relative angle between thorax and pelvis about the longitudinal axis. Spearman correlations were calculated between 5th percentile scores of %iEMG and torso twist acceleration. Mean correlation coefficients were weak (i.e. r \u3c 0.30) for all muscles at both paces. The findings suggest that torso muscle activity may not be directly associated with torso twist acceleration

Development of forest structure and leaf area in secondary forests regenerating on abandoned pastures in Central Amazonia

The area of secondary forest (SF) regenerating from pastures is increasing in the Amazon basin; however, the return of forest and canopy structure following abandonment is not well understood. This study examined the development of leaf area index (LAI), canopy cover, aboveground biomass, stem density, diameter at breast height (DBH), and basal area ( BA) by growth form and diameter class for 10 SFs regenerating from abandoned pastures. Biomass accrual was tree dominated, constituting >= 94% of the total measured biomass in all forests abandoned >= 4 to 6 yr. Vine biomass increased with forest age, but its relative contribution to total biomass decreased with time. The forests were dominated by the tree Vismia spp. (> 50%). Tree stem density peaked after 6 to 8 yr ( 10 320 stems per hectare) before declining by 42% in the 12- to 14-yr-old SFs. Small-diameter tree stems in the 1-5-cm size class composed > 58% of the total stems for all forests. After 12 to 14 yr, there was no significant leaf area below 150-cm height. Leaf area return (LAI = 3.2 after 12 to 14 yr) relative to biomass was slower than literature-reported recovery following slash-and-burn, where LAI can reach primary forest levels ( LAI = 4 - 6) in 5 yr. After 12 to 14 yr, the colonizing vegetation returned some components of forest structure to values reported for primary forest. Basal area and LAI were 50% - 60%, canopy cover and stem density were nearly 100%, and the rapid tree-dominated biomass accrual was 25% - 50% of values reported for primary forest. Biomass accumulation may reach an asymptote earlier than expected because of even-aged, monospecific, untiered stand structure. The very slow leaf area accumulation relative to biomass and to reported values for recovery following slash-and-burn indicates a different canopy development pathway that warrants further investigation of causes ( e. g., nutrient limitations, competition) and effects on processes such as evapotranspiration and soil water uptake, which would influence long-term recovery rates and have regional implications

Community-based exercise and physical activity programmes led by exercise professionals for osteoarthritis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To assess the benefits and harms of community-based exercise and physical activity programmes led by non-healthcare exercise professionals for osteoarthritis, compared to those delivered by healthcare professionals, self-directed interventions, home-based programmes or continued general practitioner (GP) care

Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma

Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 x 10(6) human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). the experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. in the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. the recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001). the PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase in SERPINB5, a tumor suppressor gene, and a 10-fold higher expression of KISS I, a metastasis suppressor gene, in the treated group. Proangiogenic genes such as VEGFA, PDGFA and PDGFB were downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM.McGill Univ, Ctr Hlth, Dept Ophthalmol & Pathol, Montreal, PQ, CanadaHenry C Witelson Ocular Pathol Lab, Montreal, PQ, CanadaUniversidade Federal de São Paulo UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Increased susceptibility of Cantagalo virus to the antiviral effect of ST-246®

AbstractCantagalo virus (CTGV) is the etiologic agent of a pustular disease in dairy cows and dairy workers in Brazil with important economical and occupational impacts. Nevertheless, no antiviral therapy is currently available. ST-246 is a potent inhibitor of orthopoxvirus egress from cells and has proved its efficacy in cell culture and in animal models. In this work, we evaluated the effect of ST-246 on CTGV replication. Plaque reduction assays indicated that CTGV is 6–38 times more susceptible to the drug than VACV-WR and cowpox virus, respectively, with an EC50 of 0.0086μM and a selective index of >11,600. The analysis of β-gal activity expressed by recombinant viruses in the presence of ST-246 confirmed these results. In addition, ST-246 had a greater effect on the reduction of CTGV spread in comet tail assays and on the production of extracellular virus relative to VACV-WR. Infection of mice with CTGV by tail scarification generated primary lesions at the site of scarification that appeared less severe than those induced by VACV-WR. Animals infected with CTGV and treated with ST-246 at 100mg/kg for 5days did not develop primary lesions and virus yields were inhibited by nearly 98%. In contrast, primary lesions induced by VACV-WR were not affected by ST-246. The analysis of F13 (p37) protein from CTGV revealed a unique substitution in residue 217 (D217N) not found in other orthopoxviruses. Construction of recombinant VACV-WR containing the D217N polymorphism did not lead to an increase in the susceptibility to ST-246. Therefore, it is still unknown why CTGV is more susceptible to the antiviral effects of ST-246 compared to VACV-WR. Nonetheless, our data demonstrates that ST-246 is a potent inhibitor of CTGV replication that should be further evaluated as a promising anti-CTGV therapy

GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation

Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic β-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in β-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 β-cells and rodent islets to the GLP-1R agonist Exendin-4 (50nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18hours promotes metabolic reprogramming of β-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of HypoxiaInducible Factor 1 alpha (HIF-1α) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in β-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated β-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

Inovações na saúde pública: casos brasileiros premiados / Innovations in public health: awarded brazialian cases

A inovação em saúde utilizada neste artigo refere-se à aplicação de ideias, processos, produtos ou procedimentos que sejam relevantes para as unidades que as adotam que beneficiem o indivíduo, grupo ou sociedade em geral. O objetivo geral da pesquisa é analisar as configurações da inovação da Saúde Pública Brasileira. Essa pesquisa classifica-se como bibliográfica, documental, qualitativa e descritiva, sendo fontes de coleta de dados secundarias, baseadas no artigo Inovação em Serviços de Saúde no Brasil: análise dos casos premiados no Concurso de Inovação na Administração Pública Federal e no site Escola Nacional de Administração Pública (ENAP). Foram analisadas 19 experiências na área de saúde premiadas dos anos de 1995 a 2011, identificados no artigo, e no site (ENAP) 4 experiências premiadas nos de 2013 a 2016 especificadas nos resultados desta pesquisa.       Procurou-se dissertar sobre: Inovação, Tipos de Inovação e Inovação na Saúde Pública. Percebe-se com os estudos, incentivos governamentais à inovação no setor público demonstrando, assim que a administração pública se preocupa com as inovações realizadas na Saúde Pública

Pseudohipoaldosteronism Type 1: a case report supported by a literature review

In the neonatal period, hydro electrolytic disorders with dehydration and metabolic acidosis can cause admission to an intensive care unit and become a diagnostic challenge. Among such disorders, hyponatremia and hyperkalemia become diagnostic challenges with hormonal involvement, including aldosterone. Pseudohypoaldosteronism (PHA) resulting from the lack of response to aldosterone in target cells can be classified into three types and its suspected diagnosis in cases of hyponatremia, hyperkalemia with an elevation of serum aldosterone, can be confirmed by exome sequencing with identification of a potentially pathogenic. This study was based on the case report of a newborn of consanguineous parents who, after birth, evolved in the first week of life with shock, hyponatremia, hyperkalemia, and metabolic acidosis. An initial investigation ruled out congenital adrenal hyperplasia. The presence of hyperaldosteronism with increased plasma renin activity, associated with hyperkalemia and hyponatremia difficult to control with electrolyte replacement, led to a molecular investigation that confirmed PHA type 1 by a mutation in the SCCN1A gene. In neonates with severe hyponatremia that is difficult to resolve with conventional treatment and elevation of serum aldosterone, this pathology must be remembered and investigated, avoiding high morbidity and mortality