Are objective measures of sleep and sedentary behaviours related to low back pain flares?

Final peer-reviewed manuscript[Abstract] Risk factors for low back pain (LBP) flares have been considered about self-reported measures. This case–crossover study aimed to investigate whether (1) objective measures of physical activity and sleep were associated with the risk of experiencing LBP flares and (2) these associations differed for flares defined as pain 2 or more points greater than average pain over the period using an 11-point Numerical rating scale (0-no pain and 10-worst pain imaginable) (pain-defined flare: PDF) and flares identified by participants according to a broader definition that considered emotions or coping (self-reported flare [SRF]). We included 126 participants who had experienced LBP for >3 months. Physical activity and sleep were monitored for 28 days using wearable sensors. Occurrence of flares (PDF or SRF) was assessed daily using a smartphone application. Data on exposure to risk factors 1, 2, and 3 days preceding PDF or SRF were compared with nonflare control periods. Conditional logistic regression determined association between each factor and flares. Data show that day-to-day variation in physical activity and in-bed time are associated with the risk of LBP flares, but associations differ depending on how flare is defined. Longer in-bed time increased the risk of PDF but not SRF. Although physical activity was not associated with the risk of PDF, greater sedentary behaviour increased the risk of SRF and being more physically active decreased the risk for SRF. These results highlight the potential role of targeting sleep and physical activity in interventions to prevent LBP flares and indicate that risk factors differ depending on how LBP flares are defined.Centre of Research Excellence (Australia); APP1091302Centre of Research Excellence (Australia); APP1079078National Health and Medical Research Council (NHMRC) of Australia; PH—APP1102905National Health and Medical Research Council (NHMRC) of Australia; MF—APP114359

How is symptom flare defined in musculoskeletal conditions: a systematic review

To systematically review the definitions for "flare" in musculoskeletal conditions, the derivation processes, and validation of definitions for the 12 most burdensome musculoskeletal conditions.A literature search was conducted in MEDLINE, EMBASE, CINAHL, AMED, PsycInfo and Lilacs to identify studies that investigated derivation or validation of a flare definition, which we considered as a phrase or group of domains.Reports of derivation of flare definitions were identified for 9/12 musculoskeletal conditions. Validation of flare definitions was initiated for 4/12. For each condition, different derivation and validation methods have been used, with variable levels of consumer involvement, and in some cases different groups have worked on the process in parallel. Although some flare definitions began simply as "symptom worsening" or "change in treatment", most evolved into multidimensional definitions that include: pain, impact on function, joint symptoms, and emotional elements. Frequently initial attempts to create phrase to define the term flare evolved into consensus on the breadth of domains involved. Validation has compared flare definitions/domains against measures of disease activity, clinicians' diagnosis, response to drug therapy, or a combination.This review suggests that greater characterisation and definition of flares in musculoskeletal conditions are linked to the inclusion of multiple perspectives, multifaceted domains and compound comparators for their validation. Further work is required to optimise and test the derived definitions for most musculoskeletal conditions. As some elements are disease-specific, flare definitions cannot be extrapolated to other conditions. Research regarding flare in back pain (most burdensome disease) is limited

Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregationres

Altres ajuts: SUDOE INTERREG IV B (SOE4/P1/E831 to S.V.) and FEDER funds through the Operational Competitiveness Programme - COMPETE [grant number FCOMP-01-0124-FEDER-022718 (PEST-c/SAU/LA0002/2011) FCT-FEDER forunit 4293 in partnership with PT2020].More than a hundred different Transthyretin (TTR) mutations are associated with fatal systemic amyloidoses. They destabilize the protein tetrameric structure and promote the extracellular deposition of TTR as pathological amyloid fibrils. So far, only mutations R104H and T119M have been shown to stabilize significantly TTR, acting as disease suppressors. We describe a novel A108V non-pathogenic mutation found in a Portuguese subject. This variant is more stable than wild type TTR both in vitro and in human plasma, a feature that prevents its aggregation. The crystal structure of A108V reveals that this stabilization comes from novel intra and inter subunit contacts involving the thyroxine (T 4) binding site. Exploiting this observation, we engineered a A108I mutation that fills the T 4 binding cavity, as evidenced in the crystal structure. This synthetic protein becomes one of the most stable TTR variants described so far, with potential application in gene and protein replacement therapies

Efferent Pathways in Sodium Overload-Induced Renal Vasodilation in Rats

Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. the present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. in anesthetized rats (n = 6), OT infusion (0.03 mu g . kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml . kg(-1) b.wt., i.v.) was infused over 60 s. in sham rats (n = 6), hypertonic saline induced renal vasodilation. the OXTR antagonist (AT; atosiban, 40 mu g . kg(-1) . h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. the combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Goias, Ctr Neurosci & Cardiovasc Physiol, Inst Biol Sci, Dept Physiol Sci, Goiania, Go, BrazilUniv Fed Uberlandia, Fac Phys Educ, Inst Biol Sci, BR-38400 Uberlandia, MG, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniv Fed Goias, Inst Biol Sci, Mol Biol Lab, Goiania, Go, BrazilUniv Fed Goias, Inst Biol Sci, Dept Biochem & Mol Biol, Goiania, Go, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilFundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2012/0055431086Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2009/10267000352CNPq: 477832/2010-5CNPq: 483411/2012-4Web of Scienc

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

A definition of flare in low back pain (LBP): A multiphase process involving perspectives of individuals with LBP and expert consensus

Low back pain (LBP) varies over time. Consumers, clinicians and researchers use various terms to describe fluctuations of LBP symptoms. Although "flare" is commonly used to describe symptom fluctuation, there is no consensus on how it is defined. This study aimed to obtain consensus for a LBP flare definition using a mixed-method approach. Step 1 involved derivation of a preliminary candidate flare definition based on thematic analysis of consumers' views in consultation with an expert consumer writer. In Step 2, a workshop was conducted to incorporate perspectives of LBP experts into the preliminary flare definition, which resulted in two alternative LBP flare definitions. Step 3 refined the definition using a two-round Delphi consensus process with experts in musculoskeletal conditions. The definition favoured by experts was further tested with individuals with LBP in Step 4, using the definition in three scenarios. This multiphase study produced a LBP flare definition that distinguishes it from other LBP fluctuations, represents views of consumers, involves expert consensus, and is understandable by consumers in clinical and research contexts: "A flare-up is a worsening of your condition that lasts from hours to weeks that is difficult to tolerate and generally impacts your usual activities and/or emotions". Perspective: A multiphase processes produced a low back pain (LBP) flare definition that distinguishes it from other LBP fluctuations, involves expert consensus and represents consumers' views

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio