The population impact of rheumatic and musculoskeletal diseases in relation to other non-communicable disorders: comparing two estimation approaches

The aim of this study was to quantify the population impact of rheumatic and musculoskeletal diseases (RMDs) with other non-communicable diseases (NCDs), using two complementary strategies: standard multivariate models based on global burden of disease (GBD)-defined groups vs. empirical mutually exclusive patterns of NCDs. We used cross-sectional data from the Portuguese Fourth National Health Survey (n = 23,752). Six GBD-defined groups were included: RMDs, chronic obstructive pulmonary disease or asthma, cancer, depression, diabetes or renal failure, and stroke or myocardial infarction. The empirical approach comprised the patterns “low disease probability”, “cardiometabolic conditions”, “respiratory conditions” and “RMDs and depression”. As recommended by the outcome measures in rheumatology (OMERACT) initiative, health outcomes included life impact, pathophysiological manifestations, and resource use indicators. Population attributable fractions (PAF) were computed for each outcome and bootstrap confidence intervals (95% CI) were estimated. Among GBD-defined groups, RMDs had the highest impact across all the adverse health outcomes, from frequent healthcare utilization (PAF 7.8%, 95% CI 6.2–9.3) to negative self-rated health (PAF 18.1%, 95% CI 15.4–20.6). In the empirical approach, patterns “cardiometabolic conditions” and “RMDs and depression” had similar PAF estimates across all adverse health outcomes, but “RMDs and depression” showed significantly higher impact on chronic pain (PAF 8.9%, 95% CI 7.6–10.3) than the remaining multimorbidity patterns. RMDs revealed the greatest population impact across all adverse health outcomes tested, using both approaches. Empirical patterns are particularly interesting to evaluate the impact of RMDs in the context of their co-occurrence with other NCDs.This study received no specific funding. The funding for EPI Unit is obtained from the National Foundation for Science and Technology (FCT UID/DTP/04750/2013/002). FAA is supported by Grant FCT SFRH/BD/85398/2012, TM by Grant FCT SFRH/BD/92370/2013 and RL by Grant FCT SFRH/BPD/88729/2012

Occupational participation, stress, anxiety and depression in workers and students from Brazilian universities during the COVID-19 pandemic

Abstract Introduction The physical, social and occupational restrictions imposed by the COVID-19 pandemic have affected the health and well-being of the world population. Objective To identify the repercussions of the pandemic on the occupational participation of students, lecturers and technicians from three public universities in Northern Brazil, to compare the changes reported by participants in occupational participation before and during the pandemic, and to identify symptoms of depression, anxiety and stress self-reported. Method This is a Cross-sectional, descriptive and comparative study with a quantitative approach. One hundred and ninety-nine (n = 199) participants (students, lecturers and technicians) responded to an online questionnaire, the “Occupational Participation Checklist” and the Anxiety, Stress and Depression Scale (DASS-21). Data analysis were descriptive and also performed by applying the Wilcoxon and Mann-Whitney tests. Results During the pandemic, an increase in occupational participation was identified for all participants in domestic activities (p <0.001) and a decrease in work and study face to face (p <0.001). Students reported more symptoms of depression, anxiety and stress when compared to lecturers (p<0.001). Most students did not organise their time to fulfil their occupations with satisfaction. Such difficulties were associated with symptoms of depression, anxiety and stress, especially among the student's group (p<0.001). Conclusion This study provided preliminary evidence about differences in occupational participation before and during the Covid-19 pandemic. The organization of time and difficulties in occupational participation were associated to levels of anxiety, depression and stress, especially in the sample of students

Interplaying Cassandra NoSQL Consistency and Performance: A Benchmarking Approach

This experience report analyses performance of the Cassandra NoSQL database and studies the fundamental trade-off between data consistency and delays in distributed data storages. The primary focus is on investigating the interplay between the Cassandra performance (response time) and its consistency settings. The paper reports the results of the read and write performance benchmarking for a replicated Cassandra cluster, deployed in the Amazon EC2 Cloud. We present quantitative results showing how different consistency settings affect the Cassandra performance under different workloads. One of our main findings is that it is possible to minimize Cassandra delays and still guarantee the strong data consistency by optimal coordination of consistency settings for both read and write requests. Our experiments show that (i) strong consistency costs up to 25% of performance and (ii) the best setting for strong consistency depends on the ratio of read and write operations. Finally, we generalize our experience by proposing a benchmarking-based methodology for run-time optimization of consistency settings to achieve the maximum Cassandra performance and still guarantee the strong data consistency under mixed workloads

Hyperglycaemia and diabetes impair gap junctional communication among astrocytes

Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15–25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin)-treated rats at 20–24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin) 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs

Integer and half-integer flux-quantum transitions in a niobium/iron-pnictide loop

The recent discovery of iron-based superconductors challenges the existing paradigm of high-temperature superconductivity. Owing to their unusual multi-orbital band structure, magnetism, and electron correlation, theories propose a unique sign reversed s-wave pairing state, with the order parameter changing sign between the electron and hole Fermi pockets. However, because of the complex Fermi surface topology and material related issues, the predicted sign reversal remains unconfirmed. Here we report a novel phase-sensitive technique for probing unconventional pairing symmetry in the polycrystalline iron-pnictides. Through the observation of both integer and half-integer flux-quantum transitions in composite niobium/iron-pnictide loops, we provide the first phase-sensitive evidence of the sign change of the order parameter in NdFeAsO0.88F0.12, lending strong support for microscopic models predicting unconventional s-wave pairing symmetry. These findings have important implications on the mechanism of pnictide superconductivity, and lay the groundwork for future studies of new physics arising from the exotic order in the FeAs-based superconductors.Comment: 23 pages, including 4 figures and supplementary informatio

Superconformal Flavor Simplified

A simple explanation of the flavor hierarchies can arise if matter fields interact with a conformal sector and different generations have different anomalous dimensions under the CFT. However, in the original study by Nelson and Strassler many supersymmetric models of this type were considered to be 'incalculable' because the R-charges were not sufficiently constrained by the superpotential. We point out that nearly all such models are calculable with the use of a-maximization. Utilizing this, we construct the simplest vector-like flavor models and discuss their viability. A significant constraint on these models comes from requiring that the visible gauge couplings remain perturbative throughout the conformal window needed to generate the hierarchies. However, we find that there is a small class of simple flavor models that can evade this bound.Comment: 43 pages, 1 figure; V3: small corrections and clarifications, references adde

An introduction to Graph Data Management

A graph database is a database where the data structures for the schema and/or instances are modeled as a (labeled)(directed) graph or generalizations of it, and where querying is expressed by graph-oriented operations and type constructors. In this article we present the basic notions of graph databases, give an historical overview of its main development, and study the main current systems that implement them

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation.

Mast cell activation through the high-affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI-mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE-mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE-mediated mast cell activation. To this end, bone marrow-derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross-linking. The results indicated that VPA reduced mast cell IgE-dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE-mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE-mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse