Trends in concussions at Ontario schools prior to and subsequent to the introduction of a concussion policy - an analysis of the Canadian hospitals injury reporting and prevention program from 2009 to 2016

Background: Concussion is a preventable injury that can have long-term health consequences for children and youth. In Ontario, the Policy/Program Memorandum # 158 (PPM) was introduced by the Ministry of Education of Ontario in March 2014. The PPM’s main purpose is to require each school board in the province to create and implement a concussion policy. The purpose of this paper is to examine trends in school-based concussions prior to and subsequent to the introduction of the PPM. Methods: This report examined emergency department (ED) visits in 5 Ontario hospitals that are part of the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), and compared trends over time in diagnosed concussions, and suspected concussions identified as “other head injury” in children and youth aged 4–18. Results: From 2009 to 2016 study years, there were 21,094 suspected concussions, including 8934 diagnosed concussions in youth aged 4–18. The average number of diagnosed concussions in the 5 years before the PPM was 89 concussions/month, compared to approximately 117 concussions per month after; a 30% increase in the monthly rate of concussions presenting to the ED. The total number of concussion or head injury-related ED visits remained relatively unchanged but the proportion of diagnosed concussions rose from 31% in 2009 to 53% in 2016. The proportion of diagnosed concussions in females also increased from 38% in 2013 to 46% in 2016. The percent of all diagnosed concussions occurring at schools increased throughout the study reaching almost 50% in 2016 with most injuries taking place at the playground (24%), gymnasium (22%) or sports field (20%). Conclusions: The introduction of the PPM may have contributed to a general increase in concussion awareness and an improvement in concussion identification at the school level in children and youth aged 4–18. Keywords: Concussion, Policy, Emergency department, YouthYork University Librarie

Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes.

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways occurs through regulation of activity and availability of mothers against DPP (Drosophila) human homologue (Smad) proteins. METHODS: Human articular chondrocytes isolated from knee joints from patients with osteoarthritis (OA) or normal bovine chondrocytes were cultured in suspension in poly-(2-hydroxyethyl methacrylate)-coated dishes with either 10% fetal bovine serum media or serum-deprived media 6h before treatment with IL-1beta alone, TNF-alpha alone or IL-1beta followed by TGF-beta. Nuclear extracts were examined by electrophoretic mobility-shift assays (EMSA) for nuclear factor-kappa B (NF-kappaB) and Smad3/4 deoxyribonucleic acid (DNA) binding. Nuclear extracts were also subjected to the TranSignal Protein/DNA array (Panomics, Redwood City, CA) enabling the simultaneous semiquantitative assessment of DNA-binding activity of 54 different transcription factors. Nuclear phospho-Smad2/3 and total Smad7 protein expression in whole cell lysates were studied by Western blot. Cytoplasmic Smad7, type II collagen alpha 1 (COL2A1), aggrecan and SRY-related high mobility group-Box gene 9 (SOX-9) mRNA expression were measured by real-time polymerase chain reaction (PCR). RESULTS: The DNA-binding activity of Smad3/4 in the TranSignal Protein/DNA array was downregulated by TNF-alpha (46%) or IL-1beta treatment (42%). EMSA analysis showed a consistent reduction in Smad3/4 DNA-binding activity in human articular chondrocytes treated with IL-1beta or TNF-alpha. TGF-beta-induced Smad3/4 DNA-binding activity and Smad2/3 phosphorylation were also reduced following pretreatment with IL-1beta in human OA and bovine chondrocytes. Real-time PCR and Western blot analysis showed that IL-1beta partially reversed the TGF-beta stimulation of Smad7 mRNA and protein levels in TGF-beta-treated human OA cells. In contrast, TGF-beta-stimulated COL2A1, aggrecan, and SOX-9 mRNA levels were abrogated by IL-1beta. CONCLUSIONS: IL-1beta or TNF-alpha exerted a suppressive effect on Smad3/4 DNA-binding activity in human articular chondrocytes, as well as on TGF-beta-induced stimulation of Smad3/4 DNA-binding activity and Smad2/3 phosphorylation in human OA and bovine articular chondrocytes. IL-1beta partially reversed the increase in TGF-beta-stimulated Smad7 mRNA or protein levels suggesting that Smad7 may not be involved in the suppression of TGF-beta signaling induced by IL-1beta or TNF-alpha in articular chondrocytes. The balance between the IL-1beta or TNF-alpha and the TGF-beta signaling pathways is crucial for maintenance of articular cartilage homeostasis and its disruption likely plays a substantial role in the pathogenesis of OA

Therapeutic applications of SAMMSON lncRNA inhibition in uveal melanoma

Uveal melanoma is the most common intraocular malignancy in adults. The lack of an effective treatment results in a median survival time less than one year for patients with metastatic disease. Recently, our lab identified the melanoma-specific long non-coding RNA (lncRNA) SAMMSON as a novel therapeutic target in skin melanoma. Analysis of a PAN cancer RNA-sequencing dataset revealed consistent expression of SAMMSON in uveal melanoma tumors. Although SAMMSON expression was lower in uveal compared to skin melanoma, over 90% of uveal melanoma tumors showed detectable SAMMSON expression. Further analysis also revealed SAMMSON expression in conjunctival melanoma, another form of ocular melanoma. To evaluate the therapeutic potential of SAMMSON inhibition in uveal and conjunctival melanoma, we treated 8 representative cell lines with SAMMSON-specific ASOs and observed a strong reduction in cell viability, accompanied by induction of apoptosis. In line with the role of SAMMSON in modulating mitochondrial metabolism, SAMMSON knock down resulted in decreased mitochondrial oxygen consumption. Uveal melanomas are characterized by activated MEK-signaling through mutations in GNA11/GNAQ. Combining SAMMSON-specific ASOs with the MEK-inhibitor Trametinib, induced strong synergistic effects, resulting in a nearly complete abrogation of tumor cells at nanomolar concentrations of Trametinib. The in vivo effects of SAMMSON inhibition, whether or not in combination with Trametinib, are currently being investigated in a uveal melanoma PDX model. Together, our results demonstrate the efficacy of SAMMSON inhibition as a novel treatment option for uveal melanoma and demonstrate its synergism with MEK inhibition making SAMMSON a promising anti-cancer target for uveal melanoma patients

Targeting NF-kappaB: a promising molecular therapy in inflammatory arthritis.

The nuclear factor-kappa B family of transcription factors is intimately involved in the regulation of the inflammatory responses that play a fundamental role in the damage of articular tissues. Thus, many studies have examined the important contributions of components of the NF-kappaB signaling pathways to the pathogenesis of various rheumatic diseases and their pharmacologic modulation. Currently available therapeutic agents including nonsteroidal anti-inflammatory drugs, corticosteroids, nutraceuticals, and disease-modifying antirheumatic drugs, as well as novel specific small-molecule inhibitors have been employed. In addition, promising nucleic acid-based strategies have shown encouraging results. However, further research will be needed before NF-kappaB-aimed strategies become an effective therapy for inflammatory arthritis

Melhoria da Atenção à Saúde dos Usuários HAS e/ou DM da UBS Sete de Setembro, Santa Rosa/RS

Este trabalho tem por objetivo melhorar o atendimento de usuários com HAS e / ou DM na UBS( unidade básica de saúde) Sete de Setembro em Santa Rosa/RS. Acredito que depois de desenvolver nosso projeto de intervenção a população sera mais consciente de seu ato-cuidado e tecas uma ideia avacada de que este tipo de doenças são responsareis de importantes costos econômicos, pessoaias,familiares, e sociais. Em cada uns dos capítulos intentamos fazer uma mostra nossa realidade assim como as estrategias para conseguir atingir as necessidades de nossa população. Este volume é um fiel reflexo de nossa realidade que é comentada na análise situacional descrita no CAPITULO 1, onde se expõem os motivos que foram as principais forças que determinaram o desenvolvimento deste trabalho. No CAPITULO 2 está descrito os objetivos, metas, indicadores e estratégias empregadas para tal fim. No CAPITULO 3 apresenta-se o relatório da intervenção, no CAPITULO 4 descreve-se os resultados e discussão da mesma. Os CAPITULOS 5 e 6 estão descritos os relatórios para gestores e comunidade e por fim apresenta-se uma reflexão crítica sobre o processo pessoal de aprendizagem, após estão descritas as referências apêndices e anexo

Repeatability: some aspects concerning the evaluation of the measurement uncertainty

Various publications stress the importance of the repeatability (i.e. precision) of the calculation of the measurement of uncertainty. We reveal by detailing an example from production control in the pharmaceutical industry that the effect of other influence quantities should not be neglected, because their magnitude is even larger than the contribution of repeatability. We review the role of repeatability within the calculation of measurement uncertainty for several common validation and day-to-day measurement scenarios. They show that measurement models need to consider the measurement sequences of the various scenarios. Otherwise the size and effect of the repeatability might be overestimated. At the end Monte Carlo simulations were used to investigate the determination of the repeatability under certain restrictions. The simulation uncovered a significant bias toward the common formula for calculating the standard deviation when it is based on a duplicated measurement of a sampl

Simplicial Models for the Epistemic Logic of Faulty Agents

In recent years, several authors have been investigating simplicial models, a model of epistemic logic based on higher-dimensional structures called simplicial complexes. In the original formulation, simplicial models were always assumed to be pure, meaning that all worlds have the same dimension. This is equivalent to the standard S5n semantics of epistemic logic, based on Kripke models. By removing the assumption that models must be pure, we can go beyond the usual Kripke semantics and study epistemic logics where the number of agents participating in a world can vary. This approach has been developed in a number of papers, with applications in fault-tolerant distributed computing where processes may crash during the execution of a system. A difficulty that arises is that subtle design choices in the definition of impure simplicial models can result in different axioms of the resulting logic. In this paper, we classify those design choices systematically, and axiomatize the corresponding logics. We illustrate them via distributed computing examples of synchronous systems where processes may crash