Lack of Fibronectin Extra Domain A Alternative Splicing Exacerbates Endothelial Dysfunction in Diabetes

Glucose-induced changes of artery anatomy and function account for diabetic vascular complications, which heavily impact disease morbidity and mortality. Since fibronectin containing extra domain A (EDA\u2009+\u2009FN) is increased in diabetic vessels and participates to vascular remodeling, we wanted to elucidate whether and how EDA\u2009+\u2009FN is implicated in diabetes-induced endothelial dysfunction using isometric-tension recording in a murine model of diabetes. In thoracic aortas of EDA(-/-), EDA(+/+) (constitutively lacking and expressing EDA\u2009+\u2009FN respectively), and of wild-type mice (EDA(wt/wt)), streptozotocin (STZ)-induced diabetes impaired endothelial vasodilation to acetylcholine, irrespective of genotype. However STZ\u2009+\u2009EDA(-/-) mice exhibited increased endothelial dysfunction compared with STZ\u2009+\u2009EDA(+/+) and with STZ\u2009+\u2009EDA(wt/wt). Analysis of the underlying mechanisms revealed that STZ\u2009+\u2009EDA(-/-) mice show increased oxidative stress as demonstrated by enhanced aortic superoxide anion, nitrotyrosine levels and expression of NADPH oxidase NOX4 and TGF-\u3b21, the last two being reverted by treatment with the antioxidant n-acetylcysteine. In contrast, NOX1 expression and antioxidant potential were similar in aortas from the three genotypes. Interestingly, reduced eNOS expression in STZ\u2009+\u2009EDA(+/+) vessels is counteracted by increased eNOS coupling and function. Although EDA\u2009+\u2009FN participates to vascular remodelling, these findings show that it plays a crucial role in limiting diabetic endothelial dysfunction by preventing vascular oxidative stress

Organiza??o geral de uma empresa rural localizada em Caxambu do Sul - SC

Diante do contexto econ?mico atual, aonde v?rias empresas v?m encerrando suas atividades, aquelas que possuem uma gest?o eficaz, eficiente e est?o organizadas possuem uma chance maior de se manterem ativas no mercado. O presente trabalho de conclus?o de curso possui como justificativa o fato de n?o se ver muitos estudos acad?micos relacionados ? gest?o das empresas rurais, estas que como as outras empresas tamb?m s?o importantes para a economia do Pa?s. Na regi?o Sul a agricultura familiar ? predominante, necessitando assim de estudos mais aprofundados, pois estas s?o administradas por empres?rios que det?m pouco conhecimento de gest?o empresarial. No presente estudo tem-se por objetivo propor a organiza??o geral de uma empresa rural. Para tanto foi realizado um diagn?stico organizacional, onde analisou-se quais processos e controles os empres?rios rurais aplicam em sua propriedade atualmente e a partir de ent?o foram sugeridas novos processos e controles, al?m de sugeridos planos e programas que fossem vi?veis para a mesma. Tamb?m utilizou-se de base te?rica para explicar e fundamentar como funcionam as empresas rurais e a agricultura familiar, onde realizadou-se entrevista e observa??o direta para a coleta dos dados. Por fim, apresentam-se as considera??es em rela??o ? aplicabilidade do trabalho, assim como as ferramentas criadas para auxiliar os empres?rios em suas atividades

Gest?o escolar democr?tica e a participa??o da fam?lia na educa??o infantil

Gest?o escolar democr?tica e a participa??o da fam?lia na Educa??o Infantil, tem os objetivos de compreender como o atendimento da educa??o infantil foi acontecendo no Brasil, promover uma reflex?o a cerca dos fatores que dificultam ou impedem uma participa??o efetiva dos pais na vida escolar dos filhos e as contribui??es do gestor neste contexto educativo. Como m?todo de pesquisa foi utilizado uma pesquisa de campo com a aplica??o de question?rios em tr?s Centros Municipais de Educa??o Infantil do munic?pio de Concordia ? SC, localizados em diferentes regi?es, dois na ?rea urbana, comtemplando centro bairro, e meio rural. Sendo a fam?lia o primeiro contexto de educa??o da crian?a, na Educa??o Infantil a parceria deve ser o ponto inicial do trabalho. No entanto para que isso aconte?a o gestor deve compartilhar este espa?o com as fam?lias, em um trabalho coletivo, que demonstre um olhar atento para o contexto em que est?o inseridas construindo rela??es mais democr?ticas. Para isso deve-se aproveitar o m?ximo todas as possibilidades de estreitamento de rela??es abrindo espa?o de conviv?ncia, socializa??o e parceria para o desenvolvimento de uma educa??o de qualidade e uma gest?o democr?tica

The alpha-7 nicotinic acetylcholine receptor is involved in a direct inhibitory effect of nicotine on GnRH release : In vitro studies

The activation of nicotinic cholinergic receptors (nAChR) inhibits the reproductive axis; however, it is not clear whether nicotine may directly modulate the release of hypothalamic gonadotropin-releasing hormone (GnRH). Experiments carried out in GT1-1 immortalized GnRH neurons reveal the presence of a single class of high affinity \u3b14\u3b22 and \u3b17 nAchR subtypes. The exposure of GT1-1\ua0cells to nicotine does not modify the basal accumulation of GnRH. However, nicotine was found to modify GnRH pulsatility in perifusion experiments and inhibits, the release of GnRH induced by prostaglandin E1 or by K(+)-induced cell depolarization; these effects were reversed by D-tubocurarine and \u3b1-bungarotoxin. In conclusion, the results reported here indicate that: functional nAChRs are present on GT1-1\ua0cells, the activation of the \u3b1-bungarotoxin-sensitive subclass (\u3b17) produces an inhibitory effect on the release of GnRH and that the direct action of nicotine on GnRH neurons may be involved in reducing fertility of smokers

Stranded asset implications of the Paris Agreement in Latin America and the Caribbean

Achieving the Paris Agreement's near-term goals (nationally determined contributions, or NDCs) and long-term temperature targets could result in pre-mature retirement, or stranding, of carbon-intensive assets before the end of their useful lifetime. We use an integrated assessment model to quantify the implications of the Paris Agreement for stranded assets in Latin America and the Caribbean (LAC), a developing region with the least carbon-intensive power sector in the world. We find that meeting the Paris goals results in stranding of $37-90 billion and investment of$1.9-2.6 trillion worth of power sector capital (2021-2050) across a range of future scenarios. Strengthening the NDCs could reduce stranding costs by 27%-40%. Additionally, while politically shielding power plants from pre-mature retirement or increasing the role of other sectors (e.g. land-use) could also reduce power sector stranding, such actions could make mitigation more expensive and negatively impact society. For example, we find that avoiding stranded assets in the power sector increases food prices 13%, suggesting implications for food security in LAC. Our analysis demonstrates that climate goals are relevant for investment decisions even in developing countries with low emissions. © 2020 The Author(s). Published by IOP Publishing Ltd

Cost-Effectiveness Analysis of Apixaban Versus Edoxaban in Patients with Atrial Fibrillation for Stroke Prevention

OBJECTIVE: Our objective was to assess the cost effectiveness of apixaban versus edoxaban in the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) in Spain. METHODS: We customized a Markov model with ten health states to estimate the lifetime economic and clinical outcomes in 6-week cycles. The efficacy (clinical event rates per 100 patient-years) and safety data were derived from a pairwise indirect treatment comparison. The analysis was conducted from both the national health service (NHS) and societal perspectives, and included pharmaceutical costs (retail price plus value-added tax (VAT) and applicable national deductions) according to daily dosages (apixaban 10 mg (5 mg twice daily (bid)) and edoxaban 60 or 30 mg) and complications and disease-management costs, obtained from national databases. Utilities for quality-adjusted life-year (QALY) calculations reflected EuroQoL 5-Dimension scores in patients with AF. An annual discount rate of 3% was applied for costs (euro, year 2019 values) and outcomes. RESULTS: In a 1000-patient cohort, apixaban 5 mg bid versus edoxaban 60 mg could avoid five strokes, six major bleedings and 29 clinically relevant non-major bleedings (CRNMBs). Compared with edoxaban 30 mg, apixaban could avoid 21 strokes and two SEs. An increase in bleedings was observed with apixaban (seven haemorrhagic strokes, 48 major bleedings and 17 CRNMBs). Apixaban yielded 0.04 additional QALYs compared with edoxaban 60 mg or 30 mg. Incremental costs/QALY were euro9639.33 and euro354.22 for apixaban versus edoxaban 60 mg and edoxaban 30 mg, respectively, from the NHS perspective and euro7756.62 for apixaban versus edoxaban 60 mg from the societal perspective. Apixaban was dominant versus edoxaban 30 mg from the societal perspective. Sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This study suggests that apixaban 5 mg bid is a cost-effective alternative to edoxaban for stroke prevention in the AF population in Spain