Von Willebrand Factor multimerization and the polarity of secretory pathways in endothelial cells

The Von Willebrand factor (VWF) synthesised and secreted by endothelial cells is central to haemostasis and thrombosis, providing a multifunctional adhesive platform that brings together components needed for these processes. VWF secretion can occur from both apical and basolateral sides of endothelial cells, and from constitutive, basal and regulated secretory pathways, the latter two via Weibel-Palade bodies (WPB). Although the amount and structure of VWF is crucial to its function, the extent of VWF release, multimerization and polarity of the three secretory pathways have only been addressed separately and with conflicting results. We set out to clarify these relationships using polarized Human Umbilical Vein Endothelial Cells (HUVECs) grown on Transwell membranes. We found that regulated secretion of Ultra large (UL) molecular weight VWF predominantly occurred apically, consistent with a role in localised platelet capture in the vessel lumen. We found that constitutive secretion of low molecular weight (LMW) VWF is targeted basolaterally, toward the subendothelial matrix, using the adaptor protein complex 1 (AP-1), where it may provide the bulk of collagen bound subendothelial VWF. We also found that basally-secreted VWF is composed of UL-VWF, released continuously from WPBs in the absence of stimuli, and occurs predominantly apically, suggesting this could be the main source of circulating plasma VWF. Together, we provide a unified dataset reporting the amount and multimeric state of VWF secreted from the constitutive, basal and regulated pathways in polarized HUVECs, and have established a new role for AP-1 in the basolateral constitutive secretion of VWF

Animal welfare concepts and strategy for poultry production: a review

Well being of animals had been historically a public concern, since the beginning of human kind history. As world's population grows there is a need for food including meat. In the last decades there has been a great improvement in poultry production based on the careful control of several aspects, among which nutrition and management (environment, health and rearing systems). Nowadays, the search for good welfare conditions is a global tendency in animal production; however issues surrounding farm animal welfare or well-being, such as definitions, measurements, interpretation, and perception, continue to be controversial. It is known that the result of a broiler not adequately housed is a direct loss in production which leads towards a thought that health, welfare and productivity are intimately connected. In the other hand hints are found in the observation of behavioral responses as well as vocalization, which may provide more precise assessment to welfare. This has been possible due to the use of information technology applied to the field of ethology as well as the multidisciplinary view of the problem. This text provides a review on broiler's welfare issues since its definition to several way of trying to assess it adequately.13714

Lessons from monochorionic twin delivery

The presence of acute peripartum anaemia in a monochorionic twin pregnancy represents a clinical challenge requiring prompt recognition and management. Twin-to-twin transfusion syndrome (TTTS) is a major complication of these pregnancies and a medical emergency in its acute form. Acute intrapartum fetoplacental transfusion (AIFT) has been reported infrequently. The authors present a case of a probable acute TTTS in an uneventful monochorionic monoamnionic twin pregnancy, where typical ultrasound criteria for long-standing TTTS were absent. The first twin was born pale, hypotonic and developed hypovolemic shock due to acute anaemia. Soon after birth, she presented with seizures and a cerebral ultrasound detected a large parieto-occipital infarction. The second twin, although plethoric, was clinically well. The risk of acute TTTS and AIFT, although infrequent and unpredictable, should be kept in mind when planning delivery of monochorionic twins, because the consequences for one or both twins can be disastrous

Successful management of bilateral orbital metastases from invasive lobular breast cancer with abemaciclib and letrozole: a case report and literature review

Breast cancer is a significant global health concern, contributing to substantial morbidity and mortality among women. Hormone receptor-positive (HR+)/HER2- negative (HER2-) breast cancer constitutes a considerable proportion of cases, and significant advancements have been made in its management. CDK4/6 inhibitors (CDK4/6is) are a new targeted therapy that has demonstrated efficacy in adjuvant, advanced and metastatic settings. The propensity of lobular breast carcinomas for estrogen-rich sites, such as periocular tissues and orbital fat, may explain their tendency for orbital metastases. Current treatment strategies for these cases are predominantly palliative, and the prognosis remains poor. This article presents a unique case of a 51-year-old female with progressive right periorbital edema, pain, and limited ocular motility. An imaging work-up showed bilateral intra and extraconal orbital infiltration, which was biopsied. The histopathologic analysis disclosed mild chronic inflammatory infiltrate with thickened fibrous tissue and moderately differentiated lobular carcinoma cells, positive for GATA3 and CK7 markers, with 100% of tumor nuclei expressing estrogen receptors (ER+). A systemic evaluation showed a multicentric nodular formation in both breasts. Further diagnostic assessments unveiled an HR+/HER2- bilateral lobular breast carcinoma with synchronous bilateral orbital metastases. Systemic treatment was initiated with abemaciclib 150mg twice daily and letrozole 2.5mg once a day. However, this regimen was interrupted due to toxicity. After two weeks, treatment was resumed with a reduced abemaciclib dose (100mg twice daily) alongside letrozole, with a reasonable tolerance. Nearly two years after the initial diagnosis of inoperable metastatic cancer, the patient remains on the same systemic treatment regimen with no signs of invasive disease. This case report is the first of a patientpresenting with bilateral orbital metastases from bilateral lobular breast cancer, showing an impressive and sustained response to a first-line treatment regimen combining abemaciclib and letrozole. A literature review on bilateral orbital metastases from breast cancer is also presented.info:eu-repo/semantics/publishedVersio

Valorização do trabalho humano: uma diretriz constitucional esquecida em meio à crise econômica e às consequentes propostas flexibilizantes

RESUMO: A flexibilização dos direitos trabalhistas é assunto em evidência na realidade econômica de nosso país, mormente em meio ao cenário de crise econômica que vivenciamos. O objetivo deste trabalho é refletir sobre a compatibilidade entre o raciocínio econômico, que entoa as atuais propostas de relativização da legislação trabalhista, e as balizas jurídicas conformadoras da Ordem Econômica constitucional, em especial o valor social do trabalho humano.  Por meio de pesquisa bibliográfica e análise normativa constitucional e infraconstitucional, será realizada, primeiramente, uma digressão sobre a evolução do ordenamento jurídico protetivo trabalhista e das propostas flexibilizantes que o acompanham na história.  Uma vez observado o histórico atrito entre os interesses empresariais e a proteção social trabalhista, o trabalho se ocupará em aprofundar as principais características que notabilizam esse antagonismo entre racionalidades econômica e laboral-protetiva. A partir daí, aclaradas as premissas atinentes aos diferentes pontos de vista que envolvem o tema e partindo para a apreciação em um plano constitucional mais abstrato, axiológico, o texto seguirá no sentido de perquirir, à luz de uma leitura moral (dworkiniana) do problema constitucional, o modo como o ponto de vista patrimonialista típico das categorias econômicas deverá se compatibilizar com a realização dos fins sociais atinentes à valorização do trabalho humano.  Ao final, proporemos que, no atual contexto democrático de direito, os interesses empresariais de flexibilização da tutela trabalhista, apesar de atuarem legitimamente mediante uma racionalidade econômica no sentido de minimizar custos e maximizar riquezas, devem ser limitados pelas diretrizes constitucionais que, a partir de um robusto aparato normativo de proteção da pessoa humana, evidenciam a predileção pela tutela do trabalhador frente aos interesses mercantis, sob pena de nos distanciarmos a passos largos do ideal de justiça e equidade.PALAVRAS-CHAVE: Direito Constitucional do Trabalho. Flexibilização. Racionalidade econômica. Valor social do trabalho. ABSTRACT: The flexibilization of labor rights is an issue in the economic reality of our country, especially in the context of the economic crisis we are experiencing. The objective of this work is to reflect on the compatibility between the economic reasoning, linked with the current proposals for relativization of labor legislation, and the legal frameworks from Constitutional Economic Order, especially the social value of human labor. Through a bibliographical research and constitutional and infraconstitutional normative analysis, a digression will be made first on the evolution of the labor protection legal system and the flexibilizing proposals in history. Once the historical friction between corporate interests and labor social protection is observed, this work will focus on deepening the main characteristics that distinguish this antagonism between economic and labor-protection rationalities. Clarifying the premises concerning the different points of view that involve the theme and starting for the appreciation in a more abstract, axiological constitutional plan, the text will follow in order to investigate how the patrimonialist viewpoint of the economic categories should be compatible with the social purposes related to the valorization of human work, based on a moral (Dworkinian) interpretation of the constitutional problem. In the end, we will propose that, in the current democratic context of law, the business interests in flexibilization of labor protection, although acting legitimately through economic rationality to minimize costs and maximize wealth, should be limited by the constitutional guidelines that, from a robust normative apparatus of human protection, evidences the predilection for the protection of the worker against the mercantile interests, otherwise we would distance ourselves from the ideal of justice and equity.KEYWORDS: Constitutional Labor Law. Flexibilization. Economic rationality. Social value of labor. Submetido em: 31-03-2017Aprovado em: 14-07-201

Penetrating injury to the chest by an attenuated energy projectile: a case report and literature review of thoracic injuries caused by "less-lethal" munitions

We present the case of a patient who sustained a penetrating injury to the chest caused by an attenuated energy rubber bullet and review the literature on thoracic injuries caused by plastic and rubber "less-lethal" munitions. The patient of this report underwent a right thoracotomy to extract the projectile as well as a wedge resection of the injured lung parenchyma. This case demonstrates that even supposedly safe riot control munition fired at close range, at the torso, can provoke serious injury. Therefore a thorough investigation and close clinical supervision are justified

Hyperoside Supplementation in Preservation Media Surpasses Vitamin C Protection Against Oxidative Stress-Induced Damages in Human Spermatozoa

Background/Aims: Oxidative Stress (OS) is reported as one of the main causes of male infertility. Infertile couples often resort to assisted reproductive technology (ART) to achieve parenthood. However, preparation for ART protocols increases the exposer of gametes to OS. Thus, it is crucial to find suitable preservation media that can counteract the OS-induced damages in spermatozoa. In this work, we tested and compared the efficiency of vitamin C (VC) and hyperoside (HYP) as potential antioxidant supplements for sperm preservation media. Methods: We evaluated the cytotoxicity of HYP (0, 5, 50, 100, and 500 µM) in spermatozoa. After incubation of sperm cells with VC (600 µM) and HYP (100 and 500 µM), in the presence and absence of H2O2 (300 µM), the following parameters were assessed: total sperm motility and vitality, OS biomarkers expression, total antioxidant capacity (TAC) of the media, percentage of DNA fragmentation, mitochondrial membrane potential (MMP), and metabolite quantification of the media by proton nuclear magnetic resonance (1H-NMR). Results: The supplementation with VC (600 µM) and HYP (100 and 500 µM) did not induce any deleterious effects to the physiology and metabolism of the spermatozoa, after 1-hour of treatment. In the presence of H2O2 (300 µM), both VC and HYP were able to prevent some of the deleterious effects of H2O2 in sperm, which were represented by an increase in sperm motility, a decrease in DNA fragmentation, and a decreasing trend in lipid peroxidation levels. However, these antioxidants were not able to prevent the decrease of MMP associated with H2O2 treatment, nor were able to prevent the conversion of pyruvate into acetate (a reaction promoted by H2O2). Conclusion: The supplementation of sperm preservation media with VC and HYP could be beneficial for the preservation of sperm physiology. From the antioxidant conditions tested, the supplementation of media with HYP (100 µM) demonstrated the best results regarding sperm preservation, evidencing the higher antioxidant capacity of HYP compared to VC. Nevertheless, none of the antioxidants used was able to prevent the metabolic alterations promoted by H2O2 in spermatozoa.This work was supported by Fundação para a Ciência e a Tecnologia - FCT to Sara C. Pereira (2021.05487.BD); David F. Carrageta (SFRH/BD/136779/2018); Marco G. Alves (IFCT2015 and PTDC/MEC-AND/28691/2017); LAQV-REQUIMTE (UIDB/50006/2020); UMIB (UIDB/00215/2020, and UIDP/00215/2020); ITR - Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020). Pedro F. Oliveira was funded by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., under the Scientific Employment Stimulus - Institutional Call - reference CEECINST/00026/2018

Propriétés psychométriques de l’échelle de satisfaction des cours académiques (ESCA) chez les étudiants universitaires brésiliens

Academic satisfaction has been studied from different perspectives that considerate distinct ways of measurement. However, the plurality of evaluated facets prevents a more parsimonious assessment of the general students’ academic satisfaction. In the article, we aimed to provide psychometric evidence of the validity and reliability for the AMSS in Brazil in two studies (N = 893). In Study 1, an exploratory factor analysis and item parameters (Item Response Theory) support the one-factor solution and the suitability of the six items. Moreover, evidence for factorial invariance across gender and convergent validity with the PANAS and with the SWLS was also presented in Study 2. In conclusion, the present paper provides evidence of the adequacy of the AMSS to evaluate global satisfaction with the academics course in Brazil.Propiedades psicométricas de la Escala de Satisfacción del Curso Académico (ESCA) en estudiantes universitarios brasileños La satisfacción académica ha sido estudiada bajo diferentes perspectivas, produciendo dife- rentes formas de medición. Sin embargo, la pluralidad de facetas evaluadas impide una evaluación más parsimoniosa de la satisfacción académica de los estudiantes en general. En este artículo, objetivamos proporcionar evidencias psicométricas de la validez y con- fiabilidad para el ESCA en Brasil en dos estudios (N = 893). En el Estudio 1, un análisis factorial exploratorio y los parámetros de los ítems (Teoría de Respuesta al Item) soportan la solución unifatorial y la adecuación de los seis ítems. Además, se presentaron evidencias de invariancia factorial entre género y validez convergente con el PANAS y con el ESV en el Estudio 2. En conclusión, este estudio proporciona evidencias de la adecuación de la ESCA para evaluar la satisfacción global con el curso académico en Brasil.A satisfação acadêmica tem sido estudada sob diferentes perspectivas que contemplam formas distintas de mensuração. Entretanto, a pluralidade de facetas avaliadas impede uma avaliação mais parcimoniosa da satisfação acadêmica dos estudantes em geral. O presente estudo tem por objetivo fornecer evidências psicométricas da validade e confiabilidade para o ESCA no Brasil em dois estudos (N = 893). No Estudo 1, uma análise fatorial exploratória e os parâmetros dos itens (Teoria de Resposta ao Item) suportam a solução unifatorial e a adequação dos seis itens. Além disso, foram apresentadas evidências de invariância fatorial entre gênero e validade convergente com o PANAS e com o ESV no Estudo 2. Em con- clusão, este estudo fornece evidências da adequação da ESCA para avaliar a satisfação global com o curso acadêmico na versão em português.La satisfaction académique a été étudiée sous différentes perspectives qui envisagent différentes formes de mesure. Cependant, la pluralité des facettes évaluées empêche une évaluation plus parcimonieuse de la satisfaction académique des étudiants en général. La pré- sente étude vise à fournir des preuves psychométriques de validité et de fiabilité pour ESCA au Brésil dans deux études (N = 893). Dans l’étude 1, une analyse factorielle exploratoire et les paramètres d’item (Théorie de la réponse à l’item) corroborent la solution à un facteur et l’adéquation des six items. En outre, nous avons présenté des preuves d’invariance factorielle entre le sexe et la validité convergentes avec PANAS et ESV dans l’étude 2. En conclusion, cette étude fournit des preuves de l’aptitude de l’ESCA à évaluer la satisfaction générale à l’égard du cours universitaire dans la version portugaise