IRE1α deficiency promotes tumor cell death and eIF2α degradation through PERK dipendent autophagy

Sensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end, we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient cells, by pharmacological inhibition with 4μ8 C or down-regulation by specific siRNA. We show that either type of IRE1α deficiency affects eIF2α expression and causes cell death increase. GSK2606414, a PERK inhibitor, and PERK specific siRNA prevent eIF2α down-regulation and restore cell survival. Degradation of this protein is due to autophagy, as it is prevented by bafilomycin and not by proteasome inhibition. Furthermore, activation of the autophagy flux is PERK dependent. Also the Cathepsin B inhibitor CA074 prevents eIF2α from degradation and reduces cell death. Altogether, these results show that IRE1α deficiency in ER stressed cells leads to an unexpected decrease of eIF2α, an important molecule for protein translation, through PERK dependent autophagy. Thus, IRE1/XBP1 inhibitors may represent a feasible strategy for tumor therapy, while PERK inhibitors may vanish the goal

Abordaje endodóntico de reabsorción comunicante

La reabsorción radicular interna es un proceso patológico que implica la destrucción progresiva de dentina intraradicular y túbulos dentinarios a lo largo de los tercios apical y medio de las paredes radiculares como resultado de actividad clástica.Fil: Aguilar Storniolo, Carla Gabriela. Universidad Nacional de Cuyo. Facultad de Odontología

Characterization of Wetting Front Geometry and Fluid Migration in the Vadose Zone Using Surface Time-Lapse Seismic First-Arrival Tomography

Characterizing and quantifying vadose zone parameters and processes are critical for assessing environmental, agricultural, and engineering problems. The shallow subsurface is essential to the geologic and hydrologic cycles because it supports agriculture and ecosystems, influences water resources, and acts as a repository for contaminants. Fluid migration in the vadose zone is dependent on a number of soil characteristics (e.g. soil type and saturation). Quantifying parameters is often the primary goal of hydrological fluid-flow investigations; however, the values calculated can be misrepresentative of the subsurface due to anisotropic features. Hydraulic conductivity (K), the most common quantitative parameter used to describe fluid flow through a porous medium, is complicated in the vadose zone due to spatial and temporal variations at many scales. Many in-situ methods for calculating K (i.e. constant head permeameter method) use surface measurements to quantify subsurface fluid flow. However, the geometry and distribution of the fluid migrating through the subsurface is not determinable from surface measurements, and therefore these techniques may not provide a comprehensive understanding of field-scale fluid flow. In this study, a more robust non-invasive method to image a migrating wetting front in the vadose zone is developed using time-lapse seismic first-arrival tomography (TLSFT). The TLSFT method is based on the concept that variations in seismic compressional wave (P-wave) arrival times are used as a proxy for the relative saturation changes due to an advancing wetting front generated from surface infiltration. Two constant flux applicator infiltration experiments were conducted at the East Tennessee Research and Education Center B-4 plot, while simultaneously collecting TLSFT data to image a migrating wetting front. The TLSFT infiltration method successfully images a migrating wetting front through the vadose zone at different time steps to visually characterize the geometry and distribution of water. Calculated K values using TLSFT infiltration data with an empirical formula are within one to two orders of magnitude of calculated K from an Amoozemeter experiment and known K of the Sequatchie soil series at the B-4 plot. TLSFT calculated ranges of K values are reasonable when considering the spatial and temporal extent of K at a single site

West Nile Virus Encephalitis in a Patient with Neuroendocrine Carcinoma

Importance. Oftentimes, when patients with metastatic cancer present with acute encephalopathy, it is suspected to be secondary to their underlying malignancy. However, there are multiple causes of delirium such as central nervous system (CNS) infections, electrolyte abnormalities, and drug adverse reactions. Because West Nile Virus (WNV) neuroinvasive disease has a high mortality rate in immunosuppressed patients, a high index of suspicion is required in patients who present with fever, altered mental status, and other neurological symptoms. Observations. Our case report details a single patient with brain metastases who presented with unexplained fever, encephalopathy, and new-onset tremors. Initially, it was assumed that his symptoms were due to his underlying malignancy or seizures. However, because his unexplained fevers persisted, lumbar puncture was pursued. Cerebrospinal fluid analysis included WNV polymerase chain reaction and serologies were ordered which eventually led to diagnosis of WNV encephalitis. Conclusions and Relevance. Patients with metastatic cancer who present with encephalopathy are often evaluated with assumption that malignancy is the underlying etiology. This can lead to delays in diagnosis and possible mistreatment. Our case highlights the importance of maintaining a broad differential diagnosis and an important diagnostic consideration of WNV encephalitis in patients with cancer

Gênero e raça na diplomacia brasileira : uma análise dos tratados internacionais que promovem a igualdade

Trabalho de Conclusão de Curso (graduação)—Universidade de Brasília, Faculdade de Direito, 2017.O presente trabalho tem como objetivo analisar a posição do Brasil em relação aos tratados internacionais que promovem a igualdade racial e de gênero, tendo como objeto de análise o corpo diplomático brasileiro. Devido à exclusão das mulheres e das pessoas negras das garantias previstas na Declaração Universal dos Direitos Humanos, esses grupos se organizaram para que suas demandas fossem cumpridas. Como resultado, eles ganharam a formalização dos direitos através de tratados internacionais aos quais o Brasil é parte. Reconhecendo a importância da presença de mulheres e pessoas negras na representação do país no exterior para a construção do direito internacional, investigo a composição racial e de gênero do Itamaraty, bem como as medidas institucionais tomadas para enfrentar as desigualdades encontradas. Embora o Brasil tenha se comprometido internacionalmente a se esforçar para mudar esse cenário, mulheres e pessoas negras permanecem sub-representados no corpo diplomático brasileiro, o que reflete as bases patriarcais e coloniais do nosso Estado.This study aims to analyze Brazil's position in relation to international treaties that promote racial and gender equality, having as object of analysis the Brazilian diplomatic corps. Due to the exclusion of women and black people from the guarantees provided for in the Universal Declaration of Human Rights, such groups organized themselves in order to have their demands supplied. As a result, they won the formalization of rights through international treaties to which Brazil is a State party. Recognizing the importance women and black people’s presence in the country's representation abroad for international law, I investigate the racial and gender composition of the Itamaraty, as well as the institutional measures taken to address the inequalities encountered. Although Brazil has committed itself internationally to change this scenario, women and black people remain underrepresented in the Brazilian diplomatic corps, which reflects the patriarchal and colonial bases of our State

A humanização do cuidado na ótica das equipes da estratégia de saúde da família de um município do interior paulista, Brasil

This study analyzes the understanding of professionals composing teams of the Family Health Strategy concerning humanization of care. This qualitative survey was carried out in a city in the interior of São Paulo through interviews with 20 professionals. The data analysis method used was Interpretation of Meanings based on the hermeneutic-dialectic perspective. The meaning of humanization according to the interviewed professionals includes an enlarged view, respect for ethical principles and facilitated access. The difficulties refer to the lack of prepared professionals, excessive demand and deficiencies in service organization. The professionals propose to educate and qualify professionals, make activities adequate given the professionals' roles and improve the organization of services. The professionals demonstrate understanding of the meaning of humanization and acknowledge the need to cope with difficulties.Este estudio tuvo como objetivo analizar la comprensión referente a la humanización del cuidado a partir de la perspectiva de profesionales que componen los equipos de la Estrategia de Salud de la Familia. Se trata de estudio cualitativo, realizado en un municipio del interior del estado de Sao Paulo, a partir de entrevistas con 20 profesionales. En el análisis de los datos fue utilizado el método de interpretación de los sentidos, basado en la perspectiva hermenéutica-dialéctica. El significado de la humanización para los profesionales entrevistados comprende una perspectiva ampliada, que incluye principios éticos y la facilidad para acceder al cuidado. Las dificultades se refieren a la falta de profesionales preparados, excesiva demanda y deficiencias en la organización del servicio. Los profesionales presentaron como propuesta formar y calificar profesionales, adecuar las actividades al papel profesional y mejorar la organización de los servicios. Los profesionales demuestran comprender el significado de la humanización y reconocen la necesidad de enfrentar las dificultades.Este estudo teve como objetivo analisar a compreensão referente à humanização do cuidado, sob a ótica de profissionais que compõem as equipes da Estratégia de Saúde da Família. Trata-se de estudo qualitativo, realizado em um município do interior paulista, a partir de entrevistas com 20 profissionais. Na análise dos dados, foi utilizado o método de interpretação de sentidos, baseado na perspectiva hermenêutico-dialética. O significado da humanização, para os profissionais entrevistados, compreende olhar ampliado, respeito aos princípios éticos e facilitação ao acesso. As dificuldades se referem à falta de profissionais preparados, excessiva demanda e deficiências na organização do serviço. Eles apresentaram, como proposta, formar e qualificar profissionais, adequar as atividades ao papel profissional e melhorar a organização dos serviços. Os profissionais demonstram compreender o significado da humanização e reconhecem a necessidade de enfrentamento das dificuldades

Cardiovascular risk protection from the Mediterranean diet and olive oil. A transcriptomic update in humans

This review highlights the human studies that explore the benefits of the Mediterranean diet and olive oil, based on gene expression analysis. We summarized consistent human transcriptomic studies on cardiovascular risk, based on TMD and olive oil interventions, with real life doses and conditions. A literature review was carried out leading up to February 2016. The results show that the TMD, specially supplemented with virgin olive oil, produces beneficial changes in the transcriptomic response of relevant genes in cardiovascular risk such as CAT, GPX1 and SIRT2. p65 and MCP-1, IL1B, IL6, CXCL1, INF-γ, ARHGAP15 and IL7R, which are involved in inflammation; and ABCA1, SR-B1, PPARBP, PPARα, PPARγ, PPARδ, CD-36 and COX-1, which play an important role in cholesterol efflux. The available data illustrate a transcriptomic effect on atherosclerosis, inflammation and oxidative stress pathways as well as the mentioned genes

Plano de negócio : Somos Sol

Este trabalho tem por objetivo a elaboração de um plano de negócios para uma empresa de festas e eventos. O plano contêm todos os itens necessários para o entendimento, formação e viabilidade do empreendimento. Na primeira etapa são revisados conceitos relativos ao empreendedorismo, estrutura do plano de negócios e planejamento estratégico que servirão de suporte para o desenvolvimento do plano. Na segunda etapa, os conceitos e a estrutura são aplicados e é realizado o plano de negócios. Há a descrição da empresa, sua missão e visão, análise de mercado, objetivos e metas, posicionamento estratégico e análise financeira. Por fim, conclui-se que o negócio é viável como segunda fonte de renda até o momento em que seja atingido as metas estabelecidas, nesse momento será possível a disponibilidade em tempo integral de todos os sócios.This work aims to prepare a business plan for an event company. The plan contains all the items necessary for the understanding, formation and viability of the project. In the first stage, concepts related to entrepreneurship, the structure of the business plan and strategic planning that will support the development of the plan are reviewed. In the second stage, the concepts and structure are applied and the business plan is made. There is a description of the company, its mission and vision, market analysis, objectives and goals, strategic positioning and financial analysis. Finally, it is concluded that the business is viable as a second source of income until the established goals are reached, at that moment, full-time availability of all partners will be possibl

CURRENT TOPICS IN LOCOMOTION PHYSIOLOGY: A) MUSCLE EFFICIENCY IN HEAVILY LOADED GRADIENT WALKING AND B) HEART RATE OFF-KINETICS AS A PREDICTOR OF VO2MAX

The human locomotion has been constantly analysed from both bioenergetics and biomechanical point of views (Saibene & Minetti, 2003; Cavagna, 2010). Since earliest times, hunting for food and escaping from predators already has proven how important is to comprehend this complex engineering that is our locomotor machine. Gradient locomotion has been investigated in the past, and the concept of the optimum gradient for walking, running and mountain paths are well known in the literature. The existence of an optimum gradient is based on the different partitioning between positive and negative mechanical work (that mirrors concentric and eccentric muscular activity) and the related metabolic demand. In the literature, the ratio between negative and positive work efficiency during unloaded locomotion was found to be 5/1. The purpose of this new study is to analyse the mechanical, metabolic and electromyography parameters during gradient loaded walking in order to understand how an extra-load can affect locomotion and especially the efficiency of positive and negative work. Still, another important topic referred to the human locomotion physiology is about the cardiovascular system. Related to this, oxygen uptake (V'O2) refers to the product of cardiac output and the volume of oxygen extracted from the blood, and its maximal value (V'O2peak) strengthen the maximal capacity of the cardiovascular system to provide O2 to muscle cells during continued exercise, being the most widely used measure of physical fitness (Plasqui & Westerterp, 2005; Koeneman et al., 2011). Although there is a large genetic component, it is mainly determined by a person\u2019s activity level, and inversely related to several health outcomes such as cardiovascular disease (Daanen et al., 2012). Besides of heart rate (HR) control and its relationship with V'O2, the HR recovery (off transient, after exercise) has received more attention by current researchers (Myers et al., 2007; Dupuy et al., 2012; Haddad et al., 2012). The rate of decline in HR following termination of exercise, which is regulated by the autonomic nervous system and thereby, provides information concerning sympathetic and parasympathetic activity (Daanen et al., 2012). In general, the more rapid the HR recovery, the better the fitness (Daanen et al., 2012; Buchheit, 2014). While exercise-training studies usually report HR values at a given time during the recovery period (Daanen et al., 2012), in most clinical studies, HR recovery is defined as the difference between HR at the end of exercise and HR at a given time during the recovery period (Otsuki et al., 2007; Dupuy et al., 2012). Moreover, in some studies a mono-exponential model fit the HR off-kinetics to derive global parameters of HR recovery kinetics such as the time constant or the asymptotic value (Stanley et al., 2013; Peinado et al., 2014). Based on these results and the growing interest in new smart devices for health monitoring, here we aimed to estimate V'O2peak from a short test (60 m) with variables that can be detected by the smart sensors. We ask to 25 healthy subjects to perform a maximal sprint over 60-m. Beat-by-beat HR was recorded by a chest belt during the whole test including resting period before and recovery post sprint. (n = 25). HR off kinetics was fitted by a mono-exponential function and tau value was calculated in order to obtain a velocity of HR decrement post exercise. V'O2peak was then estimate with a multiple regression analysis: V'O2peak = 7.46 19vtest + 261.4 19voff - 0.19 19 06HR (R2= 0.65, p<0.001). Where vtest represents the velocity performed during the 60-m test, voff corresponds to the velocity of HR decreasing during off-transient (recovery phase), and " 06HR" is the difference of HR during on-transient of exercise and it is the difference between maximum and the resting value. This new equation does not aim to replace the laboratory-standard protocols for V'O2peak determination, but it can give an insight about fitness level to laymen that use smart devices for monitoring their physical activity. Whenever these new models (smart watches) would perform a beat-by-beat analysis this equation could be introduced to the software and give a first general estimate of the user's fitness level