Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

Since its discovery, several chemical modifications in the testosterone molecule have been done by pharmaceutical industry in order to improve its pharmacological effects, resulting in the creation of anabolic steroids (AS). Despite the therapeutic benefits, AS abuse has spread among elite and recreational athletes in the search for improvements on physical appearance and physical performance. Illicit use of anabolic AS has been correlated with several adverse effects, such as cardiovascular, endocrine, reproductive, and neurobehavioral dysfunctions. Recently, declines on cognitive and mnemonic performance have been demonstrated clinically and experimentally. Experimental studies have demonstrated that these neurological dysfunctions are correlated to spread neuronal apoptosis throughout important areas of the central nervous system (CNS), such as hippocampus and cortex. Several pathophysiological mechanisms have been linked to the AS-induced neurotoxicity, including redox imbalance and recruitment of pro-apoptotic downstream pathways. Furthermore, exposure to AS has arisen as a potential risk factor to the development of Alzheimer’s disease. Altogether, these evidences imply that AS abuse per se induces neurodegeneration and can aggravate the prognosis of neurodegenerative diseases

Adoption of Electronic Information System (SEI) by the Ministry of Justice: An assessment in the user perspective

Este estudo investiga a atitude de usuários em relação ao Sistema Eletrônico de Informações (SEI), adotado pelo Ministério da Justiça (MJ) do Brasil, baseando-se em dimensões de adoção de ecnologia segundo Moore e Benbasat (1991). Aplicaram-se questionários entre usuários do SEI (N=208), incluindo a verificação de evidências de validade da escala por análise fatorial exploratória. Como resultados, verificou-se que: há confiabilidade dos fatores e os itens das dimensões de vantagem relativa e compatibilidade compuseram um só fator; há atitude favorável ao SEI; grupos de usuários que utilizam o SEI há mais tempo diferiram em relação aos iniciantes quanto a vantagem relativa, compatibilidade e testabilidade do sistema; pessoas mais velhas valorizaram facilidade de uso e testabilidade, enquanto as mais jovens valorizam demonstrabilidade de resultados. O estudo recomenda reflexões sobre a variável vantagem relativa, por ter incorporado outro fator, e também sobre novas aplicações do instrumento em outros órgãos públicos adotantes do SEI.Este estudio investiga la actitud de los usuarios en relación con el Sistema Electrónico de Información (SEI), aprobado por el Ministerio de Justicia (MJ) de Brasil, basado en la tecnología de las dimensiones de adopción de acuerdo con Moore y Benbasat (1991). Fueron aplicados cuestionarios entre los usuarios de SEI (N = 208), incluyendo la verificación de validez de la escala mediante análisis factorial exploratorio. Como resultado, se encontró que: existe confiabilidad de las mediciones y los elementos de las dimensiones de ventaja relativa y compatibilidad se incluyeron un solo factor; hay actitud favorable a SEI; grupos de usuarios utilizando el SEI hace más tiempo diferían en relación a los principiantes en ventaja relativa, compatibilidad y capacidad de prueba del sistema; las personas mayores aprecian la facilidad de uso y la capacidad de prueba, mientras que los más jóvenes aprecian la demostrabilidad de resultados. El estudio recomienda reflexiones sobre las variables de ventaja relativa, mediante la incorporación de otro factor, y también sobre nuevas aplicaciones del instrumento en otros organismos públicos adoptantes del SEI.This study investigate the attitude of users regarding the Electronic Information System (SEI), adopted by the Ministry of Justice (MJ) of Brazil, based on technology adoption dimensions according to Moore and Benbasat (1991). Questionnaires were applied among users of SEI (N=208), including verification of scale validity evidences by exploratory factor analysis. The results include: the reliability of the factors and the items of the dimensions of relative advantage and compatibility merged in only one factor; there is favorable attitude toward the SEI; user groups using the SEI for a longer period differ in relation to beginners, regarding relative advantage, compatibility and trialability of the system; older people valued ease of use and trialability, while younger ones valued result demonstrability. The study recommends reflections concerning to relative advantage variable, which incorporated other factor, and also indicates new applications of the instrument in other public organizations that adopt SEI.Revista do Serviço Público - RSP, v. 69, n. 4, p. 1015-1036ComunicaçãoGestão PúblicaTransparência, Controle e ParticipaçãoISSN Eletrônico: 2357-8017ISSN Impresso: 0034-924

Sclerostin Stimulates Osteocyte Support of Osteoclast Activity by a RANKL-Dependent Pathway

Sclerostin is a product of mature osteocytes embedded in mineralised bone and is a negative regulator of bone mass and osteoblast differentiation. While evidence suggests that sclerostin has an anti-anabolic role, the possibility also exists that sclerostin has catabolic activity. To test this we treated human primary pre-osteocyte cultures, cells we have found are exquisitely sensitive to sclerostin, or mouse osteocyte-like MLO-Y4 cells, with recombinant human sclerostin (rhSCL) and measured effects on pro-catabolic gene expression. Sclerostin dose-dependently up-regulated the expression of receptor activator of nuclear factor kappa B (RANKL) mRNA and down-regulated that of osteoprotegerin (OPG) mRNA, causing an increase in the RANKL∶OPG mRNA ratio. To examine the effects of rhSCL on resulting osteoclastic activity, MLO-Y4 cells plated onto a bone-like substrate were primed with rhSCL for 3 days and then either mouse splenocytes or human peripheral blood mononuclear cells (PBMC) were added. This resulted in cultures with elevated osteoclastic resorption (approximately 7-fold) compared to untreated co-cultures. The increased resorption was abolished by co-addition of recombinant OPG. In co-cultures of MLO-Y4 cells with PBMC, SCL also increased the number and size of the TRAP-positive multinucleated cells formed. Importantly, rhSCL had no effect on TRAP-positive cell formation from monocultures of either splenocytes or PBMC. Further, rhSCL did not induce apoptosis of MLO-Y4 cells, as determined by caspase activity assays, demonstrating that the osteoclastic response was not driven by dying osteocytes. Together, these results suggest that sclerostin may have a catabolic action through promotion of osteoclast formation and activity by osteocytes, in a RANKL-dependent manner

Profile of the elderly who naps

This study aimed to characterize the elderly who naps according to sociodemographic characteristics and frailty. A descriptive, cross-sectional study part of the multicenter project Frailty in the Elderly Brazilians. We evaluated 1,866 elderly people using a sociodemographic questionnaire. The frailty was assessed using the phenotype proposed by Fried. The data were analyzed with descriptive statistics. The results showed that the profile of the elderly who naps consists predominantly of women, married, retired, pre-frail, with an average age of 73 years, four years of study, with monthly family income of 3.9 minimum salary, with 4,4 children who were living with them only. The elderly reported napping on average 5.9 days per week, lasting 53.5 minutes per nap. Knowing the profile of the elderly who naps contributes to health professionals in the development of actions in relation to sleep problems of the frail/pre-frail elderly, preventing, minimizing or solving these problems.Esse estudo objetivou caracterizar os idosos que cochilam segundo as características sociodemográficas e de fragilidade. Estudo descritivo, transversal, recorte do projeto multicêntrico Fragilidade em Idosos Brasileiros. Foram avaliados 1.866 idosos utilizando-se questionário sociodemográfico. A fragilidade foi avaliada usando o fenótipo proposto por Fried. Os dados foram tratados com estatística descritiva. Os resultados apontaram que o perfil do idoso que cochila foi constituído predominantemente por mulheres, casadas, aposentadas, pré-frágeis, com média de idade de 73 anos, quatro anos de estudo, renda familiar mensal de 3,9 salários mínimos, com 4,4 filhos e que residiam apenas com eles. Os idosos relataram cochilar em média 5,9 dias por semana, com duração de 53,5 minutos por cochilo. Conhecer o perfil do idoso que cochila contribui para os profissionais de saúde desenvolverem ações em relação aos problemas de sono dos idosos frágeis/pré-frágeis, prevenindo, minimizando ou resolvendo esses problemas.El objetivo de este estudio fue caracterizar a adultos mayores que dormitan según las características socio-demográficas y de fragilidad. Estudio descriptivo, transversal, un recorte del proyecto multicéntrico Fragilidad en los adultos mayores brasileños . Fueron evaluados 1866 adultos mayores mediante el cuestionario socio-demográfico. La fragilidad se evaluó mediante el fenotipo propuesto por Fried. Los datos fueron procesados mediante estadística descriptiva. Los resultados mostraron que el perfil del anciano que dormita fue constituido principalmente por mujeres, casadas, jubiladas, pre-frágiles, siendo el promedio de edad de 73 años, cuatro años de educación, con ingreso familiar mensual de 3,9 sueldos mínimos, con 4,4 hijos, y que vivían sólo con sus hijos. Los adultos mayores reportaron dormitar en promedio 5,9 días por semana, con duración de 53,5 minutos por siesta. Conocer el perfil de los adultos mayores que dormitan contribuye para que los profesionales de la salud desarrollen acciones relacionadas con los problemas de sueño de los adultos mayores frágiles/pre-frágiles, previniendo, minimizando o resolviendo estos problemas.1345135

The gut microbiome and metabolome of two riparian communities in the Amazon

During the last decades it has become increasingly clear that the microbes that live on and in humans are critical for health. The communities they form, termed microbiomes, are involved in fundamental processes such as the maturation and constant regulation of the immune system. Additionally, they constitute a strong defense barrier to invading pathogens, and are also intricately linked to nutrition. The parameters that affect the establishment and maintenance of these microbial communities are diverse, and include the genetic background, mode of birth, nutrition, hygiene, and host lifestyle in general. Here, we describe the characterization of the gut microbiome of individuals living in the Amazon, and the comparison of these microbial communities to those found in individuals from an urban, industrialized setting. Our results showed striking differences in microbial communities from these two types of populations. Additionally, we used high-throughput metabolomics to study the chemical ecology of the gut environment and found significant metabolic changes between the two populations. Although we cannot point out a single cause for the microbial and metabolic changes observed between Amazonian and urban individuals, they are likely to include dietary differences as well as diverse patterns of environmental exposure. To our knowledge, this is the first description of gut microbial and metabolic profiles in Amazonian populations, and it provides a starting point for thorough characterizations of the impact of individual environmental conditions on the human microbiome and metabolome

Occurrence of late postoperative knee and hip arthroplasty postoperative complications / Ocorrência de complicações no pós-operatório tardio de artroplastia de joelho e quadril

Objetivo: avaliar a prevalência de complicações no pós-operatório e sua associação com variáveis sociodemográficas e clínicas. Métodos: Trata-se de um estudo descritivo, de seguimento prospectivo, realizado com 99 pacientes de um hospital de ensino. Os participantes foram selecionados por amostragem intencional (referencia) e seguidos por 30 dias após a alta do hospital. Realizou-se análises descritivas, univariadas e bivariadas Resultados: 32 (32,3%) pacientes desenvolveram ao menos uma complicação, sendo que 10 (10,1%) desenvolveram mais de uma complicação num seguimento de 30 dias. Dor (31; 31,3%) e Infecção (12; 12,1%) foram as complicações mais prevalentes. Identificou-se associação estatística entre o desfecho clinico dos pacientes submetidos a cirurgia de joelho e quadril e a presença de complicações no pós-operatório (p<0,001). Conclusão: A ocorrência de complicações no pós-operatório de artroplastia de joelho e quadril num seguimento de 30 dias foi elevada, com destaque para a dor e infecção local.

When an Intramolecular Disulfide Bridge Governs the Interaction of DUOX2 with Its Partner DUOXA2

Aims: The dual oxidase 2 (DUOX2) protein belongs to the NADPH oxidase (NOX) family. As H2O2 generator, it plays a key role in both thyroid hormone biosynthesis and innate immunity. DUOX2 forms with its maturation factor, DUOX activator 2 (DUOXA2), a stable complex at the cell surface that is crucial for the H2O2-generating activity, but the nature of their interaction is unknown. The contribution of some cysteine residues located in the N-terminal ectodomain of DUOX2 in a surface protein?protein interaction is suggested. We have investigated the involvement of different cysteine residues in the formation of covalent bonds that could be of critical importance for the function of the complex. Results: We report the identification and the characterization of an intramolecular disulfide bond between cys-124 of the N-terminal ectodomain and cys-1162 of an extracellular loop of DUOX2, which has important functional implications in both export and activity of DUOX2. This intramolecular bridge provides structural support for the formation of interdisulfide bridges between the N-terminal domain of DUOX2 and the two extracellular loops of its partner, DUOXA2. Innovation: Both stability and function of the maturation factor, DUOXA2, are dependent on the oxidative folding of DUOX2, indicating that DUOX2 displays a chaperone-like function with respect to its partner. Conclusions: The oxidative folding of DUOX2 that takes place in the endoplasmic reticulum (ER) appears to be a key event in the trafficking of the DUOX2/DUOXA2 complex as it promotes an appropriate conformation of the N-terminal region, which is propitious to subsequent covalent interactions with the maturation factor, DUOXA2. Antioxid. Redox Signal. 23, 724?733.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140308/1/ars.2015.6265.pd

Soluble Rank Ligand Produced by Myeloma Cells Causes Generalised Bone Loss in Multiple Myeloma

Patients with multiple myeloma commonly develop focal osteolytic bone disease, as well as generalised osteoporosis. The mechanisms underlying the development of osteoporosis in patients with myeloma are poorly understood. Although disruption of the RANKL/OPG pathway has been shown to underlie formation of focal osteolytic lesions, its role in the development of osteoporosis in myeloma remains unclear. Increased soluble RANKL in serum from patients with myeloma raises the possibility that this molecule plays a key role. The aim of the present study was to establish whether sRANKL produced by myeloma cells contributes directly to osteoporosis. C57BL/KaLwRij mice were injected with either 5T2MM or 5T33MM murine myeloma cells. 5T2MM-bearing mice developed osteolytic bone lesions (p<0.05) with increased osteoclast surface (p<0.01) and reduced trabecular bone volume (p<0.05). Bone volume was also reduced at sites where 5T2MM cells were not present (p<0.05). In 5T2MM-bearing mice soluble mRANKL was increased (p<0.05), whereas OPG was not altered. In contrast, 5T33MM-bearing mice had no changes in osteoclast surface or trabecular bone volume and did not develop osteolytic lesions. Soluble mRANKL was undetectable in serum from 5T33MM-bearing mice. In separate experiments, RPMI-8226 human myeloma cells were transduced with an human RANKL/eGFP construct, or eGFP alone. RPMI-8226/hRANKL/eGFP cells, but not RPMI-8226/eGFP cells, stimulated osteoclastic bone resorption (p<0.05) in vitro. Sub-cutaneous injection of NOD/SCID mice with RPMI-8226/hRANKL/eGFP or RPMI-8226/eGFP cells resulted in tumour development in all mice. RPMI-8226/hRANKL/eGFP-bearing mice exhibited increased serum soluble hRANKL (p<0.05) and a three-fold increase in osteoclast number (p<0.05) compared to RPMI-8226/eGFP-bearing mice. This was associated with reduced trabecular bone volume (27%, p<0.05), decreased trabecular number (29%, p<0.05) and increased trabecular thickness (8%, p<0.05). Our findings demonstrate that soluble RANKL produced by myeloma cells causes generalised bone loss, suggesting that targeting RANKL may prevent osteoporosis in patients with myeloma

Análise prospectiva com ênfase científica e tecnológica do tucum (Bactris setosa Mart) como possível bioadsorvente

Os bioadsorventes à base de biomassa são de baixo custo e apresentam excelentes resultados para remoção de contaminantes orgânicos. O tucum (Bactris setosa) é uma alternativa promissora para aplicação como bioadsorvente, especialmente, pela larga disponibilidade e baixo custo. O presente trabalho teve como objetivo mapear as produções científicas e tecnológicas relacionadas à B. setosa, avaliando suas potencialidades. Foi realizada uma busca nas principais bases de dados de patentes e periódicos científicos nacionais e internacionais, nos últimos 20 anos. A busca encontrou 74 patentes e 49 artigos. O maior número de patentes depositadas foi em 2019. EUA apareceu como o maior depositante, seguido pela Coréia e China. A área de Agricultura é que mais publica sobre o tema, o Brasil foi o país com mais publicações, seguido pelo Reino Unido. Em 2018 e 2019 houve intensa produção sobre o tema. Os resultados evidenciaram a potencialidade tecnológica e científica da espécie para a indústria farmacêutica

EXERCÍCIO DE CORRIDA DE ALTA INTENSIDADE ALTERA A EXPRESSÃO DE THY-1 E ECTONUCLEOTIDASE NA SUPERFÍCIE DE LINFÓCITOS

O exercício agudo é um desafio a homeostase e após exercício físico intenso ocorre transiente linfopenia e imunossupressão. As moléculas de adesaão celular são expressas na superfície dos leucócitos e das células endoteliais, tendo um papel fundamental nas interações entre linfócito e endotélio. O objetivo do presente estudo foi analisar a expressão de CD73, CD90 e CD105 em leucócitos após corrida de alta intensidade. Dez homens jovens foram inscritos em uma corrida de 4 km e o sangue foi coletado 60 minutos antes, 5 minutos, 1, 3, 6 e 24 hs após a o exercício, para avaliação hematológica e determinação de marcadores de superfície celulares por citometria de fluxo. Foi utilizado o teste ANOVA de uma via com o teste de Dunnet's como post hoc para a análise estatística. Os dados foram considerados diferentes estatisticamente quando p0,05. Os leucócitos aumentaram 30% e os granulócitos 40 -- 70% após 6h de exercício físico. Linfopenia foi observada 1 h após o exercício, como esperado. Monócitos, eosinófilos e basófilos, e outros parâmetros hematológicos não se alteraram. Linfócitos T, linfócitos T helper e células citotóxicas aumentaram em resposta ao exercício. Linfócitos B e as células exterminadoras naturais (natural killers) aumentaram imediatamente após o exercício. A células CD73+ aumentaram somente imediatamente após o exercício e as células CD90+ diminuíram 24h após o exercício. Podemos concluir que a corrida de alta intensidade induziu a resposta clássica do sistema imuno-endócrino e é capaz de alterar o número de células CD73+ e CD90+