Influence Of The Degree Of Hydrolysis And Type Of Enzyme On Antioxidant Activity Of Okara Protein Hydrolysates

The objective of this work was to evaluate the antioxidant activity of protein hydrolysates obtained by the enzymatic hydrolysis of okara using an endopeptidase (Alcalase) and exopeptidase (Flavourzyme). The reaction was monitored by the pH-stat procedure in which five aliquots were collected during the hydrolysis by each enzyme, corresponding to different degrees of hydrolysis (DH). The antioxidant activities of the aliquots were evaluated by the ABTS, DPPH and FRAP methods. For the hydrolysates obtained using Alcalase, the antioxidant activities increased from: 68.6 to 99.5% (ABTS), 14.5 to 17.7% (DPPH) and 222.6 to 684.9 [iM Trolox (FRAP), when the DH varied from 0 to 33.6%. With respect to Flavourzyme, the results were: 67.2 to 88.2% (ABTS), 9.5 to 18.5% (DPPH) and 168.0 to 360.3 [µM Trolox (FRAP), when the DH increased up to 5.8%. The results showed that the protein hydrolysates had antioxidant capacities, which were influenced by the degree of hydrolysis and the type of enzyme. © 2016 Sociedade Brasileira de Ciencia e Tecnologia de Alimentos, SBCTA. All rights reserved.36237538

Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infection

Background In high-income countries, it is standard practice to give antibiotics to women with pre-term, pre-labour rupture of membranes (pPROM) to delay birth and reduce the risk of infection. In low and middle-income settings, where some 2 million neonatal deaths occur annually due to complications of pre-term birth or infection, many women do not receive antibiotic therapy for pPROM

Avaliação da qualidade de vida de médicos clínicos e cirurgiões

Objetivo: Avaliar a qualidade de vida (QV) dos profissionais da área médica de acordo com a especialidade escolhida (clínica ou cirúrgica). Métodos: Estudo transversal analítico, realizado em 2016, com médicos de clínicas e hospitais de Rio Verde, Goiás, Brasil. Utilizaram-se dois questionários: um sobre aspectos sociodemográficos e outro para avaliação da QV, o World Health Organization Quality of Life-Bref (WHOQOL-abreviado). Entregaram-se 287 questionários, sendo 144 respondidos. Dados comparativos dos domínios receberam análise ANOVA, MANOVA, MANCOVA, correlação de Pearson e regressão linear, considerando-se p˂0,05. Resultados: Encontrou-se média de idade de 37,7±10,09 anos e a maioria do sexo masculino (63,1%; n=91). O domínio físico foi, significantemente, melhor avaliado nos valores médios de QV pelo sexo masculino (p=0,002), assim como o domínio meio ambiente (p=0,031). Quando se comparou valores médios da QV e seus domínios de acordo com a atuação clínica e/ou cirúrgica dos médicos, não houve diferença significativa. Ao se comparar médicos plantonistas e não plantonistas, verificou-se que os domínios relação social (p=0,049), meio ambiente (p=0,001) e QV (p=0,024), independentes da carga horária, apresentaram piora no caso dos médicos plantonistas. Quanto maior o tempo de formado, maior a percepção do domínio meio ambiente (p=0,02). Sem diferença significativa quanto à faixa salarial. Conclusão: Não houve diferença na qualidade de vida global entre os médicos clínicos e cirurgiões avaliados, porém, quando comparado entre o sexo, o masculino obteve desempenho mais satisfatório nos domínios físico e meio ambiente. Evidenciou-se que a faixa salarial não influencia na qualidade de vida desses profissionais

Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and atherosclerosis

Aim To determine the role of NOTCH during the arterial injury response and the subsequent chronic arterial-wall inflammation underlying atherosclerosis. Methods and results We have generated a mouse model of endothelial-specific (Cdh5-driven) depletion of the Notch effector recombination signal binding protein for immunoglobulin kappa J region (RBPJ) [(ApoE$^{−/−}$); homozygous RBPJk conditional mice (RBPJ$^{flox/flox}$); Cadherin 5-Cre$^{ERT}$, tamoxifen inducible driver mice (Cdh5-Cre$^{ERT}$)]. Endothelial-specific deletion of RBPJ or systemic deletion of Notch1 in athero-susceptible ApoE$^{−/−}$ mice fed a high-cholesterol diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus. Intravital microscopy revealed decreased leucocyte rolling on the endothelium of ApoE$^{−/−}$; RBPJ$^{flox/flox}$; Cdh5-Cre$^{ERT}$ mice, correlating with a lowered content of leucocytes and macrophages in the vascular wall. Transcriptome analysis revealed down-regulation of proinflammatory and endothelial activation pathways in atherosclerotic tissue of RBPJ-mutant mice. During normal Notch activation, Jagged1 signalling up-regulation in endothelial cells promotes nuclear translocation of the Notch1 intracellular domain (N1ICD) and its physical interaction with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This N1ICD–NF-κB interaction is required for reciprocal transactivation of target genes, including vascular cell adhesion molecule-1. Conclusions Notch signalling pathway inactivation decreases leucocyte rolling, thereby preventing endothelial dysfunction and vascular inflammation. Attenuation of Notch signalling might provide a treatment strategy for atherosclerosis.This study was funded by grants SAF2013-45543R, RD12/0042/0005 (RIC) and RD12/0019/0003 (TERCEL) from the Spanish Ministry of Economy and Competitiveness (MINECO) to J.L.dlP, RD12/0042/0028 (RIC) to V.A. and RD12/0042/0053 (RIC) and SAF2012-40127 to J.M.G. M.N. held a Sara Borrell post-doctoral contract (CD09/00452) and D.M. holds a post-doctoral contract associated with grant RD12/0042/0005, both awarded by The Instituto de Salud Carlos III; B.M.P. holds a Juan de la Cierva post-doctoral contract (JCI-2010-06343). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro CNIC Foundation, and is a ‘Severo Ochoa’ Center of Excellence (MINECO award SEV-2015-0505).This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/cvr/cvw19

ANÁLISE DAS HABILIDADES SOCIAIS, ESTRESSE E SONOLÊNCIA DIURNA EM ESTUDANTES DE MEDICINA

Objetivo: Analisar as habilidades sociais, os níveis de estresse e de sonolência diurna em estudantes de Medicina em diferentes momentos da graduação. Métodos: trata-se de uma investigação do tipo descritiva transversal quantitativa, sendo a amostra não probabilística, discentes de todos períodos letivos da Faculdade de Medicina da Universidade de Rio Verde, Rio Verde, Goiás, Brasil. Os dados coletados foram idade, sexo, período letivo, além três questionários validados na literatura com os instrumentos: Inventario de Habilidades Sociais de Del Prette e Del Prette, Inventários de Estresse Percepcionado e Escala de Sonolência Diurna de Epworth. Os dados foram analisados no programa SPSS, versão 22.0, sendo submetidos a que verificou-se distribuição normal, utilizando demais testes paramétricos. Também realizou-se análise estatística descritiva, correlacionando os instrumentos. Por fim, foi verificado a confiabilidade interna do instrumento. Resultados: Existe um número significativo de estudantes de Medicina com um péssimo desempenho em habilidades sociais (59,2%), sendo estes associados a escores patológicos de sonolência diurna e altos níveis de estresse em mais da metade da população estudada, piorando com decorrer do curso. Conclusão: O desenvolvimento das habilidades sociais durante a graduação garante o aprimoramento das relações pessoais e profissionais, contribuindo para a formação integral do médico e uma prática médica mais competente e humana

ENGAGEMENT E QUALIDADE DO SONO E MAIS CONEXÕES DO BURNOUT ACADÊMICO.

Resumo: Objetivo: Deste estudo foi analisar a prevalência do engagement que condiz com sintomas positivos da síndrome de burnout  e correlacionar com a qualidade do sono e variáveis sociodemográficas. Métodos: Trata-se de um estudo transversal realizado na Universidade de Rio verde utilizando-se de um instrumento construído pelo próprio autor e o segundo instrumento UWES-S – Utrecht Work Engagement Scale-Student que mensura o e correlacionar com dados do instrumento sociodemográfico próprio juntamente com o instrumento PSQI- Pittsburgh Quality Sleep index que permite evidenciar alterações no sono. Resultados: Foram analisados 228 questionários de alunos da graduação agrupados em 4 grande áreas( Humanas, Saude, Exatas e Agrarias), verificou-se uma maior média 3,51 ±6,2 no grupo da saúde pelas as relação das medias pelo teste T-student sob a esfera “vigor” do UWES-S notou-se diferença estatística entre o sexo masculino (ρ=0,03), na comparação por areas com as  esfera do UWES-S houve diferenças nas esferas da “Dedicação” quando comparado as áreas de Saúde x Agrarias(p=0,00) e Saúde x Humanas, na esfera da “Absorção” observou-se diferença estatísticas quando comparado Saúde x Agrarias (p=0,00) e Saúde x Exatas ( p=0,04).Não houve diferença estatística quando comparado o PSQI com o demais dados. Conclusão: O engajamento como constructo é recente no Brasil. Seu conhecimento possibilitou um novo olhar sobre o contexto acadêmico,porém nescessita de  pesquisas adicionais para investigar como os diferentes fatores que afetam o desgaste do estudante e o envolvimento no estud

Human Hereditary Cardiomyopathy Shares a Genetic Substrate With Bicuspid Aortic Valve.

The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers.This study was supported by grants PID2019-104776RB-I00 and PID2020-120326RB-I00, CB16/11/00399 (CIBER CV) financed by MCIN/AEI/10.13039/501100011033, a grant from the Fundación BBVA (Ref. BIO14_298), and a grant from Fundació La Marató de TV3 (Ref. 20153431) to J.L.d.l.P. M.S.-A. was supported by a PhD contract from the Severo Ochoa Predoctor-al Program (SVP-2014-068723) of the MCIN/AEI/10.13039/501100011033. J.R.G.-B. was supported by SEC/FEC-INV-BAS 21/021. A.R. was funded by grants from MCIN (PID2021123925OB-I00), TerCel (RD16/0011/0024), AGAUR (2017-SGR-899), and Fundació La Marató de TV3 (201534-30). J.M.P.-P. was supported by RTI2018-095410-B-I00 (MCIN) and PY2000443 (Junta de Andalucía). B.I. was supported by the European Commission (H2020-HEALTH grant No. 945118) and by MCIN (PID2019-107332RB-I00). DO’R was sup-ported by the Medical Research Council (MC-A658-5QEB0) and KAMcG by the British Heart Foundation (RG/19/6/34387, RE/18/4/34215). The cost of this publication was supported in part with funds from the European Regional Devel-opment Fund. The Centro Nacional de Investigaciones Cardiovasculares is sup-ported by the ISCIII, the MCIN, and the Pro Centro Nacional de Investigaciones Cardiovasculares Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S) financed by MCIN/AEI/10.13039/501100011033. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising.S

Mechanisms of Hsp90 regulation

Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated