Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B.

Background & aims In chronic HBV infection, mitochondrial functions and proteostasis are dysregulated in exhausted HBV-specific CD8 T cells. To better characterise the potential involvement of deregulated protein degradation mechanisms in T cell exhaustion, we analysed lysosome-mediated autophagy in HBV-specific CD8 T cells. Bioactive compounds able to simultaneously target both mitochondrial functions and proteostasis were tested to identify optimal combination strategies to reconstitute efficient antiviral CD8 T cell responses in patients with chronic HBV infection. Methods Lysosome-mediated degradation pathways were analysed by flow cytometry in virus-specific CD8 T cells from patients with chronic HBV infection. Mitochondrial function, intracellular proteostasis, and cytokine production were evaluated in HBV-peptide-stimulated T cell cultures, in the presence or absence of the polyphenols resveratrol (RSV) and oleuropein (OLE) and their metabolites, either alone or in combination with other bioactive compounds. Results HBV-specific CD8 T cells from patients with CHB showed impaired autophagic flux. RSV and OLE elicited a significant improvement in mitochondrial, proteostasis and antiviral functions in CD8 T cells. Cytokine production was also enhanced by synthetic metabolites, which correspond to those generated by RSV and OLE metabolism in vivo, suggesting that these polyphenols may also display an effect after transformation in vivo. Moreover, polyphenolic compounds improved the T cell revitalising effect of mitochondria-targeted antioxidants and of programmed cell death protein 1/programmed cell death ligand 1 blockade. Conclusions Simultaneously targeting multiple altered intracellular pathways with the combination of mitochondria-targeted antioxidants and natural polyphenols may represent a promising immune reconstitution strategy for the treatment of chronic HBV infection. Lay summary In chronic hepatitis B, antiviral T lymphocytes are deeply impaired, with many altered intracellular functions. In vitro exposure to polyphenols, such as resveratrol and oleuropein, can correct some of the deregulated intracellular pathways and improve antiviral T cell function. This effect can be further strengthened by the association of polyphenols with antioxidant compounds in a significant proportion of patients. Thus, the combination of antioxidants and natural polyphenols represents a promising strategy for chronic hepatitis B therapy

Estudo comparativo entre a Escala de Equilíbrio de Berg, o Teste Timed Up & Go e o Índice de Marcha Dinâmico quando aplicadas em idosos hígidos

Os distúrbios do equilíbrio compõem um dos fatores etiológicos centrais das quedas e da instabilidade em idosos, podendo levar a incapacidade funcional e dependência e, por isso vêm sendo utilizados como marcadores de fragilidade. Considerando que a prevenção e a reabilitação do declínio do equilíbrio em idosos requerem o desenvolvimento de protocolos de pesquisa adequados para se medir a função do equilíbrio, este trabalho teve como objetivo analisar e comparar a eficácia de três instrumentos de avaliação utilizados para identificar o risco de queda em idosos. Para isso, a Escala de equilíbrio de Berg (EEB), o Teste Timed Up & Go (TUG) e o Índice de Marcha Dinâmico (IMD) foram aplicados em sete idosos hígidos. A análise dos resultados revelou que as escalas utilizadas são de fácil aplicação e entendimento, não havendo necessidade de treinamento do avaliador. No entanto, como as três escalas avaliam aspectos distintos, foi possível identificar, na população avaliada, risco de queda aumentado em quatro idosos apenas por meio do IMD.Balance disorders are one of the central etiological factors of falls and instability in the elderly, contributing to functional disability and dependence, as well as working as an important frailty marker. Considering that prevention and rehabilitation of balance decline in elderly individuals requires the development of appropriate clinical and research protocols for measuring balance functions, the aim of the present study was to analyze and compare the efficacy of three fall risk assessment measures - Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and Dynamic Gait Index (DGI)-, in seven healthy elderly individuals. Our results showed that all scales are easily applicable and understandable and do not require raters' training. However, as they assess distinct aspects, only the DGI was able to identify increased fall risk in 4 individuals of the evaluated population

Síndrome do manguito rotador: reabilitação

Iniciamos a elaboraçao desta diretriz com a capacitaçao dos autores por meio da metodologia empregada pelo Oxford Centre for Evidence Based Medicine, para elaboraçao de diretrizes clínicas pelo Programa Diretrizes da Associaçao Médica Brasileira (AMB). Foram revisados artigos nas bases de dados do MedLine (PubMed) e outras fontes de pesquisa, sem limite de tempo. A estratégia de busca utilizada baseou-se em perguntas estruturadas na forma P.I.C.O. (das iniciais "Paciente", "Intervençao", "Controle", "Outcome").We began the preparation of this guideline with the training of the authors using the methodology employed by the Oxford Centre for Evidence-Based Medicine, for the development of clinical guidelines for the Programa Diretrizes da Associaçao Médica Brasileira-AMB (Brazilian Medical Association's Guideline Program-BMA). Articles were reviewed from the MEDLINE (PubMed) database and other research sources, on an open-ended basis. The search strategy used was based on structured questions in the P.I.C.O. form (from the initials of "Patient", "Intervention", "Control", and "Outcome")

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Proposal of an ethics-based framework for prioritization of scarce resources during an influenza pandemic

The goal of pandemic influenza planning is to minimize health and economic losses in the event of a future pandemic. One of the numerous challenges associated with this goal is the need to ration limited medical supplies such as vaccines and antivirals. This thesis seeks to formulate an ethical framework for priority access to these resources. Prioritization strategies must be consistent with the goal of pandemic planning and should reflect societal norms for equitable distribution. According to an ethics framework based on the principles of utility and equity, three groups were granted highest priority for influenza vaccine, namely health care workers, emergency service workers, and high-risk individuals predisposed to severe outcomes following influenza infection. In the case of antivirals, the expectation is that there will be competition between treatment and prophylaxis uses of these drugs. The resulting dilemma---providing primary access to the critically ill in respect of the medical profession's duty of care or prioritizing prophylaxis of health care workers in respect of their right to protection---is the major question which the framework presented in this thesis seeks to resolve

Assessing the Plutonium isotopes and Minor Actinides distribution in PWRs Mixed Oxide nuclear fuel by means of the TRANSURANUS code

The present work concerns the study of Plutonium and some Minor Actinides (MAs) radial distribution in PWRs MOX fuel pellets by means of TRANSURANUS code. The distribution models are obtained by improving the TRANSURANUS burnup model TUBRNP (TRANSURANUS burnup equations), by means of new equations integrated in the program structure. The input files taken as a reference are obtained from the literature analysis carried out in the first step of the work. The first part of the thesis is dedicated to a brief state of the art revision focused on the plutonium issue, the MOX fuel question, and gives also a panoramic EPR-UK and Westinghouse PDR reactors, in order to obtain a framework of the worldwide situation and to gather data for the computational phase. In the second step, the computational one, are described the procedures used to improve the TUBRNP and the results obtained by its application to 6 cases, namely a high burnup fuel, the EPR-UK reference MOX fuel, two weapons-grade MOX fuels and a MOX-EU fuel. Particularly, the analyses have provided the radial distribution of plutonium and MAs in the 6 fuel types. These distributions are analysed in detail and compared with the previous results arising from the old version of TUBRNP, already validated from ITU, in order to find out the principal equations terms that can affect the forecasting and that can be further improved to better describe the phenomenology. Finally, in the third phase, is conducted a brief analysis of the question regarding the radiotoxicity reduction of spent nuclear fuel, quoting the recycling option, and a study of the GHGs emission related to the nuclear fuel cycle, delineating a forecast of future energy scenarios

El impacto de los Identificadores Persistentes (PIDs) en el Repositorio de Datos Académicos RDA-UNR

Se presenta la implementación de Identificadores Persistentes (PIDs) en el Repositorio de Datos Académicos RDA-UNR (https://dataverse.unr.edu.ar). Los problemas detectados fueron la necesidad de identificación única de los conjuntos de datos, de los archivos, de los investigadores y de la Universidad para asegurar la correcta atribución de autoría y facilitar la referenciación precisa de los elementos, además de asegurar la integridad y recuperación de los datos, su correcta citación y vinculación con otros recursos académicos. Se examinan específicamente los identificadores ORCID, DOI y ROR, y se evalúa su presencia y utilización en los metadatos de los conjuntos de datos.Ibero-American Science and Technology Education Consortiu

Implementación de Identificadores Persistentes (PIDs) para aumentar el impacto del Repositorio de Datos Académicos RDA-UNR

Se presenta la implementación de Identificadores Persistentes (PIDs) en el Repositorio de Datos Académicos RDA-UNR (https://dataverse.unr.edu.ar). Los problemas detectados fueron la necesidad de identificación única de los conjuntos de datos, de los archivos, de los investigadores y de la Universidad para asegurar la correcta atribución de autoría y facilitar la referenciación precisa de los elementos, además de asegurar la integridad y recuperación de los datos, su correcta citación y vinculación con otros recursos académicos. Se examinan específicamente los identificadores ORCID, DOI y ROR, y se evalúa su presencia y utilización en los metadatos de los conjuntos de datos.Fil: Salazar, Analía. Universidad Nacional de Rosario; Argentina

El impacto de los Identificadores Persistentes (PIDs) en el Repositorio de Datos Académicos RDA-UNR https://dataverse.unr.edu.ar

El poster presentado aborda la implementación de Identificadores Persistentes (PIDs) en el Repositorio de Datos Académicos RDA-UNR (dataverse.unr.edu.ar). Los problemas detectados fueron la necesidad de identificación única de los conjuntos de datos y archivos, de los investigadores y de la Universidad para asegurar la correcta atribución de autoría y facilitar la referenciación precisa de los elementos, además de asegurar la integridad y recuperación de los datos, su correcta citación y vinculación con otros recursos académicos.Fil: Salazar, Analía. Universidad Nacional de Rosario; Argentin