Extracellular vesicle transfer of lncRNA H19 splice variants to cardiac cells.

The delivery of therapeutic long non-coding RNAs (lncRNA) to the heart by extracellular vesicles (EVs) is promising for heart repair. H19, a lncRNA acting as a major regulator of gene expression within the cardiovascular system, is alternatively spliced, but the loading of its different splice variants into EVs and their subsequent uptake by recipient cardiac cells remain elusive. Here, we dissected the cellular expression of H19 splice variants and their loading into EVs secreted by Wharton-Jelly mesenchymal stromal/stem cells (WJ-MSCs). We demonstrated that overexpression of the mouse H19 gene in WJ-MSCs induces the expression of H19 splice variants at different levels. Interestingly, EVs isolated from the H19-transfected WJ-MSCs (EV-H19) showed similar expression levels for all tested splice variant sets. In vitro, we further demonstrated that EV-H19 was taken up by cardiomyocytes, fibroblasts, and endothelial cells (ECs). Finally, analysis of EV tropism in living rat myocardial slices indicated that EVs were internalized mostly by cardiomyocytes and ECs. Collectively, our results indicated that EVs can be loaded with different lncRNA splice variants and successfully internalized by cardiac cells.

Interpersonal violence against people with intellectual disabilities in São Paulo, Brazil: characteristics of victims, perpetrators and referrals.

INTRODUCTION: Interpersonal violence is a phenomenon that can occur with different people and conditions. However, people with intellectual disabilities have increased vulnerability to this problem, with potential risks to their health and well-being. The aim of this study was to identify the sociodemographic characteristics of people with disabilities who have been victims of interpersonal violence, the profile of the perpetrators and the measures taken after the victims have been cared for. METHODS: This is an exploratory, descriptive, cross-sectional study using the Interpersonal Violence Notification Forms entered into the Brazilian Ministry of Health's Notifiable Diseases Information System. The city of São Paulo was chosen as the setting because it is the largest city in Latin America and has a faster data processing system than other cities. The period covered notifications made between 2016 and 2022. The information was collected between October and November 2023 and a univariate statistical analysis was carried out. Fisher's exact test was used, with a significance level of 5% (α = 0.05). RESULTS: There were 4,603 notifications against people with intellectual disabilities in the period. The forms of physical violence, neglect/abandonment and psychological/moral violence were more frequent in the 15-19 age group, while sexual violence was more frequent in the 10-14 age group (p < 0.001). The sex most often attacked was female in all the forms investigated (p < 0.001) and the skin colors of the most victimized people were black and/or brown, except in cases of neglect/abandonment (p = 0.058). Most of the victims had little schooling (p = 0.012). The aggressions were committed by one person (p < 0.001), known or related to the victim, such as mother or father, except in cases of sexual violence, where strangers were the main perpetrators (p < 0.001). The sex of the perpetrator was male, except in cases of neglect and/or abandonment (p < 0.001), and the age was between 25 and 29 (p = 0.004). In cases of sexual violence, rape was the most frequent and the procedures carried out were blood collection followed by prophylaxis for Sexually Transmitted Infections (STIs) were the main procedures carried out by health professionals (p = 0.004). The majority of referrals made after receiving care were to the health and social assistance network, with few referrals to bodies such as the human rights reference center, guardianship council and police stations (p < 0.001). CONCLUSION: People with intellectual disabilities are highly vulnerable to the forms of violence studied, especially children and adolescents, black or brown, with low levels of education. The perpetrators are usually close people, male and older than the victims. The referrals made by health professionals did not prioritize the victim's safety and the guarantee of human rights. Lines of care for the health of victims of violence should be implemented, taking into account special aspects, such as people with intellectual disabilities, whose search for help can be difficult.

Changes in Oxidised Phospholipids in Response to Oxidative Stress in Microtubule-Associated Protein Tau (MAPT) Mutant Dopamine Neurons.

Microtubule-associated protein Tau (MAPT) is strongly associated with the development of neurodegenerative diseases. In addition to driving the formation of neurofibrillary tangles (NFT), mutations in the MAPT gene can also cause oxidative stress through hyperpolarisation of the mitochondria. This study explores the impact that MAPT mutation is having on phospholipid metabolism in iPSC-derived dopamine neurons, and to determine if these effects are exacerbated by mitochondrial and endoplasmic reticulum stress. Neurons that possessed a mutated copy of MAPT were shown to have significantly higher levels of oxo-phospholipids (Oxo-PL) than wild-type neurons. Oxidation of the hydrophobic fatty acid side chains changes the chemistry of the phospholipid leading to disruption of membrane function and potential cell lysis. In wild-type neurons, both mitochondrial and endoplasmic reticulum stress increased Oxo-PL abundance; however, in MAPT mutant neurons mitochondrial stress appeared to have a minimal effect. Endoplasmic reticulum stress, surprisingly, reduced the abundance of Oxo-PL in MAPT mutant dopamine neurons, and we postulate that this reduction could be modulated through hyperactivation of the unfolded protein response and X-box binding protein 1. Overall, the results of this study contribute to furthering our understanding of the regulation and impact of oxidative stress in Parkinson's disease pathology.

Primary Health Care and Tuberculosis Detection during the COVID-19 Pandemic: Crucial Actions for Intensifying Efforts.

BACKGROUND: Tuberculosis has been considered a global emergency since 1993, and controlling it has become even more challenging since 2020 due to the health and social crisis resulting from the COVID-19 pandemic. This study aimed to identify the impact of the COVID-19 pandemic on tuberculosis case detection activities within primary health Care in the largest city in Brazil. METHODS: This is a cross-sectional and analytical study on the provision of tuberculosis detection actions in primary healthcare units during the pandemic period. A descriptive analysis was performed for characterization, and Generalized Mixed Models were used for evaluating associations, with a Bonferroni post hoc test applied. RESULTS: The study sample comprised 80 health units in the municipality. There was a moderate alteration level in the provision of consultations for individuals with signs and symptoms of tuberculosis in 2020 (13.8%) and in 2021 (15.1%). Statistical significance (p < 0.05) was found between the pandemic period and detection actions, with a lower alteration level in 2022. CONCLUSIONS: Tuberculosis detection activities underwent changes due to the COVID-19 pandemic, mainly in 2020, which was associated with alterations in consultation and case notification provision.

Variant-specific effects of GBA1 mutations on dopaminergic neuron proteostasis.

Glucocerebrosidase 1 (GBA1) mutations are the most important genetic risk factors for Parkinson's disease (PD). Clinically, mild (e.g., p.N370S) and severe (e.g., p.L444P and p.D409H) GBA1 mutations have different PD phenotypes, with differences in age at disease onset, progression, and the severity of motor and non-motor symptoms. We hypothesize that GBA1 mutations cause the accumulation of α-synuclein by affecting the cross-talk between cellular protein degradation mechanisms, leading to neurodegeneration. Accordingly, we tested whether mild and severe GBA1 mutations differentially affect the degradation of α-synuclein via the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and macroautophagy and differentially cause accumulation and/or release of α-synuclein. Our results demonstrate that endoplasmic reticulum (ER) stress and total ubiquitination rates were significantly increased in cells with severe GBA1 mutations. CMA was found to be defective in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons with mild GBA1 mutations, but not in those with severe GBA1 mutations. When examining macroautophagy, we observed reduced formation of autophagosomes in cells with the N370S and D409H GBA1 mutations and impairments in autophagosome-lysosome fusion in cells with the L444P GBA1 mutation. Accordingly, severe GBA1 mutations were found to trigger the accumulation and release of oligomeric α-synuclein in iPSC-derived dopaminergic neurons, primarily as a result of increased ER stress and defective macroautophagy, while mild GBA1 mutations affected CMA, which is mainly responsible for the degradation of the monomeric form of α-synuclein. Overall, our findings provide new insight into the molecular basis of the clinical variability in PD associated with different GBA1 mutations.

Non-violent communication as a technology in interpersonal relationships in health work: a scoping review.

BACKGROUND: Working in healthcare environments is highly stressful for most professionals and can trigger problems in interpersonal relationships that can result in horizontal violence. In order to prevent violence and improve the working environment, some strategies can be implemented to provide well-being for all those involved, whether directly or indirectly in health care, such as non-violent communication. The aim of this study was to map and synthesize the available scientific evidence on the use of Nonviolent Communication as a technology for a culture of peace in interpersonal relationships in healthcare. METHODS: This is a scoping review carried out in the National Library of Medicine (PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Excerpa Medica DataBASE (Embase), PsycINFO - APA/ PsycNET (American Psychological Association) and Latin American and Caribbean Health Sciences Literature (LILACS) databases between March and August 2023. The eligibility criteria used were studies that addressed the topic of NVC in the area of health, published in Portuguese, Spanish or English, with no time restrictions. RESULTS: 53 studies were found in the databases. Two additional studies were extracted from of primary research. In the first exclusion phase, 16 texts were removed due to being duplicated. 39 articles were potentially relevant, and full-texts were reviewed for eligibility along with the inclusion and exclusion criteria Thus, seven studies were included in this review, published in English (five) and Portuguese (two), two of which were carried out in Brazil, one in the United States of America, one in South Korea, one in France, one in Canada and one in Thailand. In terms of the type of study/publication, two studies were reflections, one was a review, one was a mixed study, one was an experience report and two were experimental. The studies were predominantly of high and moderate methodological quality (85.7%). The total number of participants in the studies was 185. The studies showed that NVC is a technology that has made it possible to improve interpersonal relationships between health professionals. Training programs or educational intervention projects on the subject are useful for familiarizing professionals with the subject and demonstrating situations in which the technique can be included. CONCLUSION: The global scientific literature indicates that Nonviolent Communication is a significant resource for improving interpersonal relationships in healthcare work. This approach can be adopted as a strategy by managers and decision-makers, both to resolve conflicts and to prevent aggressive situations between health professionals, especially when it comes to moral or psychological aspects.

Nursing rights in comics: educational technological innovation report.

OBJECTIVES: to report an educational technology construction on nursing professionals' rights. METHODS: an experience report on educational technology construction during the crediting of university extension hours in an undergraduate nursing course at a Brazilian public university, between March and June 2023. The Deming cycle was used as a procedural method. RESULTS: four meetings were held between students and extension workers. Eight comic books were produced based on the Code of Ethics for Nurses, addressing professional autonomy, fair remuneration, risk-free work, denial of exposure in the media and others. The Deming cycle proved to be an important strategy for constructing products. CONCLUSIONS: nursing professionals' rights must be discussed and improved. Educational technologies, such as comic books, provide playful and reflective learning.

POSEIDON: Peptidic Objects SEquence-based Interaction with cellular DOmaiNs: a new database and predictor.

Cell-penetrating peptides (CPPs) are short chains of amino acids that have shown remarkable potential to cross the cell membrane and deliver coupled therapeutic cargoes into cells. Designing and testing different CPPs to target specific cells or tissues is crucial to ensure high delivery efficiency and reduced toxicity. However, in vivo/in vitro testing of various CPPs can be both time-consuming and costly, which has led to interest in computational methodologies, such as Machine Learning (ML) approaches, as faster and cheaper methods for CPP design and uptake prediction. However, most ML models developed to date focus on classification rather than regression techniques, because of the lack of informative quantitative uptake values. To address these challenges, we developed POSEIDON, an open-access and up-to-date curated database that provides experimental quantitative uptake values for over 2,300 entries and physicochemical properties of 1,315 peptides. POSEIDON also offers physicochemical properties, such as cell line, cargo, and sequence, among others. By leveraging this database along with cell line genomic features, we processed a dataset of over 1,200 entries to develop an ML regression CPP uptake predictor. Our results demonstrated that POSEIDON accurately predicted peptide cell line uptake, achieving a Pearson correlation of 0.87, Spearman correlation of 0.88, and r2 score of 0.76, on an independent test set. With its comprehensive and novel dataset, along with its potent predictive capabilities, the POSEIDON database and its associated ML predictor signify a significant leap forward in CPP research and development. The POSEIDON database and ML Predictor are available for free and with a user-friendly interface at https://moreiralab.com/resources/poseidon/ , making them valuable resources for advancing research on CPP-related topics. Scientific Contribution Statement: Our research addresses the critical need for more efficient and cost-effective methodologies in Cell-Penetrating Peptide (CPP) research. We introduced POSEIDON, a comprehensive and freely accessible database that delivers quantitative uptake values for over 2,300 entries, along with detailed physicochemical profiles for 1,315 peptides. Recognizing the limitations of current Machine Learning (ML) models for CPP design, our work leveraged the rich dataset provided by POSEIDON to develop a highly accurate ML regression model for predicting CPP uptake.

Violência contra mulher parda e preta durante a pandemia: revisão de escopo / Violencia contra mujeres pardas y negras durante la pandemia: revisión de alcance / Violence against brown and black women during the pandemic: a scoping review

Resumo Objetivo Mapear e sumarizar as principais evidências disponíveis sobre a violência por parceiro íntimo contra a mulher parda e preta durante a pandemia COVID-19. Métodos Trata-se de uma revisão de escopo nas bases de dados National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Excerpa Medica DataBASE, PsycINFO - APA PsycNET e Literatura Latino-Americana e do Caribe em Ciências da Saúde. Os critérios de inclusão foram estudos sobre violência interpessoal contra a mulher parda e preta após o decreto de pandemia COVID-19, perpetrada por parceiro íntimo, publicados a partir de 2020, nos idiomas português, espanhol ou inglês. Excluíram-se editoriais, cartas resposta, retratações e estudos voltados à violência autoprovocada. Foi realizada análise descritiva. Resultados Foram obtidos 26 estudos e após a seleção obteve-se a amostra de oito artigos, publicados entre 2020 e 2022. Os resultados evidenciaram estudos majoritariamente norte-americanos, contudo apontaram para a violência por parceiro íntimo contra a mulher parda e preta como um fenômeno global durante a pandemia. As vítimas apresentavam múltiplas condições de vulnerabilidade e encontraram várias barreiras de acesso aos serviços de saúde e segurança pública, incluindo o racismo. Medidas de prevenção e controle foram escassas e geraram consequências à saúde integral da mulher. Conclusão O fenômeno foi caracterizado como um agravo global durante a pandemia COVID-19. Estratégias de enfrentamento individuais, coletivas e políticas foram criadas pelas vítimas. Políticas públicas de prevenção e controle da violência por parceiro íntimo não foram adequadamente aplicadas em muitos países durante a pandemia.

Resumen Objetivo Mapear y resumir las principales evidencias disponibles sobre la violencia contra mujeres pardas y negras por parte de la pareja íntima durante la pandemia de COVID-19. Métodos Se trata de una revisión de alcance en las bases de datos National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Excerpa Medica DataBASE, PsycINFO - APA PsycNET y Literatura Latinoamericana y del Caribe en Ciencias de la Salud. Los criterios de inclusión fueron estudios sobre violencia interpersonal contra mujeres pardas y negras después del decreto de pandemia de COVID-19, ejercida por su pareja íntima, publicados a partir de 2020, en idioma portugués, español o inglés. Se excluyeron editoriales, cartas de respuesta, retractaciones y estudios sobre violencia autoprovocada. Se realizó análisis descriptivo. Resultados Se obtuvieron 26 estudios y, después de la selección, se obtuvo una muestra de ocho artículos, publicados entre 2020 y 2022. Los resultados evidenciaron estudios mayormente norteamericanos, pero señalaron que la violencia contra mujeres pardas y negras por parte de su pareja íntima fue un fenómeno global durante la pandemia. Las víctimas presentaron múltiples condiciones de vulnerabilidad y encontraron varias barreras de acceso a los servicios de salud y seguridad pública, inclusive racismo. Las medidas de prevención y control fueron escasas y generaron consecuencias en la salud integral de las mujeres. Conclusión El fenómeno fue caracterizado como un agravio global durante la pandemia de COVID-19. Las estrategias de enfrentamiento individuales, colectivas y políticas fueron creadas por las víctimas. Las políticas públicas de prevención y control de la violencia por parte de pareja íntima no fueron aplicadas adecuadamente en muchos países durante la pandemia. Open Science Framework: https://osf.io/bdsf7/

Abstract Objective To map and summarize the main available evidence on intimate partner violence against brown and black women during the COVID-19 pandemic. Methods This is a scoping review carried out in the National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Excerpa Medica DataBASE, PsycINFO - APA PsycNET and Latin American and Caribbean Literature in Health Sciences databases. Studies on interpersonal violence against brown and black women after the COVID-19 pandemic decree, perpetrated by an intimate partner, published from 2020 onwards in Portuguese, Spanish or English, were included. Editorials, response letters, retractions and studies focused on self-inflicted violence were excluded. Descriptive analysis was carried out. Results A total of 26 studies were obtained, and after selection, a sample of eight articles was obtained, published between 2020 and 2022. The results showed mostly North American studies, however, they pointed to intimate partner violence against brown and black women as a global phenomenon during the pandemic. The victims presented multiple conditions of vulnerability and encountered several barriers to accessing health and public safety services, including racism. Prevention and control measures were scarce and had consequences for women's overall health. Conclusion The phenomenon was characterized as a global problem during the COVID-19 pandemic. Individual, collective and political coping strategies were created by the victims. Public policies to prevent and control intimate partner violence were not adequately implemented in many countries during the pandemic. Open Science Framework: https://osf.io/bdsf7/

Nursing rights in comics: educational technological innovation report / Los derechos de enfermería en el cómic: informe de innovación tecnológica educativa / Direitos da enfermagem em quadrinhos: relato de inovação tecnológica educacional

ABSTRACT Objectives: to report an educational technology construction on nursing professionals' rights. Methods: an experience report on educational technology construction during the crediting of university extension hours in an undergraduate nursing course at a Brazilian public university, between March and June 2023. The Deming cycle was used as a procedural method. Results: four meetings were held between students and extension workers. Eight comic books were produced based on the Code of Ethics for Nurses, addressing professional autonomy, fair remuneration, risk-free work, denial of exposure in the media and others. The Deming cycle proved to be an important strategy for constructing products. Conclusions: nursing professionals' rights must be discussed and improved. Educational technologies, such as comic books, provide playful and reflective learning.

RESUMEN Objetivos: informar la construcción de una tecnología educativa sobre los derechos de los profesionales de enfermería. Métodos: relato de experiencia sobre la construcción de tecnología educativa durante la acreditación de horas de extensión universitaria en una carrera de pregrado en enfermería en una universidad pública brasileña, entre marzo y junio de 2023. Se utilizó el ciclo de Deming como método procesal. Resultados: se realizaron cuatro reuniones entre estudiantes y extensionistas. Se produjeron ocho historietas basadas en el Código de Ética para los Profesionales de Enfermería, abordando la autonomía profesional, la remuneración justa, el trabajo libre de riesgos, la negación de la exposición en los medios de comunicación y otros. El ciclo de Deming demostró ser una estrategia importante para la construcción de productos. Conclusiones: los derechos de los profesionales de enfermería deben ser discutidos y mejorados. Las tecnologías educativas, como los cómics, proporcionan un aprendizaje lúdico y reflexivo.

RESUMO Objetivos: relatar a construção de uma tecnologia educacional sobre os direitos dos profissionais de enfermagem. Métodos: relato de experiência sobre a construção de tecnologia educacional durante a creditação de horas de extensão universitária em uma disciplina da graduação em enfermagem de uma universidade pública brasileira, entre março e junho de 2023. Utilizou-se o ciclo de Deming como método processual. Resultados: foram realizados quatro encontros entre estudantes e extensionistas. Oito histórias em quadrinhos foram produzidas pautadas no Código de Ética dos Profissionais de Enfermagem abordando autonomia profissional, remuneração justa, trabalho sem riscos, negação à exposição em mídias e outros. O ciclo de Deming mostrou-se importante estratégia para construção dos produtos. Conclusões: os direitos dos profissionais de enfermagem devem ser discutidos e aprimorados. Tecnologias educacionais, como histórias em quadrinhos, proporcionam aprendizagem lúdica e reflexiva.

Profile and characteristics of violence against older adults during the COVID-19 pandemic / Perfil e características da violência contra a pessoa idosa durante a pandemia COVID-19 / Perfil y características de la violencia contra los adultos mayores durante la pandemia de COVID-19

Abstract Objective: to identify the sociodemographic profile and the characteristics of interpersonal violence against older adults during the first year of the COVID-19 pandemic in a capital city from the Brazilian Southeast region. Method: a descriptive and exploratory research study with a cross-sectional design based on the notifications of suspected or confirmed cases of violence against older adults between March 2020 and March 2021. A univariate statistical analysis and Fisher's exact test (p<0.05) were performed. Results: a total of 2,681 notifications were recorded during the period. The main victims were individuals aged between 60 and 64 years old, female, white-skinned and with low schooling levels. The instances of violence were more frequent in the victims' homes. Physical and psychological violence predominated, through physical force/beatings and threats, respectively. Most of the aggressors were male, younger than the victims and generally their children or intimate partners. The aggressions were perpetrated more than once and were driven by generational conflicts. There was low referral to entities for the protection of older adults. Conclusion: the sociodemographic profile found evidences vulnerable victims, subjected to many types of violence, and at a potential risk against their overall health.

Resumo Objetivo: identificar o perfil sociodemográfico e as características da violência interpessoal contra a pessoa idosa no primeiro ano da pandemia COVID-19 em uma capital da região sudeste do Brasil. Método: pesquisa descritiva, exploratória, com delineamento transversal a partir da análise das notificações de casos suspeitos ou confirmados de violência contra a pessoa idosa, ocorridas entre março de 2020 e março de 2021. Foi realizada a análise estatística univariada e teste exato de Fisher (p<0,05). Resultados: houve 2681 notificações no período. As principais vítimas foram pessoas com idade entre 60 e 64 anos, do sexo feminino, brancas e com baixa escolaridade. As ocorrências tiveram maior frequência nos domicílios. As violências físicas e psicológicas foram as mais comuns, com uso de força física/espancamento e ameaça, respectivamente. O agressor era, em sua maioria, do sexo masculino, mais jovem do que a vítima, geralmente filho ou parceiro íntimo. As agressões ocorreram mais de uma vez e foram motivadas por conflitos geracionais. Houve baixo encaminhamento para órgãos de proteção a pessoa idosa. Conclusão: o perfil sociodemográfico encontrado evidencia vítimas vulneráveis, sujeitas a muitas formas de violência e com potenciais riscos à integralidade de sua saúde.

Resumen Objetivo: identificar el perfil sociodemográfico y las características de la violencia interpersonal contra los adultos mayores en el primer año de la pandemia de COVID-19 en una ciudad capital de la región sureste de Brasil. Método: investigación descriptiva, exploratoria con diseño transversal a partir del análisis de las notificaciones de casos sospechosos o confirmados de violencia contra el adulto mayor, ocurridos entre marzo de 2020 y marzo de 2021. Se realizó un análisis estadístico univariado y la prueba exacta de Fisher (p< 0,05). Resultados: hubo 2681 notificaciones en el período. Las principales víctimas fueron personas entre 60 y 64 años, de sexo femenino, blancas y con baja escolaridad. La mayoría de los casos se registró en el hogar. La violencia física y psicológica fueron las más comunes, con uso de fuerza física/golpes y amenaza, respectivamente. El agresor era generalmente del sexo masculino, más joven que la víctima, hijo o pareja. Las agresiones se produjeron más de una vez y fueron motivadas por conflictos generacionales. Hubo baja derivación a organismos de protección de adultos mayores. Conclusión: el perfil sociodemográfico obtenido revela que son víctimas vulnerables, sujetas a múltiples formas de violencia y que la integridad de su salud está en riesgo potencial.

Health care for people with tuberculosis/HIV co-infection from the multidisciplinary team's perspective.

OBJECTIVE: to know the multidisciplinary team's perspective about the health care of people with tuberculosis and human immunodeficiency virus co-infection in relation to treatment. METHODS: this is a descriptive-exploratory study, with a qualitative approach, carried out in a health care service in São Paulo, from May to June 2019. Semi-structured interviews were conducted with nine professionals from the multidisciplinary team. Data were processed through discourse analysis with the support of webQDA. RESULTS: Two empirical categories emerged: Health care interfaces for people with tuberculosis and human immunodeficiency virus co-infection; Barriers and facilitators for health care for people with co-infection. FINAL CONSIDERATIONS: the health-disease process in co-infection is mediated by conditions that positively or negatively interfere with treatment compliance. People's health care goes beyond exclusively clinical assistance and requires the recognition of needs in a broad perspective.

Trends in trust of professional groups in Portugal during COVID-19.

We repeated a Portuguese study, 5 months after a first evaluation, to observe any change in the average levels of trust of professional groups during the COVID-19 pandemic. From our sample of the Portuguese population, 1455 completed the questionnaire from June through September 2020, and 1156 during 2 months, February and March 2021. We found a trend toward higher trust of medical doctors, nurses, and researchers. Analysis of changes between the two pandemic periods (first and second lockdown) showed a statistically significant increase in trust in nurses (t = - 2.01; p = 0.04) and researchers (t = - 2.40; p = 0.02), and the opposite trend for journalists and politicians. This study shows a trend in increasing trust of the Portuguese people toward science-based activities during the COVID-19 pandemic.

Construction of educational technology on non-violent communication between health professionals: an experience report.

OBJECTIVE: to report the construction of an educational technology to promote non-violent communication for health professionals. METHODS: an experience report on the development of an educational technology on non-violent communication for health professionals, prepared by members of a social university extension project. The Plan-Do-Study-Act cycle was used as a process or product management procedure. RESULTS: two complete management method cycles were performed. A mini almanac was generated as a final product, which addressed the main elements of non-violent communication, an example of its use in everyday life, hobbies and interspersed activities. CONCLUSION: educational technology construction (mini almanac) by members of a university extension project was facilitated using the Plan-Do-Study-Act cycle, proving to be a resource for disseminating non-violent communication in health work and promoting a culture of peace.

Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson's disease GBA-N370S dopamine neurons.

Variants at the GBA locus, encoding glucocerebrosidase, are the strongest common genetic risk factor for Parkinson's disease (PD). To understand GBA-related disease mechanisms, we use a multi-part-enrichment proteomics and post-translational modification (PTM) workflow, identifying large numbers of dysregulated proteins and PTMs in heterozygous GBA-N370S PD patient induced pluripotent stem cell (iPSC) dopamine neurons. Alterations in glycosylation status show disturbances in the autophagy-lysosomal pathway, which concur with upstream perturbations in mammalian target of rapamycin (mTOR) activation in GBA-PD neurons. Several native and modified proteins encoded by PD-associated genes are dysregulated in GBA-PD neurons. Integrated pathway analysis reveals impaired neuritogenesis in GBA-PD neurons and identify tau as a key pathway mediator. Functional assays confirm neurite outgrowth deficits and identify impaired mitochondrial movement in GBA-PD neurons. Furthermore, pharmacological rescue of glucocerebrosidase activity in GBA-PD neurons improves the neurite outgrowth deficit. Overall, this study demonstrates the potential of PTMomics to elucidate neurodegeneration-associated pathways and potential drug targets in complex disease models.

CRISPR-Cas9 genetic screen leads to the discovery of L-Moses, a KAT2B inhibitor that attenuates Tunicamycin-mediated neuronal cell death.

Accumulation of aggregated and misfolded proteins, leading to endoplasmic reticulum stress and activation of the unfolded protein response, is a hallmark of several neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Genetic screens are powerful tools that are proving invaluable in identifying novel modulators of disease associated processes. Here, we performed a loss-of-function genetic screen using a human druggable genome library, followed by an arrayed-screen validation, in human iPSC-derived cortical neurons. We identified and genetically validated 13 genes, whose knockout was neuroprotective against Tunicamycin, a glycoprotein synthesis inhibitor widely used to induce endoplasmic reticulum stress. We also demonstrated that pharmacological inhibition of KAT2B, a lysine acetyltransferase identified by our genetic screens, by L-Moses, attenuates Tunicamycin-mediated neuronal cell death and activation of CHOP, a key pro-apoptotic member of the unfolded protein response in both cortical and dopaminergic neurons. Follow-up transcriptional analysis suggested that L-Moses provided neuroprotection by partly reversing the transcriptional changes caused by Tunicamycin. Finally, L-Moses treatment attenuated total protein levels affected by Tunicamycin, without affecting their acetylation profile. In summary, using an unbiased approach, we identified KAT2B and its inhibitor, L-Moses, as potential therapeutic targets for neurodegenerative diseases.

Fatores relacionados à sobrecarga e ao autocuidado para hipertensão em cuidadores familiares / Factors related to burden and self-care for hypertension in family caregivers / Factores relacionados con la carga y el autocuidado de la hipertensión en cuidadores familiares

RESUMO Objetivo: identificar os fatores relacionados à sobrecarga e ao autocuidado para hipertensão em cuidadores familiares. Método: pesquisa online e transversal, com 68 cuidadores familiares de pessoas idosas, realizada entre dezembro de 2021 e fevereiro de 2022, no Brasil. Foram aplicados questionários sobre atividade de cuidador, Questionário de Avaliação da Sobrecarga do Cuidador Informal e Escala Autocuidado de Hipertensão. Foram realizadas análises descritivas e analíticas. Resultados: cuidadores que residiam com idoso (p=0,0006) e sem dia de descanso (p=0,0097) apresentaram maior sobrecarga. Quanto maior o tempo como cuidador (p=0,0411), menor o escore do domínio medidas de manejo do autocuidado durante a descompensação pressórica. Cuidadores que recebiam auxílio de outra pessoa (p=0,0379) apresentaram maior escore no domínio grau de confiança do paciente para o autocuidado relacionado à hipertensão. Conclusão: este estudo contribui para maior compreensão das variáveis referentes à atividade de cuidador relacionada à sobrecarga e ao autocuidado para hipertensão de cuidadores de pessoas idosas.

ABSTRACT Objective: To identify factors related to burden and self-care for hypertension in family caregivers. Method: an online, cross-sectional survey of 68 family caregivers of elderly people, carried out between December 2021 and February 2022 in Brazil. Questionnaires on caregiver activity, the Informal Caregiver Burden Assessment Questionnaire and the Hypertension Self-Care Scale were applied. Descriptive and analytical analyses were carried out. Results: caregivers who lived with the elderly (p=0.0006) and had no rest day (p=0.0097) showed greater burden. The longer the time as a caregiver (p=0.0411), the lower the score in the domain of self-care management measures during blood pressure decompensation. Caregivers who received help from someone else (p=0.0379) had a higher score in the domain of the patient's degree of confidence in self-care related to hypertension. Conclusion: This study contributes to a better understanding of the variables relating to caregiver activity related to burden and self-care for hypertension among caregivers of elderly people.

RESUMEN Objetivo: identificar los factores relacionados con la carga y el autocuidado de la hipertensión en cuidadores familiares. Material y método: encuesta transversal online a 68 cuidadores familiares de ancianos, realizada entre diciembre de 2021 y febrero de 2022 en Brasil. Se aplicaron cuestionarios sobre la actividad del cuidador, el Cuestionario de Evaluación de la Carga del Cuidador Informal y la Escala de Autocuidado de la Hipertensión. Se realizaron análisis descriptivos y analíticos. Resultados: los cuidadores que vivían con el anciano (p=0,0006) y no tenían día de descanso (p=0,0097) mostraron mayor carga. Cuanto mayor era el tiempo como cuidador (p=0,0411), menor era la puntuación en el dominio de las medidas de gestión del autocuidado durante la descompensación por presión. Los cuidadores que recibían ayuda de otra persona (p=0,0379) tenían una puntuación más alta en el dominio del grado de confianza del paciente en el autocuidado relacionado con la hipertensión. Conclusión: Este estudio contribuye a una mayor comprensión de las variables relativas a la actividad del cuidador relacionadas con la carga y el autocuidado de la hipertensión de los cuidadores de personas mayores.

TRAP1 Is Expressed in Human Retinal Pigment Epithelial Cells and Is Required to Maintain their Energetic Status.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss and blindness in elderly people worldwide. The damage to the retinal pigment epithelium (RPE) triggered by oxidative stress plays a central role in the onset and progression of AMD and results from the excessive accumulation of reactive oxygen species (ROS) produced mainly by mitochondria. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecular chaperone that contributes to the maintenance of mitochondrial integrity by decreasing the production and accumulation of ROS. The present study aimed to evaluate the presence and the role of TRAP1 in the RPE. Here, we report that TRAP1 is expressed in human adult retinal pigment epithelial cells and is located mainly in the mitochondria. Exposure of RPE cells to hydrogen peroxide decreases the levels of TRAP1. Furthermore, TRAP1 silencing increases intracellular ROS production and decreases mitochondrial respiratory capacity without affecting cell proliferation. Together, these findings offer novel insights into TRAP1 functions in RPE cells, opening possibilities to develop new treatment options for AMD.

Profile and characteristics of violence against older adults during the COVID-19 pandemic.

OBJECTIVE: to identify the sociodemographic profile and the characteristics of interpersonal violence against older adults during the first year of the COVID-19 pandemic in a capital city from the Brazilian Southeast region. METHOD: a descriptive and exploratory research study with a cross-sectional design based on the notifications of suspected or confirmed cases of violence against older adults between March 2020 and March 2021. A univariate statistical analysis and Fisher's exact test (p<0.05) were performed. RESULTS: a total of 2,681 notifications were recorded during the period. The main victims were individuals aged between 60 and 64 years old, female, white-skinned and with low schooling levels. The instances of violence were more frequent in the victims' homes. Physical and psychological violence predominated, through physical force/beatings and threats, respectively. Most of the aggressors were male, younger than the victims and generally their children or intimate partners. The aggressions were perpetrated more than once and were driven by generational conflicts. There was low referral to entities for the protection of older adults. CONCLUSION: the sociodemographic profile found evidences vulnerable victims, subjected to many types of violence, and at a potential risk against their overall health.