RESUMO
Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.
Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Sintomas Prodrômicos , Substância Negra , Animais , Masculino , Substância Negra/metabolismo , Substância Negra/patologia , Substância Negra/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Doenças Neuroinflamatórias/patologia , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Camundongos , Microglia/metabolismo , Microglia/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ansiedade/etiologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologiaRESUMO
Metal encapsulation delivers a straightforward strategy to improve miscellaneous nanoparticle properties and qualifies the resulting nanocomposite for exceptional application, including bioimaging, drug release, and theranostic development. Besides crucial applications, investigations associated with the nanocomposite impact on the biological media are highly relevant from a pharmacological viewpoint. Such studies can be conducted by exploring nanocomposite attributes and all aspects of their interaction with proteins existing in biofluids. Based on these aspects, the present work examines manganese-encapsulated carbonaceous nanocomposite (MnCQD) and their interaction with plasma proteins. On one side, the obtained nanocomposite has almost spherical shapes (≈12 nm in size), an appropriate composition and interesting optical properties for bioimaging applications. On another side, MnCQD quenches the fluorescence of two plasma proteins (BSA and HTF) following a static mechanism, confirming the formation of the MnCQD-BSA and MnCQD-HTF complexes. Although hydrophobic forces guide the stability of both formed complexes, MnCQD binds preferentially to BSA compared to HTF, with affinity constants differing by almost an order of magnitude. Furthermore, HTF and BSA underwent modifications in their secondary structure provoked due to contact with the nanocomposite, which also presented neglectable opsonization levels when exposed to appropriate biological media. These results highlight the MnCQD outstanding potential to be employed in diverse bioapplications.Communicated by Ramaswamy H. Sarma.
Assuntos
Manganês , Nanocompostos , Opsonização , Fluorescência , Proteínas Sanguíneas , Nanocompostos/química , Soroalbumina Bovina/química , Ligação Proteica , Espectrometria de FluorescênciaRESUMO
BACKGROUND: Metallic nanoparticles (NPs) are widely used as food additives for human consumption. NPs reach the bloodstream given their small size, getting in contact with all body organs and cells. NPs have adverse effects on the respiratory and intestinal tract; however, few studies have focused on the toxic consequences of orally ingested metallic NPs on the cardiovascular system. Here, the effects of two food-grade additives on the cardiovascular system were analyzed. METHODS: Titanium dioxide labeled as E171 and zinc oxide (ZnO) NPs were orally administered to Wistar rats using an esophageal cannula at 10 mg/kg bw every other day for 90 days. We evaluated cardiac cell morphology and death, expression of apoptotic and autophagic proteins in cardiac mitochondria, mitochondrial dysfunction, and concentration of metals on cardiac tissue. RESULTS: Heart histology showed important morphological changes such as presence of cellular infiltrates, collagen deposition and mitochondrial alterations in hearts from rats exposed to E171 and ZnO NPs. Intracellular Cyt-C levels dropped, while TUNEL positive cells increased. No significant changes in the expression of inflammatory cytokines were detected. Both NPs altered mitochondrial function indicating cardiac dysfunction, which was associated with an elevated concentration of calcium. ZnO NPs induced expression of caspases 3 and 9 and two autophagic proteins, LC3B and beclin-1, and had the strongest effect compared to E171. CONCLUSIONS: E171 and ZnO NPs induce adverse cardiovascular effects in rats after 90 days of exposure, thus food intake containing these additives, should be taken into consideration, since they translocate into the bloodstream and cause cardiovascular damage.
Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Ratos , Humanos , Animais , Óxido de Zinco/toxicidade , Ratos Wistar , Nanopartículas/toxicidade , Coração , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Aditivos Alimentares/toxicidadeRESUMO
Epidemiological studies imply there is a higher risk of cardiovascular disease in menopausal women. Some explanations suggest a lack of estrogens as the cause, but estrogens do not disappear completely and are just transformed into different products called estrogenic degradation metabolites (EDMs). When estrogens are metabolized, reactive oxygen species (ROS) increase, causing DNA damage and increasing oxidative stress. These conditions are associated to neurodegenerative diseases and different types of cancer. However, their effect on the cardiovascular system remains unknown. This paper compares estrogenic metabolite levels in serum from post-menopausal women with cardiovascular risk (CAC>1) and with establish cardiovascular disease (CVD), against levels in healthy women (Ctrl). Sample sera were obtained from the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Serum levels of eleven estrogenic metabolites were quantified by High performance liquid chromatography (HPLC) and oxidative stress markers such as ROS, lipoperoxidation levels (TBARS), total antioxidant capacity (TAC), super oxide dismutase activity (SOD) and cytokine levels were evaluated. 8-hydroxy-2-deoxyguanosine (8-OHdG) was also determined as a marker of nuclear damage.There were significant differences between serum levels of some EDMs in CAC> 1 and CVD vs. serum levels in Ctrl women. Results also revealed an increase in oxidative stress and a diminished capacity to manage oxidative stress. These findings provide an overview, and suggest that some estrogenic metabolites may be associated with an increased risk of CVD in menopausal women. However, additional studies are needed to evaluate the impact of these EDMs directly on cardiovascular function.
Assuntos
Doenças Cardiovasculares , Cardiopatias , Feminino , Humanos , Estrogênios/metabolismo , Doenças Cardiovasculares/etiologia , Espécies Reativas de Oxigênio , MenopausaRESUMO
Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex (TSC), and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, permits the formation of tumors that can lead to developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that total Tuberin levels are tightly regulated through developmental stages in the embryonic brain. At a cell biology level, we show that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. This functional data supports the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.
Assuntos
Proteínas Repressoras , Proteínas Supressoras de Tumor , Feminino , Humanos , Gravidez , Encéfalo/metabolismo , Encéfalo/patologia , Diferenciação Celular , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND AND OBJECTIVES: Hospitalization by Covid-19 can cause persistent functional consequences after hospital discharge due to direct and indirect effects of SARS-COV-2 in several organs and systems of the body added to post-intensive care syndrome and prolonged bed rest. These impacts can lead to dependency in activities of daily living, mainly in older people due to aging process and functional decline. This study aimed to compare the effects of hospitalization by Covid-19 on functional capacity of adults and older people and to identify its associated factors. METHODS: Cross-sectional observational study of 159 survivors of hospitalization by Covid-19 after 1 month from discharge at Hospital das Clínicas of the University of São Paulo, divided into groups: adults (aged < 60 years) and older people (aged ≥ 60 years). Those who did not accept to participate, without availability or without ability to understand the questionnaires were excluded. Functional capacity was assessed by the Barthel Index and patients were classified according to their scores. Data analysis was performed in JASP Statistics program and the sample was compared between the age groups. Wilcoxon test was applied to compare before and after periods, Mann-Whitney test was used for between groups comparison. We adopted alpha = 0.05. RESULTS: The total Barthel Index median score was lower 1 month after hospital discharge than in the pre-Covid-19 period. Older people had worse functional status than adults before and also showed greater impairment after hospital discharge. Both groups showed lower Barthel Index classification than before, and older people presented more functional dependence than adults in both periods. Age, sarcopenia and frailty were associated factors. DISCUSSION: Hospitalization by Covid-19 impacts functional capacity after 1 month from discharge, especially in older people. Age, sarcopenia and frailty are associated factors. These results suggest need for care and rehabilitation of Covid-19 survivors.
Assuntos
COVID-19 , Fragilidade , Sarcopenia , Humanos , Adulto , Idoso , Atividades Cotidianas , Estudos Transversais , SARS-CoV-2 , HospitalizaçãoRESUMO
Tuberin is a major component of the protein regulatory complex known as the Tuberous Sclerosis Complex and plays a crucial role in cell cycle progression and protein synthesis. Mutations in the Tuberin gene, TSC2, lead to the formation of benign tumors in many organ systems and causes the Tuberous Sclerosis Complex disorder. Genotypes ranging from point mutations to large deletions in the TSC2 gene have been clinically characterized with a wide range of phenotypes from skin tumors to large brain tumors. Our lab has previously demonstrated that Tuberin can directly bind and regulate the timing of nuclear transport of the G2/M cyclin, Cyclin B1. Herein we study the consequence of one clinically relevant truncation in the Tuberin protein on cell cycle function. We demonstrate that exogenous expression of a fragment of the N-term region of Tuberin alters the subcellular localization of Cyclin B1 and increases cell proliferation. This adds to our body of information about the residues within Tuberin responsible for regulating the cytoplasmic retention of Cyclin B1 and supports the phenotypic data seen in the clinic with Tuberous Sclerosis Complex patients harbouring similar large deletions in Tuberin.
Assuntos
Esclerose Tuberosa , Ciclina B1/genética , Ciclinas , Humanos , Proteínas Repressoras/genética , Esclerose Tuberosa/patologia , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Resumo Fundamento A COVID-19 adicionou um fardo enorme sobre os médicos ao redor do mundo, especialmente as mulheres médicas, que são afetadas pelo aumento da carga de trabalho e pela perda da qualidade de vida. Objetivo Avaliar os efeitos da pandemia de COVID-19 na qualidade de vida, burnout e espiritualidade de médicas brasileiras que atendem pacientes com COVID-19 direta ou indiretamente. Método Estudo prospectivo, observacional realizado de 28 de julho a 27 de setembro de 2020, no Brasil, com mulheres médicas de 47 especialidades, a mais frequente sendo a cardiologia (22,8%), sem restrição de idade. Elas responderam voluntariamente um questionário online com questões sobre características demográficas e socioeconômicas, qualidade de vida (WHOQOL-brief) e espiritualidade (WHOQOL-SRPB) e enunciados do Oldenburg Burnout Inventory. A análise estatística utilizou o software R, regressão beta, árvores de classificação e matriz de correlação policórica, com nível de significância de 5%. Resultados Das 769 respondentes, 61,6% relataram sinais de burnout. Cerca de 64% relataram perda salarial de até 50% durante a pandemia. Algumas relataram falta de energia para as tarefas diárias, sentimentos negativos frequentes, insatisfação com a capacidade para o trabalho, e que cuidar de outras pessoas não agregava sentido às suas vidas. Os sentimentos negativos correlacionaram-se negativamente com a satisfação com a vida sexual, a satisfação com as relações pessoais e a energia para as tarefas diárias. A incapacidade de permanecer otimista em tempos de incerteza correlacionou-se positivamente com a sensação de insegurança no dia a dia e com o não reconhecimento de que cuidar de outras pessoas trouxesse sentido à vida. Conclusão O presente estudo mostrou uma alta frequência de burnout entre as médicas brasileiras que responderam ao questionário durante a pandemia de COVID-19. Apesar disso, apresentavam uma qualidade de vida relativamente boa e acreditavam que a espiritualidade trazia-lhes conforto e segurança nos momentos difíceis.
Abstract Background COVID-19 has placed a tremendous burden on physicians worldwide, especially women physicians, affected by increased workload and loss of quality of life. Objective To assess the effects of the COVID-19 pandemic on the quality of life, burnout and spirituality of Brazilian women physicians directly or indirectly providing care to COVID-19 patients. Methods Prospective, observational study performed from July 28 to September 27, 2020, in Brazil, with women physicians from 47 specialities, the most frequent being cardiology (22.8%), with no age restriction. They voluntarily answered an online survey with questions on demographic and socioeconomic characteristics, quality of life (WHOQOL-brief), spirituality (WHOQOL-SRPB), and statements from the Oldenburg Burnout Inventory. Statistical analysis used the R software, beta regression, classification trees, and polychoric correlation matrix, with a 5% of significance level. Results Of the 769 respondents, 61.6% reported signs of burnout. About 64% reported wage loss of up to 50% during the pandemic. Some reported lack of energy for daily tasks, frequent negative feelings, dissatisfaction with capability for work, and caring for others not adding meaning to their lives. Negative feelings correlated negatively with satisfaction with sexual life and personal relations, and energy for daily tasks. The inability to remain optimistic in times of uncertainty correlated positively with feeling unsafe daily and not acknowledging that caring for others brings meaning to life. Conclusion This study showed a high frequency of burnout among Brazilian women physicians who answered the survey during the COVID-19 pandemic. Nevertheless, they presented with a relatively good quality of life and believed that spirituality comforted and reassured them in hard times.
RESUMO
OBJECTIVES: The study investigated the long-term functional status of hospitalised COVID-19 survivors to explore and document their functional situation. DESIGN: This prospective observational study assessed 801 COVID-19 survivors at 3-11 months after hospital discharge. It analyses participants' sociodemographic background, COVID-19 clinical manifestations, and clinical and functional evaluations. SETTING: Tertiary-level university hospital in São Paulo, Brazil. PARTICIPANTS: Study participants are COVID-19 survivors admitted to hospital care for at least 24 hours to treat acute SARS-CoV-2 infection. OUTCOME MEASURES: Epworth Sleepiness Scale, EuroQoL-5 Dimensions-5 Levels, Functional Assessment of Chronic Illness Therapy-Fatigue, Functional Independence Measure, Functional Oral Intake Scale, Handgrip Strength, Insomnia Severity Index, Medical Research Council (MRC) Dyspnea Scale, MRC sum score, Modified Borg Dyspnea Scale, pain Visual Analogue Scale, Post-COVID-19 Functional Status, Timed Up and Go, WHO Disability Assessment Schedule 2.0, 1-Minute Sit to Stand Test. RESULTS: Many participants required invasive mechanical ventilation (41.57%, 333 of 801). Mean age was 55.35±14.58 years. With a mean of 6.56 (SD: 1.58; 95% CI: 6.45 to 6.67) months after hospital discharge, 70.86% (567 of 800) reported limited daily activities, which were severe in 5.62% (45 of 800). They also reported pain and discomfort (64.50%, 516 of 800), breathlessness (64.66%, 514 of 795), and anxiety and depression (57.27%, 457 of 798). Daytime sleepiness and insomnia evaluations showed subthreshold results. Most (92.85%, 727 of 783) participants reported unrestricted oral intake. Data indicated no generalised fatigue (mean score: 39.18, SD: 9.77; 95% CI: 38.50 to 39.86). Assessments showed poor handgrip strength (52.20%, 379 of 726) and abnormal Timed Up and Go results (mean 13.07 s, SD: 6.49). The invasive mechanical ventilation group seemed to have a better handgrip strength however. We found no clear trends of change in their functional status during months passed since hospital discharge. CONCLUSIONS: Muscle weakness, pain, anxiety, depression, breathlessness, reduced mobility, insomnia and daytime sleepiness were the most prevalent long-term conditions identified among previously hospitalised COVID-19 survivors.
Assuntos
COVID-19 , Distúrbios do Sono por Sonolência Excessiva , Distúrbios do Início e da Manutenção do Sono , Adulto , Idoso , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/terapia , Dispneia , Fadiga/epidemiologia , Fadiga/etiologia , Força da Mão , Hospitalização , Humanos , Pessoa de Meia-Idade , Dor , SARS-CoV-2 , SobreviventesRESUMO
BACKGROUND: COVID-19 has placed a tremendous burden on physicians worldwide, especially women physicians, affected by increased workload and loss of quality of life. OBJECTIVE: To assess the effects of the COVID-19 pandemic on the quality of life, burnout and spirituality of Brazilian women physicians directly or indirectly providing care to COVID-19 patients. METHODS: Prospective, observational study performed from July 28 to September 27, 2020, in Brazil, with women physicians from 47 specialities, the most frequent being cardiology (22.8%), with no age restriction. They voluntarily answered an online survey with questions on demographic and socioeconomic characteristics, quality of life (WHOQOL-brief), spirituality (WHOQOL-SRPB), and statements from the Oldenburg Burnout Inventory. Statistical analysis used the R software, beta regression, classification trees, and polychoric correlation matrix, with a 5% of significance level. RESULTS: Of the 769 respondents, 61.6% reported signs of burnout. About 64% reported wage loss of up to 50% during the pandemic. Some reported lack of energy for daily tasks, frequent negative feelings, dissatisfaction with capability for work, and caring for others not adding meaning to their lives. Negative feelings correlated negatively with satisfaction with sexual life and personal relations, and energy for daily tasks. The inability to remain optimistic in times of uncertainty correlated positively with feeling unsafe daily and not acknowledging that caring for others brings meaning to life. CONCLUSION: This study showed a high frequency of burnout among Brazilian women physicians who answered the survey during the COVID-19 pandemic. Nevertheless, they presented with a relatively good quality of life and believed that spirituality comforted and reassured them in hard times.
FUNDAMENTO: A COVID-19 adicionou um fardo enorme sobre os médicos ao redor do mundo, especialmente as mulheres médicas, que são afetadas pelo aumento da carga de trabalho e pela perda da qualidade de vida. OBJETIVO: Avaliar os efeitos da pandemia de COVID-19 na qualidade de vida, burnout e espiritualidade de médicas brasileiras que atendem pacientes com COVID-19 direta ou indiretamente. MÉTODO: Estudo prospectivo, observacional realizado de 28 de julho a 27 de setembro de 2020, no Brasil, com mulheres médicas de 47 especialidades, a mais frequente sendo a cardiologia (22,8%), sem restrição de idade. Elas responderam voluntariamente um questionário online com questões sobre características demográficas e socioeconômicas, qualidade de vida (WHOQOL-brief) e espiritualidade (WHOQOL-SRPB) e enunciados do Oldenburg Burnout Inventory. A análise estatística utilizou o software R, regressão beta, árvores de classificação e matriz de correlação policórica, com nível de significância de 5%. RESULTADOS: Das 769 respondentes, 61,6% relataram sinais de burnout. Cerca de 64% relataram perda salarial de até 50% durante a pandemia. Algumas relataram falta de energia para as tarefas diárias, sentimentos negativos frequentes, insatisfação com a capacidade para o trabalho, e que cuidar de outras pessoas não agregava sentido às suas vidas. Os sentimentos negativos correlacionaram-se negativamente com a satisfação com a vida sexual, a satisfação com as relações pessoais e a energia para as tarefas diárias. A incapacidade de permanecer otimista em tempos de incerteza correlacionou-se positivamente com a sensação de insegurança no dia a dia e com o não reconhecimento de que cuidar de outras pessoas trouxesse sentido à vida. CONCLUSÃO: O presente estudo mostrou uma alta frequência de burnout entre as médicas brasileiras que responderam ao questionário durante a pandemia de COVID-19. Apesar disso, apresentavam uma qualidade de vida relativamente boa e acreditavam que a espiritualidade trazia-lhes conforto e segurança nos momentos difíceis.
Assuntos
Esgotamento Profissional , COVID-19 , Pandemias , Médicas , Brasil/epidemiologia , Esgotamento Profissional/epidemiologia , COVID-19/epidemiologia , COVID-19/terapia , Feminino , Humanos , Médicas/psicologia , Estudos Prospectivos , Qualidade de Vida , Espiritualidade , Inquéritos e QuestionáriosRESUMO
Background: Black women in the United States disproportionately suffer adverse pregnancy and birth outcomes compared to White women. Economic adversity and implicit bias during clinical encounters may lead to physiological responses that place Black women at higher risk for adverse birth outcomes. The novel coronavirus disease of 2019 (COVID-19) further exacerbated this risk, as safety protocols increased social isolation in clinical settings, thereby limiting opportunities to advocate for unbiased care. Twitter, 1 of the most popular social networking sites, has been used to study a variety of issues of public interest, including health care. This study considers whether posts on Twitter accurately reflect public discourse during the COVID-19 pandemic and are being used in infodemiology studies by public health experts. Objective: This study aims to assess the feasibility of Twitter for identifying public discourse related to social determinants of health and advocacy that influence maternal health among Black women across the United States and to examine trends in sentiment between 2019 and 2020 in the context of the COVID-19 pandemic. Methods: Tweets were collected from March 1 to July 13, 2020, from 21 organizations and influencers and from 4 hashtags that focused on Black maternal health. Additionally, tweets from the same organizations and hashtags were collected from the year prior, from March 1 to July 13, 2019. Twint, a Python programming library, was used for data collection and analysis. We gathered the text of approximately 17,000 tweets, as well as all publicly available metadata. Topic modeling and k-means clustering were used to analyze the tweets. Results: A variety of trends were observed when comparing the 2020 data set to the 2019 data set from the same period. The percentages listed for each topic are probabilities of that topic occurring in our corpus. In our topic models, tweets on reproductive justice, maternal mortality crises, and patient care increased by 67.46% in 2020 versus 2019. Topics on community, advocacy, and health equity increased by over 30% in 2020 versus 2019. In contrast, tweet topics that decreased in 2020 versus 2019 were as follows: tweets on Medicaid and medical coverage decreased by 27.73%, and discussions about creating space for Black women decreased by just under 30%. Conclusions: The results indicate that the COVID-19 pandemic may have spurred an increased focus on advocating for improved reproductive health and maternal health outcomes among Black women in the United States. Further analyses are needed to capture a longer time frame that encompasses more of the pandemic, as well as more diverse voices to confirm the robustness of the findings. We also concluded that Twitter is an effective source for providing a snapshot of relevant topics to guide Black maternal health advocacy efforts.
RESUMO
Asprosin is a fasting-induced glucogenic and centrally acting orexigenic hormone. The olfactory receptor Olfr734 is known to be the hepatic receptor for asprosin that mediates its effects on glucose production, but the receptor for asprosin's orexigenic function has been unclear. Here, we have identified protein tyrosine phosphatase receptor δ (Ptprd) as the orexigenic receptor for asprosin. Asprosin functions as a high-affinity Ptprd ligand in hypothalamic AgRP neurons, regulating the activity of this circuit in a cell-autonomous manner. Genetic ablation of Ptprd results in a strong loss of appetite, leanness, and an inability to respond to the orexigenic effects of asprosin. Ablation of Ptprd specifically in AgRP neurons causes resistance to diet-induced obesity. Introduction of the soluble Ptprd ligand-binding domain in the circulation of mice suppresses appetite and blood glucose levels by sequestering plasma asprosin. Identification of Ptprd as the orexigenic asprosin receptor creates a new avenue for the development of anti-obesity therapeutics.
Assuntos
Hormônios Peptídicos , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores , Proteína Relacionada com Agouti , Animais , Fibrilina-1/metabolismo , Glucose/metabolismo , Ligantes , Camundongos , Obesidade/metabolismo , Fragmentos de Peptídeos/metabolismo , Hormônios Peptídicos/genética , Hormônios Peptídicos/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismoRESUMO
Objetivo: descrever a experiência da Supervisão de Enfermagem em um hospital universitário no município do Rio de Janeiro, frente à pandemia da covid-19. Método: estudo qualitativo, descritivo, tipo relato de experiência, baseado na vivência dos autores e na análise de documentos entre março e dezembro de 2020. Resultados: a pandemia acrescentou desafios ao trabalho da supervisão, além daqueles inerentes a instituição. O aumento e a especificidade da demanda provocaram um refinamento na atuação do grupo no intuito de otimizar processos e servindo como elo entre pacientes, equipe e instituição. Conclusão: é fundamental dar voz ao corpo da Enfermagem e à clientela, para a construção de uma prática ética, ancorada na ciência, contextualizada nas esferas social, histórica e política, com um olhar atento ao ambiente de trabalho, tratando com respeito os problemas do cotidiano hospitalar, tangenciado pela pandemia de covid-19(AU)
Objective: to describe the experience of Nursing Supervision in a university hospital in the city of Rio de Janeiro, facing the COVID-19 pandemic. Method: qualitative, descriptive study, experience report type, based on the authors' experience and on the analysis of documents between March and December 2020. Results: the pandemic added challenges to the work of supervision, in addition to those inherent to the institution. The increase and specificity of demand led to a refinement in the group's performance in order to optimize processes and serving as a link between patients, staff and institution. Conclusion: it is essential to give a voice to the Nursing body and the clientele, for the construction of an ethical practice, anchored in science, contextualized in the social, historical and political spheres, with an attentive look at the work environment, dealing with problems with respect hospital routine, affected by the COVID-19 pandemic.(AU)
Objetivo: describir la experiencia de Supervisión de Enfermería en un hospital universitario de la ciudad de Río de Janeiro, frente a la pandemia COVID-19. Método: estudio cualitativo, descriptivo, tipo relato de experiencia, basado en la experiencia de los autores y en el análisis de documentos entre marzo y diciembre de 2020. Resultados: la pandemia agregó desafíos a la supervisión, además de los inherentes a la institución. El aumento y la especificidad de la demanda han perfeccionado el desempeño del grupo para optimizar los procesos y servir de vínculo entre los pacientes, el personal y la institución. Conclusión: es fundamental dar voz al cuerpo de Enfermería y a la clientela, construyendo una práctica ética, anclada en la ciencia, contextualizada en los ámbitos social, histórico y político, con una mirada atenta al entorno laboral, abordando la problemática de la vida diaria hospitalaria con respeto, tocada por la pandemia COVID-19(AU)
Assuntos
Supervisão de Enfermagem , Governança Compartilhada de Enfermagem , COVID-19RESUMO
Abstract Aim: This narrative review aimed to explore the effect of mental fatigue on physical, technical, and tactical performance in ball sports. Methods: Three Databases, PUBMED, SCOPUS, and SCIELO, were used to search for a scientific publication. The criterions adopted were: a) published in a peer-reviewed journal; b) adopted at least one manipulation check related to mental fatigue; c) mental fatigue induced by a cognitive task before the outcome task, and d) study participants were ball sports athletes. Result: The quality of this narrative review was rated at 11 (SANRA scale 0-12), and the papers analyzed were published between 2015 and 2022. Twenty-one experimental studies were included in this review. Most studies were in invasion sports (n = 13; 72%), and non-ecological tasks were used to induce mental fatigue (n = 15; 83%). Regarding performance in endurance tests, mentally fatigued athletes had performance impaired. However, when assessed during a small-sided or simulated game, data were inconclusive within the literature. Moreover, athletes presented attenuated perceptual skills (e.g., visual field). Consequently, this worsened motor skills, technical-tactical performances, and tactical behavior. Conclusions: Cognitively demanding tasks should be avoided before training and sports competitions because they can lead the athlete to mental fatigue and impair performance. This impairment is identified in physical performance (endurance tasks) and technical and tactical performance. Finally, it is recommended that athletes do not perform tasks that cause mental fatigue 2 h before the sports event.
Assuntos
Humanos , Esportes , Desempenho Atlético , Fadiga Mental , Neurociência Cognitiva , Psicologia do EsporteRESUMO
The COVID-19 pandemic qualifies as a major national and global disaster. Behavioral health providers are poised to provide psychological crisis interventions to reduce the psychosocial effects. This paper presents a brief transdiagnostic mental health maintenance intervention tailored to treat adults and families with distress symptoms as a consequence of the ongoing COVID-19 pandemic. The intervention components include evidence-based techniques which have been strategically selected to address mental health distress related to the pandemic and to prevent the escalation of distress as the pandemic continues. The intervention aims to be flexibly incorporated into care based on the provider and needs of the presenting individuals. The intervention incorporates components of evidence-based treatments such as Cognitive Behavioral Therapy and associated "third wave" therapies (e.g. Dialectical Behavioral Therapy and Acceptance and Commitment Therapy). The intervention can be delivered via telehealth and includes the following modules: 1) Agenda Setting & Avoidance Identification; 2) Responding to Difficult News/Normalizing Reactions; 3) Perspective Taking; 4) Situational Control/Acceptance; 5) Maintaining a Healthy Routine; 6) Coping with Stress; 7) Insomnia Preventions; and 8) Building Resiliency & Hope. A list of pleasurable activities that can be completed at home and technology modalities to maintain social interactions is included. The intervention also includes the Pandemic Mental Health Maintenance Intervention handout to provide to patients. Research is needed to test this intervention in a randomized controlled trial and assess efficacious intervention implementation strategies.
RESUMO
OBJECTIVE: This study aimed to analyze the physical and pulmonary capacities of hospitalized patients with severe coronavirus disease and its correlation with the time of hospitalization and complications involved. METHODS: A total of 54 patients, aged ≥18 years of both sexes, were evaluated 2-4 months after hospital discharge in São Paulo, Brazil. The physical characteristics analyzed were muscle strength, balance, flexibility, and pulmonary function. The K-means cluster algorithm was used to identify patients with similar physical and pulmonary capacities, related to the time of hospitalization. RESULTS: Two clusters were derived using the K-means algorithm. Patients allocated in cluster 1 had fewer days of hospitalization, intensive care, and intubation than those in cluster 2, which reflected a better physical performance, strength, balance, and pulmonary condition, even 2-4 months after discharge. Days of hospitalization were inversely related to muscle strength, physical performance, and lung function: hand grip D (r=-0.28, p=0.04), Short Physical Performance Battery score (r=-0.28, p=0.03), and forced vital capacity (r=-0.29, p=0.03). CONCLUSION: Patients with a longer hospitalization time and complications progressed with greater loss of physical and pulmonary capacities.
Assuntos
Coronavirus , Alta do Paciente , Adolescente , Adulto , Brasil , Análise por Conglomerados , Estudos Transversais , Feminino , Força da Mão , Hospitalização , Hospitais , Humanos , Pulmão , MasculinoRESUMO
Fully differentiated cells can be reprogrammed through ectopic expression of key transcription factors to create induced pluripotent stem cells. These cells share many characteristics of normal embryonic stem cells and have great promise in disease modeling and regenerative medicine. The process of remodeling has its limitations, including a very low efficiency due to the upregulation of many antiproliferative genes, including cyclin dependent kinase inhibitors CDKN1A and CDKN2A, which serve to protect the cell by inducing apoptotic and senescent programs. Our data reveals a unique cell cycle mechanism enabling mouse fibroblasts to repress cyclin dependent kinase inhibitors through the activation of the epigenetic regulator EZH2 by a cyclin-like protein SPY1. This data reveals that the SPY1 protein is required for reprogramming to a pluripotent state and is capable of increasing reprogramming efficiency.
Assuntos
Histonas , Células-Tronco Pluripotentes Induzidas , Animais , Reprogramação Celular/genética , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Células-Tronco Embrionárias/metabolismo , Fibroblastos/metabolismo , Histonas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , CamundongosRESUMO
BACKGROUND: Experiencing a pandemic can be very unsettling and may have a negative impact on the mental health of frontline healthcare workers (HCWs). This may have serious consequences for the overall well-being of HCWs, which in turn may adversely affect patient safety and the productivity of the institution. AIMS: We designed a study to assess the prevalence of generalised anxiety disorder (GAD), depression and work-related stress experienced by the National Health Service staff in a large tertiary London hospital treating patients with COVID-19 during the current active phase of the COVID-19 era. METHODS: An anonymous survey was designed with demographic data and three questionnaires. The Generalised Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 were used to assess anxiety and depression, respectively. The Health and Safety Executive Management Standards Indicator Tool was used to assess work-related stress. Staff from multiple specialties embracing cardiothoracic surgery, cardiology, respiratory medicine, endocrinology, oncology, imaging, anaesthesia and intensive care at our hospital were asked to complete the questionnaire between 25 May and 15 June 2020. RESULTS: A total of 302 staff members (106 males and 196 females) completed the survey. The overall prevalence of GAD and depression was 41.4% and 42.7%, respectively. The prevalence of GAD and depression was significantly higher in females than in males and was statistically significant. Nurses were four times more likely to report moderate to severe levels of anxiety and depression as compared with doctors. Work-related stress was also observed to be prevalent in our surveyed population with the following standards: relationships, role, control and change showing a need for improvement. CONCLUSIONS: Our study presents early evidence suggestive of a high prevalence of GAD, depression and work-related stress in HCWs. It is imperative that coherent strategies are implemented to improve the healthcare work environment during this pandemic and mitigate further injury to the mental health status of the healthcare population.
RESUMO
COVID-19 is a public health crisis that has fundamentally altered health care provision. The purpose of this study was to examine the impact of COVID-19 on pre-exposure prophylaxis (PrEP) care. We reviewed all patient records for those who presented for PrEP care at a PrEP program in Providence, Rhode Island from September 1st, 2019 to May 29th, 2020. The number of PrEP encounters decreased but was not significantly different over time (ps > .05). Patients were still able to access PrEP clinical services during the COVID-19 pandemic. Implementing flexible and timely PrEP delivery approaches in this setting likely minimized the disruption of PrEP care during COVID-19.
RESUMEN: COVID-19 es una crisis de salud pública que ha alterado fundamentalmente la prestación de servicios de salud. El propósito de este estudio fue examinar el impacto de COVID-19 en los servicios de la profilaxis preexposición (PrEP). Revisamos todos los registros de pacientes que se presentaron para recibir atención de PrEP en un programa de PrEP en Providence, Rhode Island desde el 1 de septiembre de 2019 hasta el 29 de mayo de 2020. El número de encuentros de PrEP disminuyó pero no fue significativamente diferente con el paso del tiempo (ps > .05). Los pacientes aún pudieron acceder a los servicios clínicos de PrEP durante la pandemia de COVID-19. La implementación de enfoques de entrega de PrEP que eran flexibles y oportunos en este entorno probablemente minimizó la interrupción de la atención médica de la PrEP durante COVID-19.