Impact of COVID-19 vaccination on clinical outcomes in kidney transplant patients.

INTRODUCTION: The global health crisis caused by the COVID-19 pandemic has resulted in severe mortality and morbidity. Immunosuppressed patients, such as kidney transplant recipients, are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. OBJECTIVE: The aim of this cohort study was to evaluate the impact of COVID-19 vaccination on clinical outcomes in patients with kidney transplants. MATERIALS AND METHODS: In this retrospective study, 254 patients with kidney transplants were vaccinated against SARS-CoV-2 and a fraction of these contracted COVID-19. The diagnosis of COVID-19 was carried out by reverse transcriptase-polymerase chain reaction testing, and the patients received treatment involving immunosuppressive and COVID-19-specific protocols. RESULTS: SARS-CoV-2 infection was diagnosed in 38 (14.96%) patients before the COVID-19 vaccine was administered. After vaccination, an additional 29 (11.42%) patients were diagnosed with COVID-19. Risk factors for hospitalization included age, body mass index (BMI), comorbidities, and time elapsed since renal transplantation (p = 0.025, 0.038, 0.012, and 0.046, respectively). COVID-19 vaccination resulted in a significant decrease in the rate of hospital-acquired SARS-CoV-2 infection from 63.16% to 34.48% (p = 0.020). The proportion of patients from this cohort placed in intensive care units decreased from 23.68% to zero. Allograft rejections exhibited a decreasing trend from 13.16% to 6.90% (p = 0.690). This patient cohort displayed 15.79% mortality prior to COVID-19 vaccination that was reduced to nil after immunization. CONCLUSION: COVID-19 vaccination significantly reduced COVID-19 severity and mortality in this cohort of patients with kidney transplants. The risk factors for hospitalization were determined to be age, BMI, comorbidities, and time since renal transplantation. COVID-19 vaccination resulted in a clinical outcome of reduced hospitalization and a decrease in clinical complications. The COVID-19 vaccination-derived adverse effects in this cohort were found to be comparable to those in the immunocompetent population.

Ghrelin delays premature aging in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition that arises from a single nucleotide alteration in the LMNA gene, leading to the production of a defective lamin A protein known as progerin. The accumulation of progerin accelerates the onset of a dramatic premature aging phenotype in children with HGPS, characterized by low body weight, lipodystrophy, metabolic dysfunction, skin, and musculoskeletal age-related dysfunctions. In most cases, these children die of age-related cardiovascular dysfunction by their early teenage years. The absence of effective treatments for HGPS underscores the critical need to explore novel safe therapeutic strategies. In this study, we show that treatment with the hormone ghrelin increases autophagy, decreases progerin levels, and alleviates other cellular hallmarks of premature aging in human HGPS fibroblasts. Additionally, using a HGPS mouse model (LmnaG609G/G609G mice), we demonstrate that ghrelin administration effectively rescues molecular and histopathological progeroid features, prevents progressive weight loss in later stages, reverses the lipodystrophic phenotype, and extends lifespan of these short-lived mice. Therefore, our findings uncover the potential of modulating ghrelin signaling offers new treatment targets and translational approaches that may improve outcomes and enhance the quality of life for patients with HGPS and other age-related pathologies.

Ataxin-2 in the hypothalamus at the crossroads between metabolism and clock genes.

ATXN2 gene, encoding for ataxin-2, is located in a trait locus for obesity. Atxn2 knockout (KO) mice are obese and insulin resistant; however, the cause for this phenotype is still unknown. Moreover, several findings suggest ataxin-2 as a metabolic regulator, but the role of this protein in the hypothalamus was never studied before. The aim of this work was to understand if ataxin-2 modulation in the hypothalamus could play a role in metabolic regulation. Ataxin-2 was overexpressed/re-established in the hypothalamus of C57Bl6/Atxn2 KO mice fed either a chow or a high-fat diet (HFD). This delivery was achieved through stereotaxic injection of lentiviral vectors encoding for ataxin-2. We show, for the first time, that HFD decreases ataxin-2 levels in mouse hypothalamus and liver. Specific hypothalamic ataxin-2 overexpression prevents HFD-induced obesity and insulin resistance. Ataxin-2 re-establishment in Atxn2 KO mice improved metabolic dysfunction without changing body weight. Furthermore, we observed altered clock gene expression in Atxn2 KO that might be causative of metabolic dysfunction. Interestingly, ataxin-2 hypothalamic re-establishment rescued these circadian alterations. Thus, ataxin-2 in the hypothalamus is a determinant for weight, insulin sensitivity and clock gene expression. Ataxin-2's potential role in the circadian clock, through the regulation of clock genes, might be a relevant mechanism to regulate metabolism. Overall, this work shows hypothalamic ataxin-2 as a new player in metabolism regulation, which might contribute to the development of new strategies for metabolic disorders.

Binge Eating and Compulsive Buying During Cabergoline Treatment for Prolactinoma: A Case Report.

Prolactinomas are the most prevalent functional pituitary adenomas. They are usually treated clinically with dopamine agonists. The most widely used and suitable drug is cabergoline (CAB), a specific D2 dopamine agonists. Patients in prolactinoma treatment with CAB commonly report physical side effects, but aberrant behavioral changes such as increased impulsivity have also been reported recently. We report the case of a 47-year-old Brazilian woman with prolactinoma that developed compulsive buying, binge eating, and hypersexuality after four years of CAB treatment. In her psychiatric evaluation, the patient scored high levels on the following scales: Compulsive Buying Scale (CBS), Binge Eating Scale (BES), and Barratt Impulsiveness Scale-11 (BIS11). She also reported financial problems and weight gain in addition to her social and clinical problems. Impulsivity disorders may appear with the use of CAB and other dopamine agonists. We suggest that more observational studies with a large patient sample and specific regular psychiatric evaluations during treatment are necessary for patients in use of CAB, especially those treated for several years.

Depression associated variables among lower limb amputees in Santa Catarina State - Brazil / Fatores associados à depressão em pacientes amputados de membros inferiores no Estado de Santa Catarina - Brasil

The amputation of the lower limbs and depression has been studied by different groups with a wide prevalence range and some variables were related to depressive symptoms. Depression and anxiety have been related with a major impact on adherence to rehabilitation, functional prognosis, and quality of life. Knowing the patients at highest odds of presenting depressive symptoms may favor an early approach and treatment, ultimately optimizing the rehabilitation process and social reintegration. Depression can be related to a lower rate of adaptation to the prosthesis and its use. Objective: To determine the association among demographic, socioeconomic, clinical variables with depressive symptoms in amputees before the prosthetic adaptation. Methods: A case-control study was performed to analyze variables associated with depression (Beck Depression Inventory-II) in lower limb amputees. Results: Patients with previous depression (OR= 17,08; CI95:2,14-136,28) and low socioeconomic class (OR= 3,04; CI95:1,24-7,47) are at highest odds of depression after amputation in the state of Santa Catarina. The model explained 71,4% of cases, classifying 88,1% of negative and 23,8% of positive cases. According to our model amputees recruited rarely presented the diagnosis of depression if they belong to a higher socioeconomic class and have no previous depression. On the other hand, patients who presented Brazilian low socioeconomic class D-E, and previous depression should be referenced to a psychological evaluation because they have a chance of depression, close to 1 in 4 cases. Conclusion: Previous depression and low social class were associated with the highest odds of depression after amputation in our population.

Sintomas depressivos em pacientes com amputação de membros inferiores foram foco de diversos estudos, com amplos intervalos de prevalência encontrados, e algumas variáveis foram relacionadas com os sintomas depressivos. Depressão e ansiedade têm grande impacto na aderência à reabilitação, no prognóstico funcional e na qualidade de vida. Conhecer os pacientes que têm maior risco de apresentar sintomas depressivos pode favorecer uma abordagem precoce e seu tratamento, potencializando a reabilitação, a reinserção social, a adaptação à prótese e seu uso. Objetivo: Determinar associação entre fatores demográficos, socioeconômicos, e clínicos com sintomas depressivos em pacientes amputados antes da protetização. Métodos: Estudo tipo caso-controle para avaliar fatores associados - dados demográficos, socioeconômicos e comorbidades - à depressão (utilizando escala de depressão de Beck-II) em pacientes com amputação de membro inferior. Resultados: Pacientes com depressão prévia (OR= 17,08, IC95:2,14-136,28) e baixa classe social (OR= 3,04, IC95:1,24-7,47) apresentam alta chance de depressão após amputação em Santa Catarina. O modelo explica 71.4% dos casos, classificando adequadamente 88,1% dos negativos e 23,8% dos positivos. E encontrou-se maior capacidade de predizer casos negativos - amputados raramente apresentaram diagnóstico de depressão se pertenciam a uma classe social mais alta e se não tinham diagnóstico prévio de depressão. Pacientes de classes sociais D-E, e diagnóstico prévio de depressão devem ser referenciados para avaliação psicológica devido à chance de depressão próxima de 1 a cada 4 casos. Conclusão: Depressão prévia à amputação e classes sociais mais baixas apresentaram maior chance de desenvolver sintomas depressivos após amputação na população estudada.

Faux Pas Recognition Test: transcultural adaptation and evaluation of its psychometric properties in Brazil.

Introduction: Many neuropsychiatric and neurodegenerative disorders produce Theory of Mind impairment. We aimed to implement a Brazilian Portuguese version of the Faux Pas Recognition Test (FPRT) and evaluate its psychometric properties.Methods: We first completed an English-Brazilian Portuguese translation and adaptation to obtain an FPRT Brazilian Portuguese version. We performed a multicentric study with 153 healthy participants (68.6% women), mean age of 38.8 years (SD = 14.6) and 12.9 years of schooling (SD = 4.5). Linear regression analysis was performed to evaluate the association of social class, age, schooling, and FPRT scores. The psychometric analyses comprised item analysis, exploratory factor analysis, reliability, and validity analysis.Results: Normative data in a Brazilian population is presented. A positive correlation of scores with years of schooling, social class, and an inverse relation with age was found. The exploratory factorial analysis found a two-component structure, one component, consisting of questions 1 through 6 (Eigenvalue 5.325) and another component, consisting of questions 7 and 8 (Eigenvalue 1.09). Cronbach's alpha of the 20 stories was .72. All control stories had a poor discriminative index.Conclusion: The FPRT Brazilian Portuguese version demonstrated good internal consistency and, psychometric properties and is adequate for use even in lower educational contexts in Brazil.

Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation.

Caloric restriction is an anti-aging intervention known to extend lifespan in several experimental models, at least in part, by stimulating autophagy. Caloric restriction increases neuropeptide Y (NPY) in the hypothalamus and plasma ghrelin, a peripheral gut hormone that acts in hypothalamus to modulate energy homeostasis. NPY and ghrelin have been shown to be neuroprotective in different brain areas and to induce several physiological modifications similar to those induced by caloric restriction. However, the effect of NPY and ghrelin in autophagy in cortical neurons is currently not known. Using a cell culture of rat cortical neurons we investigate the involvement of NPY and ghrelin in caloric restriction-induced autophagy. We observed that a caloric restriction mimetic cell culture medium stimulates autophagy in rat cortical neurons and NPY or ghrelin receptor antagonists blocked this effect. On the other hand, exogenous NPY or ghrelin stimulate autophagy in rat cortical neurons. Moreover, NPY mediates the stimulatory effect of ghrelin on autophagy in rat cortical neurons. Since autophagy impairment occurs in aging and age-related neurodegenerative diseases, NPY and ghrelin synergistic effect on autophagy stimulation may suggest a new strategy to delay aging process.

Neuropeptide Y: An Anti-Aging Player?

Accumulating evidence suggests that neuropeptide Y (NPY) has a role in aging and lifespan determination. In this review, we critically discuss age-related changes in NPY levels in the brain, together with recent findings concerning the contribution of NPY to, and impact on, six hallmarks of aging, specifically: loss of proteostasis, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing, cellular senescence, and mitochondrial dysfunction. Understanding how NPY contributes to, and counteracts, these hallmarks of aging will open new avenues of research on limiting damage related to aging.

NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging?

Aging was recently described as a life event programmed by the hypothalamus, a key brain region that is crucial for the neuroendocrine interaction between the central nervous system and the periphery. Autophagy impairment is a hallmark of aging, contributing to the aging phenotype and to the aggravation of age-related diseases. Since hypothalamic autophagy decreases with age, strategies to promote autophagy in the hypothalamus may be relevant for control of the aging process. NPY (neuropeptide Y) is an endogenous neuropeptide mainly produced by the hypothalamus. We recently reported, for the first time, that NPY stimulates autophagy in rodent hypothalamus and mediates caloric restriction-induced autophagy in hypothalamic neurons. Moreover, we observed that NPY acts through NPY1R (neuropeptide Y receptor Y1) or NPY5R activation involving a concerted action of different signaling pathways. Since both hypothalamic autophagy and NPY levels decrease with age, modulation of NPY levels could provide new putative therapeutic tools to ameliorate age-related deteriorations and extend longevity.

Neuropeptide Y stimulates autophagy in hypothalamic neurons.

Aging is characterized by autophagy impairment that contributes to age-related disease aggravation. Moreover, it was described that the hypothalamus is a critical brain area for whole-body aging development and has impact on lifespan. Neuropeptide Y (NPY) is one of the major neuropeptides present in the hypothalamus, and it has been shown that, in aged animals, the hypothalamic NPY levels decrease. Because caloric restriction (CR) delays aging, at least in part, by stimulating autophagy, and also increases hypothalamic NPY levels, we hypothesized that NPY could have a relevant role on autophagy modulation in the hypothalamus. Therefore, the aim of this study was to investigate the role of NPY on autophagy in the hypothalamus. Using both hypothalamic neuronal in vitro models and mice overexpressing NPY in the hypothalamus, we observed that NPY stimulates autophagy in the hypothalamus. Mechanistically, in rodent hypothalamic neurons, NPY increases autophagy through the activation of NPY Y1 and Y5 receptors, and this effect is tightly associated with the concerted activation of PI3K, MEK/ERK, and PKA signaling pathways. Modulation of hypothalamic NPY levels may be considered a potential strategy to produce protective effects against hypothalamic impairments associated with age and to delay aging.

Fluoxetine induces proliferation and inhibits differentiation of hypothalamic neuroprogenitor cells in vitro.

A significant number of children undergo maternal exposure to antidepressants and they often present low birth weight. Therefore, it is important to understand how selective serotonin reuptake inhibitors (SSRIs) affect the development of the hypothalamus, the key center for metabolism regulation. In this study we investigated the proliferative actions of fluoxetine in fetal hypothalamic neuroprogenitor cells and demonstrate that fluoxetine induces the proliferation of these cells, as shown by increased neurospheres size and number of proliferative cells (Ki-67+ cells). Moreover, fluoxetine inhibits the differentiation of hypothalamic neuroprogenitor cells, as demonstrated by decreased number of mature neurons (Neu-N+ cells) and increased number of undifferentiated cells (SOX-2+ cells). Additionally, fluoxetine-induced proliferation and maintenance of hypothalamic neuroprogenitor cells leads to changes in the mRNA levels of appetite regulator neuropeptides, including Neuropeptide Y (NPY) and Cocaine-and-Amphetamine-Regulated-Transcript (CART). This study provides the first evidence that SSRIs affect the development of hypothalamic neuroprogenitor cells in vitro with consequent alterations on appetite neuropeptides.

Representação social dos temas saúde e meio ambiente na sociedade civil do Fórum Comperj, Itaboraí, RJ / Social representation of health and environment issues in civil society Forum Comperj, Itaboraí, RJ

O Complexo Petroquímico do Rio de Janeiro (COMPERJ) está sendo construído em Itaboraí (estado do Rio de Janeiro) e ocupará uma área total de 45 Km2. Sua área industrial irá abranger 26 por cento da área total. É o maior projeto individual da história daPetrobras. Sua previsão de operação é em 2014 e objetiva, à partir desta data, processar em torno de 165 mil barris de óleo pesado nacional por dia na primeira unidade de refino. Em 2017 ou 2018 serão mais 165 milhões de barris por dia na segunda unidade de refino. Por seu tamanho e complexidade, o empreendimento trará impactos diretos eindiretos em outros espaços territoriais que não Itaboraí. Para “ajudar a sociedade a maximizar os benefícios e amenizar ou compensar impactos desfavoráveis do empreendimento” foi criado o Fórum Permanente para oDesenvolvimento da Área de Influência do COMPERJ (Fórum COMPERJ). Este Fórum foi utilizado no estudo para trazer à tona a opinião dos vários segmentos envolvidos, investigando o discurso de inúmeros atores, como especialistas e tomadores de decisões, além dos “porta-vozes” legítimos. O objetivo desse trabalho é realizar a contextualização dos problemas ambientais e de saúde dentro de um estudo de caso, relacionando-os com suas dimensõeseconômicas, sociais, técnicas e éticas; contribuindo para o debate sobresustentabilidade, tanto no âmbito ambiental quanto da saúde levando em consideração o modelo econômico dominante. O tema Saúde e Ambiente, que relaciona as dimensões social e política (como o presente) apesar de sua relevância, não recebeu status necessário na produção científicamediante as transformações ocorridas na área recentemente em âmbito mundial. É necessário, portanto, trazer à tona o assunto e mostrar resultados contextualizados nas dimensões sócio-político-ambientais dos problemas, esclarecendo os fatores que osdesencadeiam e determinando as condições que devem cercar a ação de urgência. Para averiguar o discurso dos atores, foram aplicadas aos representantes da Sociedade Civil do Fórum COMPERJ (ONG’s, Indústria, Comércio e Universidade) entrevistas estruturadas, com perguntas abertas. Foram colhidos os depoimentos dos representantes do GTEG, FECOMERCIO, APEDEMA, SEBRAE, ONIP, FUP, FIRJAN e SENAI. A reconstituição das representações sociais foi dada sob a forma de Discursos do Sujeito Coletivo. O DSC é uma técnica, um modelo, um tipo de estratégia de obtenção da representação social, que tem como prioridade o resgate do coletivo. Para este trabalho foi criado o DSI, Discurso do Sujeito Individual. Foi concluído que o Fórum, apesar de ser uma excelente oportunidade de discussões que visam melhorias para a região de instalação do empreendimento relacionado a ele, não cumpriu seu papel de debatedor de idéias, já que não deu prosseguimento aos debates. Iniciativas como essas são muito boas, mas quando acontece algo ruim, como o fato de ter tido apenas uma reunião, torna desestimuladora ecansativa a luta social. Os representantes ficaram divididos quanto ao empreendimento. Uns pensam seralgo bom e outros, extremamente ruim. Há também quem pondera que, apesar dos riscos inerentes a empreendimentos como esse, o negócio vale a pena pelo progresso.