Post-COVID-19 cognitive symptoms in patients assisted by a teleassistance service: a retrospective cohort study.

Introduction: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people. Objective: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors. Methods: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied via phone calls, regarding the persistence of COVID-19 symptoms after 12 weeks of the disease. Cognitive symptoms were defined as any of the following: memory loss, problems concentrating, word finding difficulties, and difficulty thinking clearly. Results: From 630 patients who responded to the questionnaire, 23.7% presented cognitive symptoms at 12 weeks after infection. These patients had a higher median age (33 [IQR 25-46] vs. 30 [IQR 24-42] years-old, p = 0.042) with a higher prevalence in the female sex (80.5% vs. 62.2%, p < 0.001) when compared to those who did not present cognitive symptoms, as well as a lower prevalence of smoking (8.7% vs. 16.2%, p = 0.024). Furthermore, patients with persistent cognitive symptoms were more likely to have been infected during the second wave of COVID-19 rather than the third (31.0% vs. 21.3%, p = 0.014). Patients who needed to seek in-person care during the acute phase of the disease were more likely to report post-acute cognitive symptoms (21.5% vs. 9.3%, p < 0,001). In multivariate logistic regression analysis, cognitive symptoms were associated with female sex (OR 2.24, CI 95% 1.41-3.57), fatigue (OR 2.33, CI 95% 1.19-4.56), depression (OR 5.37, CI 95% 2.19-13.15) and the need for seek in-person care during acute COVID-19 (OR 2.23, CI 95% 1.30-3.81). Conclusion: In this retrospective cohort of patients with mostly mild COVID-19, cognitive symptoms were present in 23.7% of patients with COVID-19 at 12 weeks after infection. Female sex, fatigue, depression and the need to seek in-person care during acute COVID-19 were the risk factors independently associated with this condition.

Effect of smoking on Brain-Derived Neurotrophic Factor (BDNF) blood levels: A systematic review and meta-analysis.

BACKGROUND: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that plays a crucial role in neuronal survival and plasticity. Previous studies have suggested that smoking may influence BDNF levels, but the findings have been inconsistent. METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the relationship between smoking and blood levels of BDNF. A random-effects model was used to estimate the overall effect size. RESULTS: A total of 23 studies were included. The meta-analysis revealed a significant association between smoking and increased blood levels of BDNF (standardized mean difference [SMD] = -0.38, 95 % confidence interval [CI] 0.15 to 0.62, p = 0.002). Subgroup analyses based on BDNF source showed a significant increase in plasma-derived BDNF levels (SMD = 1.02, 95 % CI 0.50 to 1.53, p = 0.0001), while no significant difference was observed in serum-derived BDNF levels (SMD = 0.02, 95 % CI -0.19 to 0.22, p = 0.87). The pooled analysis revealed a non-significant difference in blood levels of BDNF between former smokers and non-smokers (random-effects model, SMD = 0.21, 95 % CI -0.04 to 0.46, p = 0.1). CONCLUSION: Smokers exhibited significantly higher plasma levels of BDNF compared to non-smokers. Further research is needed to elucidate the underlying mechanisms and explore the potential therapeutic implications of targeting BDNF in smoking.

Independência funcional, aspectos clínicos e fatores sociodemográficos em pacientes na fase aguda do Acidente Vascular Cerebral: uma análise de associação / Functional independence, clinical aspects, and sociodemographic factors in patients in the acute phase of stroke: an association analysis

RESUMO Objetivo Analisar a associação da independência funcional com aspectos clínicos de comprometimento neurológico, a localização e extensão do dano neuronal e os fatores sociodemográficos em pacientes na fase aguda do AVC. Método Estudo analítico de recorte transversal, realizado com 90 pacientes adultos e idosos acometidos por AVC isquêmico, que tiveram admissão no ambiente hospitalar nas primeiras 24 horas após o evento vascular. A coleta dos dados referentes aos aspectos clínicos e fatores sociodemográficos foi realizada pelo prontuário eletrônico e/ou entrevista para descrever o perfil dos pacientes, Oxfordshire Community Stroke Project, Alberta Stroke Programme Early CT Score, National Institute of Health Stroke Scale e a Medida de Independência Funcional. Resultados O comprometimento neurológico, de acordo com a National Institute of Health Stroke Scale, foi associado à funcionalidade nas primeiras 24 horas após o AVC. Além disso, a presença de hipertensão arterial, idade, trabalho inativo, tabagismo e extensão do dano neuronal estiveram associados à dependência funcional, mas não permaneceram no modelo final deste estudo. Conclusão A dependência funcional está associada à hipertensão arterial, idade, trabalho inativo, tabagismo, extensão do dano neuronal e grau de comprometimento neurológico nas primeiras 24 horas após o evento vascular. Além disso, um nível mais elevado de comprometimento neurológico foi independentemente associado a níveis aumentados de dependência funcional.

ABSTRACT Purpose To analyze the association of functional independence with clinical aspects of neurological impairment, the location and extent of neuronal damage and sociodemographic factors in patients in the acute phase of stroke. Methods Analytical cross-sectional study in 90 adult and older patients affected by ischemic stroke, admitted to the hospital within 24 hours of the vascular event. Sociodemographic factors and clinical aspects data were collected from electronic medical records and/or interviews in order to depict the patients'profile, Oxfordshire Community Stroke Project, Alberta Stroke Programme Early CT Score, National Institute of Health Stroke Scale, and Functional Independence Measure. Results Neurological impairment, according to the National Institute of Health Stroke Scale, was associated with functioning in the first 24 hours after the stroke. Furthermore, the presence of arterial hypertension, age, inactive work, smoking and extent of neuronal damage were associated with functional dependence, but did not remain in the final model of this study. Conclusion Functional dependence is associated with arterial hypertension, age, inactive work, smoking, extent of neuronal damage, and degree of neurological impairment in the first 24 hours after the vascular event. Furthermore, a higher level of neurological impairment was independently associated with increased levels of functional dependence.

Influence of anxiety/depression on chemotherapy-induced oral mucositis and related quality of life: A prospective cohort study.

OBJECTIVE: The impact of anxiety and depression on chemotherapy-induced oral mucositis has not been extensively explored in the literature. The aim of the present study was to evaluate anxiety/depressive symptoms, health-related quality of life, and oral health-related quality of life and their association with oral mucositis among individuals receiving chemotherapy. METHODS: This is a prospective longitudinal study carried out at a Brazilian referral service. The Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Oral Health Impact Profile questionnaire (OHIP-14) were applied at D0 (before chemotherapy) and D15 of chemotherapy. Clinicodemographic data and oral mucositis severity scores were evaluated. RESULTS: A total of 37 individuals (median age: 49 years) were included in the study. Nearly 38% of patients developed chemotherapy-induced oral mucositis and had higher anxiety/depression scores at baseline. Oral mucositis had a negative impact on oral health-related quality of life regarding functional limitation, physical pain, physical disability, and handicap. CONCLUSION: Anxiety/depressive symptoms are associated with oral mucositis that affects overall health and oral health-related quality of life.

Behavioral or neuropsychiatric symptoms of Alzheimer's disease: from psychopathology to pharmacological management / Sintomas comportamentais ou neuropsiquiátricos da doença de Alzheimer: psicopatologia e abordagem terapêutica

Abstract Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.

Resumo Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto "comprometimento comportamental leve", correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.

Social cognition across bipolar disorder and behavioral-variant frontotemporal dementia: an exploratory study

Objectives: Bipolar disorder type 1 (BD1) and behavioral-variant frontotemporal dementia (bvFTD) share similar behavioral and cognitive symptoms, rendering the differential diagnosis between them a clinical challenge. We investigated the accuracy of social cognition (SC) measures to differentiate bvFTD from BD. Methods: We included three groups of participants: early-onset BD1 (in remission, n=20), bvFTD (n=18), and cognitively healthy controls (HC) (n=40), matched for age, schooling, and sex. All participants underwent cognitive assessment, including the Facial Emotion Recognition (FER) and Modified Faux-Pas (mFP) tests, which assess mentalizing. Results: Compared to HC, BD1 and bvFTD patients underperformed on both SC measures. BD1 and bvFTD did not differ regarding FER or mFP total scores, although patients with bvFTD had significantly higher difficulties than those in the BD1 group to detect social faux-pas (p < 0.001, d = 1.35). Conclusion: BD1 and bvFTD share deficits in the core SC functions. These findings should be considered in the development of tasks aiming to improve clinical differentiation between the two disorders.

Association of anxiety and depression with oral mucositis: A systematic review.

OBJECTIVE: Anxiety and depression are frequent conditions among individuals undergoing antineoplastic therapy, but their relationship with oral mucositis is unclear. This systematic review evaluated the potential association of anxiety and depression with frequency and severity of chemo/radiotherapy-induced oral mucositis. MATERIALS AND METHODS: Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature searches in three other databases. The risk of bias was assessed using the Joanna Briggs Institute tool. RESULTS: Eight observational studies conducted on 954 individuals (male-to-female ratio: 1.1:1; age range: six-82 years). Three (37.5%) studies included patients with solid tumors, two (25%) studies included hematopoietic/lymphoid tissue tumors, and two (25%) studies comprised mixed types of malignant neoplasms. Eight different instruments were used to assess oral mucositis, while seven different instruments were used to evaluate anxiety and depression. Associations of anxiety and/or depression with oral mucositis severity were reported in six (75.0%) studies. Oral mucositis-related symptoms, especially pain, were linked with depression in three (37.5%) studies. CONCLUSION: A relatively low number of cases and data heterogeneity hamper definitive conclusion about the potential association between anxiety/depression and oral mucositis. Further studies that could guide more personalized treatments are warranted to investigate this plausible bidirectional interaction.

Cognitive evaluation in Parkinson's disease: applying the Movement Disorder Society recommendations in a population with a low level of formal education / Avaliação cognitiva na doença de Parkinson: aplicando as recomendações da Movement Disorder Society em uma população de baixa escolaridade

Abstract Background The diagnosis of cognitive disorders in Parkinson disease (PD) can be very challenging. Aiming at establishing uniform and reliable diagnostic procedures, the International Parkinson's Disease and Movement Disorder Society (MDS) commissioned task forces to delineate diagnostic criteria for mild cognitive impairment (MCI) and dementia in PD. Objectives To investigate the applicability of the MDS recommendations for cognitive evaluation in a Brazilian sample of patients with PD with low levels of formal education. Methods A total of 41 patients with PD were subjected to a comprehensive neuropsychological evaluation based on tests proposed by the MDS, which included the Mini-Mental State Examination, the Mattis Dementia Rating Scale (MDRS), the Trail Making Test (TMT) parts A and B, in addition to language and memory skills assessment. Neuropsychiatric and daily functioning features were also evaluated. Spearman correlation analyses were used to evaluate the association between the scores obtained in the cognitive scales and demographic/clinical variables. Results Although none of the participants had a formal diagnosis of dementia, 50% presented some degree of cognitive impairment when considering the results of the MDRS. Of note, a noticeable number of patients was not able to complete the full neuropsychological assessment. The TMT part B was the most difficult task, being completed by only 22 participants (54%). As expected, the greater the educational level, the better the performance on the cognitive tests. Better motor function was also associated with better scores in cognition. Conclusions Adopting strict inclusion/exclusion criteria and a comprehensive clinical evaluation, we found remarkable limitations for the MDS recommendations when individuals with low educational levels are considered. A revision of the current guidelines is necessary considering differences among populations, especially related to formal education.

Resumo Antecedentes O diagnóstico de distúrbios cognitivos na doença de Parkinson (DP) pode ser muito desafiador. Com o objetivo de estabelecer procedimentos diagnósticos uniformes e confiáveis, a Sociedade Internacional da Doença de Parkinson e Distúrbios do Movimento (MDS, na sigla em inglês) encomendou forças-tarefa para delinear critérios diagnósticos para comprometimento cognitivo leve (CCL) e demência na DP. Objetivos Investigar a aplicabilidade das recomendações da MDS para avaliação cognitiva em uma amostra brasileira de pacientes com DP de baixa escolaridade. Métodos Um total de 41 pacientes com DP foram submetidos a uma avaliação neuropsicológica abrangente com base nos testes propostos pela MDS, que incluiu o Miniexame do Estado Mental, a Escala de Avaliação de Demência de Mattis (MDRS, na sigla em inglês), o teste de trilhas (TMT, na sigla em inglês) partes A e B, além da avaliação das habilidades de linguagem e memória. Características neuropsiquiátricas e de funcionamento diário também foram avaliadas. Análises de correlação de Spearman foram utilizadas para avaliar a associação entre os escores obtidos nas escalas cognitivas e variáveis demográficas/clínicas. Resultados Apesar de nenhum dos participantes ter diagnóstico formal de demência, 50% apresentaram algum grau de comprometimento cognitivo ao levar em consideração os resultados da MDRS. Vale ressaltar que um número notável de pacientes não conseguiu completar a avaliação neuropsicológica completa. A parte B do TMT foi a tarefa mais difícil, sendo realizada por apenas 22 participantes (54%). Como esperado, quanto maior o nível educacional, melhor o desempenho nos testes cognitivos. Melhor função motora também foi associada a melhores escores em cognição. Conclusões Adotando critérios rígidos de inclusão/exclusão e uma avaliação clínica abrangente, encontramos limitações marcantes para as recomendações da MDS quando considerados indivíduos com baixa escolaridade. É necessária uma revisão das diretrizes atuais considerando as diferenças entre as populações, principalmente relacionadas ao nível educacional.

Cognitive assessment of Brazilian patients with multiple sclerosis: weighing the impact of disability and depressive symptoms / Avaliação cognitiva de pacientes brasileiros com esclerose múltipla: análise do impacto da incapacidade e dos sintomas depressivos

ABSTRACT Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. Cognition is not routinely assessed in patients with MS though they frequently have cognitive complaints or dysfunction. Objective: The aim of this study was to compare the cognitive status of patients with MS with age, sex, and schooling matched controls and to evaluate the potential influence of clinical parameters on cognition. Methods: A total of 35 patients with MS (mean±SD age 37.9 years±11.44, M/F: 12/23) and 33 healthy controls (mean±SD age 38.8 years±12.6, M/F: 12/21) were enrolled in this study. All subjects underwent a structured clinical assessment and the cognitive tools are as follows: Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Rey Auditory Verbal Learning Test (RAVLT), Digit Span, and Verbal Fluency Tests (letters F, A, and S and animal category). Psychopathology was assessed with the Mini International Neuropsychiatric Interview and the Beck Depression Inventory (BDI). The Expanded Disability Status Scale (EDSS) was used for patients. Results: Patients performed worse than controls in almost all tests, with approximately 70% of patients presenting cognitive impairment. The most affected cognitive domain was episodic memory (45.7%), followed by verbal fluency (42.8%) and information processing speed (22.8%). SDMT was inversely correlated with disease severity, as assessed by the EDSS. Depression did not influence cognitive performance in this cohort. Conclusions: Cognitive dysfunction is common among patients with MS. While motor impairment was associated with information processing speed, depression did not influence cognitive performance.

RESUMO A esclerose múltipla (EM) é a doença desmielinizante mais comum do sistema nervoso central. A cognição não é rotineiramente avaliada nos pacientes apesar da ocorrência frequente de queixas ou disfunção cognitivas. Objetivo: Comparar o perfil de pacientes com EM com controles pareados por idade, sexo e escolaridade e investigar a potencial influência de parâmetros clínicos na cognição. Métodos: Trinta e cinco pacientes com EM (idade média±desvio padrão [DP] 37,9 anos±11,44, H/M: 12/23) e 33 controles saudáveis (idade média±DP 38,8 anos±12,6, H/M: 12/21) foram incluídos neste estudo. Todos os participantes passaram por avaliação clínica estruturada e por testagem cognitiva com os seguintes instrumentos: Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Rey Auditory Verbal Learning Test (RAVLT), Digit Span e testes de fluências verbais (letras F, A e S e categoria-animais). A psicopatologia foi investigada com a Mini International Neuropsychiatric Interview e com o Beck Depression Inventory (BDI). A Expanded Disability Status Scale (EDSS) foi aplicada nos pacientes. Resultados: Pacientes tiveram desempenho pior que os controles na maioria dos testes — 70% deles tiveram déficit cognitivo. A função cognitiva mais frequentemente afetada foi memória episódica (45,7%), seguida por fluência verbal (42,8%) e velocidade de processamento (22,8%). A pontuação no SDMT correlacionou-se inversamente com a gravidade da doença, medida pela EDSS. A depressão não influenciou o desempenho cognitivo nesta série de pacientes. Conclusões: Declínio cognitivo é comum em pacientes com EM. Enquanto o déficit motor se associou com a velocidade de processamento, a depressão não influenciou o desempenho cognitivo.

Modified Levels of Renin Angiotensin Related Components in the Frontal Cortex and Hippocampus were Associated with Neuroinflammation and Lower Neuroprotective Effects of NGF During Acute Hepatic Encephalopathy in Mice.

BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves cognitive and motor dysfunctions due to hepatic failure. The clinical and experimental studies suggest that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R), which compose the classical pathway of the renin-angiotensin system (RAS), exacerbate neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor, which integrate the alternative RAS axis, have been shown as promising therapeutic targets in neuropsychiatric disorders, leading to neuroprotection. OBJECTIVE: This study aimed to investigate the potential participation of the RAS components in thioacetamide (TAA)-induced HE in mice. METHODS: We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF) were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the chemokine (CCL2) were quantified by cytometric bead array. The student's t-test was applied for statistical analysis. RESULTS: Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6, IL-12, and CCL2 in the hippocampus compared with controls. CONCLUSION: This study suggested that the reduction of components of the alternative RAS axis was associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF during TAA-induced HE.

Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia.

This study investigated whether blood-based biomarkers were related to functional test performance and respiratory muscle strength in older adults with COPD and sarcopenia. The participants included in this cross-sectional study were from both sexes and sixty years or older. Based on clinical assessment, participants were categorized in COPD (n = 43) and non-COPD (NCOPD) (n = 43) groups. They were also assessed for body composition and muscular mass by dual-energy X-ray absorptiometry, using the relative skeletal muscle index for the diagnosis of sarcopenia. A series of functional tests, including short physical performance battery (SPPB), 6-minute walking test (6MWT), maximal inspiratory and expiratory pressures (MIP and MEP), were carried out. Plasma levels of myokines (Irisin and BDNF), and soluble TNF receptors (sTNFR1 and sTNFR2) were determined by ELISA. In the multivariate analysis, 6MWD was associated with age, COPD-related sarcopenia and BDNF (R2 = 0.29; f2 = 0.41). SPPB score was associated with COPD-related sarcopenia and sTNFR1 (R2 = 0.25; f2 = 0.33). MIP value was associated with sex, COPD-related sarcopenia, sTNFR2 and Irisin (R2 = 0.24; f2 = 0.31). Finally, MEP value was associated with sex COPD-related sarcopenia (R2 = 0.18; f2 = 0.22). Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia.

Traumatic brain injury in Brazil: an epidemiological study and systematic review of the literature / Traumatismo cranioencefálico no Brasil: um estudo epidemiológico e uma revisão sistemática da literatura

ABSTRACT Background: Traumatic brain injury (TBI) is a serious public health problem worldwide. Although TBI is common in developing countries, there are few epidemiological studies. Objective: To investigate the sociodemographic and clinical features of patients with TBI at the Hospital João XXIII, a public reference center for trauma in Belo Horizonte, Brazil, and to systematically review the available literature on TBI in Brazil. Methods: Clinical and sociodemographic data were collected from electronic medical records for the entire month of July 2016. The literature on epidemiology of TBI in Brazil was systematically reviewed using MeSH/DeCS descriptors in the PubMed and Lilacs databases. Results: Most patients admitted with TBI were male and under 60 years of age. Mild TBI was the most prevalent form and the most common cause of TBI was falls. A Glasgow Coma Scale score below 12, neuroimaging changes on computer tomography, and presence of any medical conditions were significantly associated with longer hospital stay. Brazilian studies showed that TBI affected mainly men and young adults. In addition, mild TBI was the most common TBI severity reported and the most common causes were motor vehicle accidents and falls. Conclusions: Overall, the profile of TBI in this center reflects the data from other Brazilian studies.

RESUMO Antecedentes: O traumatismo cranioencefálico (TCE) representa, mundialmente, um problema sério de saúde pública. Apesar de o TCE ser prevalente em países em desenvolvimento, estudos epidemiológicos permanecem escassos. Objetivo: Investigar as características sociodemográficas e clínicas de pacientes acometidos por TCE no Hospital João XXIII - centro de referência em trauma situado em Belo Horizonte, Brasil - e revisar sistematicamente toda a literatura disponível sobre o TCE no Brasil. Métodos: Os dados clínicos e sociodemográficos foram coletados apenas para o mês de julho, 2016, por meio de prontuários eletrônicos. A literatura sobre a epidemiologia do TCE no Brasil foi sistematicamente revisada usando descritores Medical Subject Headings (MeSH)/Descritores em Ciências da Saúde (DeCS) nos bancos de dados PubMed e Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs). Resultados: Os pacientes acometidos por TCE eram em sua maioria homens com menos de 60 anos. O TCE leve foi a gravidade mais prevalente entre os casos. O TCE foi causado principalmente por quedas. Escores menores que 12 na escala de Coma de Glasgow mais alterações de neuroimagem em tomografia computadorizada e a presença de qualquer comorbidade médica estão significativamente associados à maior estadia hospitalar. Estudos brasileiros demonstraram que o TCE acomete principalmente homens e adultos jovens. Além disso, o TCE leve foi a gravidade mais comum reportada, e os mecanismos de TCE mais comuns foram acidentes automobilísticos e quedas. Conclusões: O perfil de pacientes acometidos por TCE no centro de referência em questão reflete os dados de outros estudos brasileiros.

Adiponectin and Stnfr2 peripheral levels are associated with cardiovascular risk in patients with schizophrenia.

OBJECTIVES: To investigate the association between cytokine peripheral levels and the risk of cardiovascular disease in patients with schizophrenia and controls. METHODS: A sample of 40 patients and 40 control subjects participated in the study. Psychiatric diagnosis was established following structured clinical assessment. The Framingham Score was used to assess cardiovascular risk (CVR). Serum levels of the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were determined by cytometric bead array (CBA) technique, and the serum levels of IL-33, sST2, sTNFR1, sTNFR2, Leptin and Adiponectin by Enzyme-Linked Immunosorbent assay (ELISA). RESULTS: Patients with schizophrenia showed greater frequency of moderate CVR when compared with controls (p = 0.14). In addition, patients showed higher levels of sTNFR2 and Adiponectin compared to controls (p = 0.007 and p < 0.001, respectively). Adiponectin and sTNFR2 were associated with CVR only in patients (p = 0.0002 and p = 0.033, respectively). In multivariate analysis controlling for socio-demographic and clinical confounders, illness duration (r = 0.492; p < 0.002) and sTNFR2 (r = 0.665; p < 0.004) were independent predictors of CVR. CONCLUSION: Our results reinforce the concept that patients with schizophrenia are at greater risk to develop cardiovascular diseases, and suggest that the associated chronic low-grade inflammation might play a role in this process.

Oral mucositis: Current knowledge and future directions.

Oral mucositis secondary to head and neck chemoradiation displays a complex molecular pathogenesis involving epithelial and microvascular injury, release of pro-inflammatory cytokines, and host-microbiome communications. These processes lead to oxidative stress and the release of reactive oxygen species that stifle the structural integrity of the oral mucosa, with emergence of erosions and ulcers. The consequences are malnutrition, psychological/psychiatric symptoms, poor quality of life, and occurrence of opportunistic infections. The latter pose a major challenge due to the risk of interruption of anti-neoplastic therapy, tumour recurrence and, ultimately, death. This article aims to present the clinical characteristics, molecular pathogenesis, and an overview of the predisposing factors and current management of oral mucositis. It is anticipated that the future direction of the management of oral mucositis will focus on evidence-based prehabilitation and pre- and per-chemoradiation therapy monitoring.

Transtorno Depressivo Maior: Um Estudo Comparativo sobre Cognição Socioemocional e Funções Executivas / Major Depressive Disorder: A Comparative Study on Socio-Emotional Cognition and Executive Functions

Resumo O objetivo deste estudo foi avaliar a cognição socioemocional e as funções executivas em pacientes com Transtorno Depressivo Maior unipolar. A amostra incluiu 22 pacientes entre 36 e 93 anos de idade (M = 59,32; DP = 12,89) e 23 indivíduos controles entre 30 e 81 anos de idade (M = 63,00; DP = 13,56). Além de dados demográficos, foram avaliados sintomas de ansiedade e de depressão, empatia, teoria da mente, reconhecimento de emoções, controle inibitório, flexibilidade cognitiva e fluência verbal. Não houve diferença estatística significativa entre os grupos quanto à idade e à escolaridade. Os pacientes apresentaram significativamente mais ansiedade, depressão e angústia pessoal do que os controles. Indivíduos com sintomas depressivos mais graves apresentaram menor velocidade de processamento.

Abstract The present study aimed to assess socioemotional cognition and executive functions in patients with unipolar Major Depressive Disorder. The sample included 22 patients between 36 and 93 years of age (M = 59.32; SD = 12.89) and 23 patients between 30 and 81 years of age (M = 63.00; SD = 13.56) controls. In addition to demographic data, symptoms of anxiety and depression, empathy, theory of mind, recognition of emotions, inhibitory control, cognitive flexibility and phonemic verbal fluency were obtained. There was no statistical difference between the groups regarding age and education. Patients had significantly more anxiety, depression and personal distress than controls. Individuals with more severe depressive symptoms had a lower processing speed than the others.

Stroke in Chagas disease: from pathophysiology to clinical practice

ABSTRACT Despite substantial progress toward its control, Chagas disease continues to be a major public health problem in Latin America and has become a global health concern. The disease affects approximately 6 million people, of whom 20-40% will develop cardiomyopathy over the years after the initial Trypanosoma cruzi infection. Chagas cardiomyopathy is the most serious and frequent manifestation of Chagas disease. Clinical manifestations vary widely according to the severity of myocardial dysfunction, ranging from asymptomatic to severe forms, including dilated cardiomyopathy with heart failure, arrhythmias, thromboembolism events, and sudden death. Chagas disease is a risk factor for stroke regardless of the severity of cardiomyopathy, which is a leading cause of chronic disability. Classically, stroke etiology in patients with Chagas disease is thought to be cardioembolic and related to apical aneurysm, mural thrombus, and atrial arrhythmias. Although most strokes are thromboembolic, other etiologies have been observed. Small vessel disease, atherosclerosis, and cryptogenic diseases have been reported in patients with Chagas disease and stroke. The potential mechanisms involved in non-embolic strokes include the presence of associated risk factors, pro-inflammatory and prothrombotic disease states, and endothelial dysfunction. However, the contribution of each mechanism to stroke in Chagas disease remains unclear. The review aims to provide an overview of stroke in Chagas disease, highlighting the main pathophysiological mechanisms, clinical presentation, approaches for prevention, and unanswered questions regarding treatment strategies.

IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Role of cytokine and neurotrophic factors in nicotine addiction in the conditioned place preference paradigm.

The mechanisms involved in the maintenance of cigarette smoking and nicotine reward remain unclear. Immune response might play an important role in this context. Nicotine may induce both central and systemic inflammatory responses as well as changes in the regulation of brain-derived neurotrophic factor (BDNF). The conditioned place preference (CPP) is a method used for the evaluation of nicotine-induced reward, reproducing nicotine-seeking behavior in humans. So far, there are no studies investigating the relationship between neuroinflammation and nicotine-induced CPP. This study aimed to evaluate the levels of inflammatory mediators and neurotrophic factors in key areas of the central nervous system (CNS) of mice subject to nicotine-induced CPP. CPP was induced with an intraperitoneal administration of 0.5 mg/kg of nicotine in male Swiss mice, using an unbiased protocol. Control group received vehicle by the same route. The levels of cytokines, chemokines, and neurotrophic factors were measured using Enzyme-Linked Immunosorbent Assay (ELISA) in the brain after CPP test. As expected, nicotine induced place preference behavior. In parallel, we observed increased peripheral levels of IL-6 and IL-10 alongside increased hippocampal levels of NGF but decreased GDNF in mice treated with nicotine compared to controls. In the striatum, nicotine promoted decrease of IL-1ß, IL-10 and GDNF levels, while the levels of all the mediators were similar between groups in the pre-frontal cortex. Our results provide evidence on the role of cytokines and neurotrophic factors in nicotine-induced CPP in mice.

Inflammatory Markers Profile in Older Adolescents During Treatment with Selective Serotonin Reuptake Inhibitors.

Objective: This study aimed to investigate the serum levels of inflammatory markers in adolescents with major depressive disorder (MDD) using selective serotonin reuptake inhibitors. Methods: This was an 8-month observational study, involving 30 adolescents with and 38 without (control) MDD diagnosis. Demographic (age and gender) and anthropometric data (weight, height, and calculated body mass index [BMI] z score) were collected. Body composition was assessed with whole-body DXA scan. Depressive and anxiety symptoms were assessed using the Beck Depression and Anxiety Inventories (BDI-II and BAI), respectively. Serum levels of interleukin (IL)-6, IL-8, IL-1ß, tumor necrosis factor, monocyte chemoattractant protein-1 (MCP-1), leptin, resistin, and adiponectin were measured using Bio-Plex Multiplex Immunoassays at baseline and after 8 months. Results: At baseline, patients with MDD and controls did not differ in age, gender, BMI z score, and fat mass index (FMI) z score. At follow-up, 58.3% (21/36) of patients with MDD were in full remission. Patients with MDD had higher levels of resistin at baseline (26274.16 pg/mL [16162.68-54252.72]) than controls (21678.53 pg/mL [11221.17-37343.27]; p < 0.01). This difference remained statistically significant after adjustment for sex, age, and FMI z score. No differences in other inflammatory markers were observed between the groups. By follow up, depressive and anxiety symptom severity had decreased significantly in patients with MDD in parallel with a decrease in the serum levels of TNF (p = 0.02), IL-8 (p < 0.01) and MCP-1 (p = 0.04). Among these markers, BDI-II score was positively correlated with serum levels of MCP-1. Conclusion: These results corroborate the view of involvement of peripheral inflammatory mechanisms in the pathophysiology of MDD in adolescents. This trial is registered at ClinicalTrials.gov: NCT02147184.

Low-dose candesartan prevents schizophrenia-like behavioral alterations in a neurodevelopmental two-hit model of schizophrenia.

Schizophrenia is a severe mental disorder with complex etiopathogenesis. Based on its neurodevelopmental features, an animal model induced by "two-hit" based on perinatal immune activation followed by peripubertal unpredictable stress was proposed. Sex influences the immune response, and concerning schizophrenia, it impacts the age of onset and symptoms severity. The neurobiological mechanisms underlying the influence of sex in schizophrenia is poorly understood. Our study aimed to evaluate sex influence on proinflammatory and oxidant alterations in male and female mice exposed to the two-hit model of schizophrenia, and its prevention by candesartan, an angiotensin II type 1 receptor (AT1R) blocker with neuroprotective properties. The two-hit model induced schizophrenia-like behavioral changes in animals of both sexes. Hippocampal microglial activation alongside the increased expression of NF-κB, and proinflammatory cytokines, namely interleukin (IL)-1ß and TNF-α, were observed in male animals. Conversely, females presented increased hippocampal and plasma levels of nitrite and plasma lipid peroxidation. Peripubertal administration of low-dose candesartan (0.3 mg/kg PO) prevented behavioral, hippocampal, and systemic changes in male and female mice. While these results indicate the influence of sex on inflammatory and oxidative changes induced by the two-hit model, candesartan was effective in both males and females. The present study advances the neurobiological mechanisms underlying sex influence in schizophrenia and opens new avenues to prevent this devasting mental disorder.