Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil.

Atherosclerotic Cardiovascular Disease (ASCVD) represents the leading cause of death worldwide, and individual screening should be based on behavioral, metabolic, and genetic profile derived from data collected in large population-based studies. Due to the polygenic nature of ASCVD, we aimed to assess the association of genomics with ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events at population level. CardioVascular Genes (CV-GENES) is a nationwide, multicenter, 1:1 case-control study of 3,734 patients in Brazil. Inclusion criterion for cases is the first occurrence of one of the ASCVD events. Individuals without known ASCVD will be eligible as controls. A core lab will perform the genetic analyses through low-pass whole genome sequencing and whole exome sequencing. In order to estimate the independent association between genetic polymorphisms and ASCVD, a polygenic risk score (PRS) will be built through a hybrid approach including effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the PRS, and number of non-missing SNPs in the sample. In addition, the presence of pathogenic or likely pathogenic variants will be screened in 8 genes (ABCG5, ABCG8, APOB, APOE, LDLR, LDLRAP1, LIPA, PCSK9) associated with atherosclerosis. Multiple logistic regression will be applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), and population attributable risks will be calculated. Clinical trial registration: This study is registered in clinicaltrials.gov (NCT05515653).

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19.

Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls. Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI). Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.

Burnout syndrome in nursing residents in COVID-19 pandemic / Burnout syndrome in nursing residents in COVID-19 pandemic

Introduction: The incidence of Burnout Syndrome (BS) among nurses is higher. For this group, nursing residents undergo periodic assessments regarding compliance with the care workload in closed sectors, such as Intensive Care and Emergency Care, that put them at higher risk for the syndrome. Objective: Identify the prevalence and related factors for BS in nursing residents. Material and Methods: Quantitative, analytical, cross-sectional study with 106 nurses enrolled in the Residency program in Rio de Janeiro, Brazil, based on the following instruments: Maslach Burnout Inventory-General Survey Scale and an occupational sociodemographic questionnaire. Non-parametric statistical tests for independent samples were applied and Mann-Whitney test 15 was used for quantitative variables. Results: The results show that variable changes in relationships indicates stage 4 of the BS when compared to the other stages. For the other variables, there were no statistically significant differences. Discussion: Studies reveal that work-family balance is closely related to how job satisfaction is affected and mitigates the negative effects of BS. Conclusions: Consequences on relation patterns are among the most affected symptoms in the lives of nursing residents. This study is expected to contribute to raising awareness of the problem in question and to improve the quality of work life of resident nurses, detecting and preventing their illness.

Introducción: La incidencia del síndrome de burnout en profesionales de enfermería es mayor. Los residentes de enfermería se someten a evaluaciones periódicas sobre el cumplimiento de la carga de trabajo asistencial en servicios cerrados, como unidades de cuidados intensivos y urgencias, que les exponen a un mayor riesgo de padecer este síndrome. Objetivo: Identificar la prevalencia y factores relacionados del síndrome de burnout en residentes de enfermería. Materiales y métodos: Estudio cuantitativo, analítico y transversal que incluyó 106 enfermeros residentes matriculados en el programa de residencia en Río de Janeiro, Brasil, y empleó el Inventario de Burnout de Maslach - Encuesta General y un cuestionario sociodemográfico y ocupacional. Se aplicaron pruebas estadísticas no paramétricas para muestras independientes y se utilizó la prueba de Mann-Whitney para las variables cuantitativas. Resultados: Los resultados muestran que la variable "cambios en las relaciones" se encuentra en etapa 4 del síndrome de burnout en comparación con las demás etapas. En cuanto a las demás variables, no hubo diferencias estadísticamente significativas. Discusión: Los estudios revelan que el equilibrio trabajo-familia está estrechamente relacionado con el modo en que se ve afectada la satisfacción laboral y mitiga los efectos negativos del síndrome de burnout. Conclusiones: Las consecuencias en los patrones de relación se encuentran entre los síntomas más afectados en la vida de los residentes de enfermería. Se espera que este estudio contribuya a concientizar sobre el problema en cuestión y a mejorar la calidad de vida laboral de las enfermeras residentes, detectando y previniendo esta enfermedad.

Introdução: A incidência da Síndrome de Burnout (SB) entre os enfermeiros é maior. Para esse grupo, os residentes de enfermagem são submetidos a avaliações periódicas quanto ao cumprimento da carga horária de cuidados em setores fechados, como Terapia Intensiva e Emergência, o que os coloca em maior risco para a síndrome. Objetivo: Identificar a prevalência e os fatores relacionados à SB em residentes de enfermagem. Material e métodos: Estudo quantitativo, analítico, transversal com 106 enfermeiros matriculados no programa de Residência no Rio de Janeiro, Brasil, com base nos seguintes instrumentos: Maslach Burnout Inventory-General Survey Scale e um questionário sociodemográfico ocupacional. Foram aplicados testes estatísticos não paramétricos para amostras independentes e o teste de Mann-Whitney 15 foi usado para variáveis quantitativas. Resultados: Os resultados mostram que as mudanças variáveis nos relacionamentos indicam o estágio 4 do BS quando comparado com os outros estágios. Para as outras variáveis, não houve diferenças estatisticamente significativas. Discussão: Estudos revelam que o equilíbrio entre trabalho e família está intimamente relacionado à forma como a satisfação no trabalho é afetada e atenua os efeitos negativos da SB. Conclusões: As consequências nos padrões de relacionamento estão entre os sintomas mais afetados na vida dos residentes de enfermagem. Espera-se que este estudo contribua para aumentar a conscientização sobre o problema em questão e para melhorar a qualidade de vida profissional dos enfermeiros residentes, detectando e prevenindo suas doenças.

Desenvolvimento e validação de material instrucional sobre autocuidado em saúde para profissionais atuantes em projetos sociais / Development and validation of instructional material on health self-care for professionals working in social projects / Desarrollo y validación de material didáctico sobre autocuidado de la salud para profesionales que trabajan en proyectos sociales

Objetivo: realizar a validação de conteúdo e de aparência de um e-book sobre autocuidado relacionado à saúde, voltado para profissionais que atuam em projetos sociais. Método: estudo metodológico de validação de conteúdo e de aparência. Para desenvolvimento do material, uma revisão de literatura foi realizada. Participaram 10 juízes especialistas atuantes em um projeto social. Foram considerados válidos os resultados cujo Índice de Validade foi igual ou maior que 0,8. Resultados: o e-book foi dividido em quatro dimensões compostas por um conjunto de cuidados e por sugestões de atividades recreativas a serem desenvolvidas junto aos participantes: 1. física; 2. mental; 3. emocional; e 4. social. A estratégia de Ativação da Intenção foi descrita para apoiar a mudança de comportamento. Conclusão:o e-book inova na articulação entre o autocuidado e a saúde, caracterizando-se como tecnologia potencializadora do desenvolvimento de ações intersetoriais. A sua validação contribui para a aplicabilidade do material

Objective: to perform content and appearance validation of an e-book on health-related self-care, aimed at professionals who work in social projects. Method: methodological study of content and appearance validation. For the development of the material, a literature review was performed. Ten expert judges, working in a social project, participated. Results whose Validity Index was equal or greater than 0.8 were considered valid. Results: The e-book was divided into four dimensions composed of a set of care and recreational activity suggestions to be developed with the participants: 1. physical; 2. mental; 3. emotional; and 4. social. The Intention Activation strategy was described to support behavior change. Conclusion: The e-book innovates in the articulation between self-care and health, being characterized as a potentializing technology for the development of intersectoral actions. Its validation contributes to the applicability of the material

Objetivo: realizar la validación del contenido y de la apariencia de un libro electrónico sobre autocuidado relacionado con la salud, dirigido a profesionales que trabajan en proyectos sociales. Método: estudio metodológico de validación del contenido y de la apariencia. Para el desarrollo del material, se realizó una revisión de la literatura. Participaron 10 jueces especialistas. Se consideraron válidos los resultados cuyo Índice de Validez era igual o superior a 0,8. Resultados: el libro electrónico se dividió en cuatro dimensiones compuestas por un conjunto de cuidados y sugerencias de actividades recreativas a desarrollar con los participantes: 1. física; 2. mental; 3. emocional; 4. social. Se describió la estrategia de activación de la intención para apoyar el cambio de comportamiento. Conclusión: el libro electrónico innova en la articulación entre el autocuidado y la salud, caracterizándose como una tecnología para el desarrollo de acciones intersectoriales. Su validación contribuye a la aplicabilidad del material

Perfil clínico-epidemiológico de queimaduras químicas em uma Unidade de Terapia de Queimados no Brasil / Clinical-epidemiological profile of chemical burns in a Burn Therapy Unit (BTU) in Brazil

Introdução: Substâncias químicas apresentam uma prevalência relativamente baixa dentre as causas de queimaduras. Porém, têm importância, pois a maioria dos acidentes ocorrem no âmbito do trabalho e em população economicamente ativa. O objetivo é realizar uma análise do perfil dos pacientes internados por queimaduras químicas em uma Unidade de Queimados. Métodos: Análise retrospectiva de pacientes internados na Unidade de Queimados do Hospital Estadual de Bauru, Bauru, SP, Brasil, entre os anos de 2008 e 2018. Múltiplas variáveis foram analisadas, como idade, sexo, agente químico, local onde ocorreu o acidente, necessidade de internação em UTI e dias de hospitalização. Resultados: No total, 40 (1,7%) pacientes foram internados devido a queimadura química. A média de idade foi de 35 anos, com predominância do sexo masculino, com 30 (75%) indivíduos. O principal local do trauma foi no ambiente de trabalho, em 20 casos (50%). Acidentes com base foram responsáveis por 20 (50%) internações. A superfície corporal queimada média foi de 7,5%. Queimadura ocular ocorreu em 11 (27,5%) pacientes. Leito de terapia intensiva foi necessário para 10 (25%) casos. Quando comparados os acidentes entre substâncias ácidas e bases, evidenciamos diferença no número de pacientes internados em UTI, com oito pacientes em lesões envolvendo bases e dois com ácidos (p=0,04). Conclusão: A casuística e resultados apresentados neste artigo são semelhantes à literatura mundial sobre o assunto. Evidenciamos a importância dessa queimadura no ambiente de trabalho e o acometimento de indivíduos em idade ativa, assim como a maior gravidade de acidentes com substância química.

Introduction: Chemicals have a relatively low prevalence among the causes of burns. However, they are important because most accidents occur in the scope of work and in an economically active population. The objective is to perform an analysis of the profile of patients hospitalized for chemical burns in a Burn Unit. Methods: Retrospective analysis of patients hospitalized in the Burn Unit of the State Hospital of Bauru, Bauru, SP, Brazil, between 2008 and 2018. Multiple variables were analyzed, such as age, gender, chemical agent, place where the accident occurred, need for ICU stay and days of hospitalization. Results: In total, 40 (1.7%) patients were hospitalized due to chemical burn. The mean age was 35 years, with predominance of males, with 30 (75%) individuals. The main site of trauma was in the workplace, in 20 cases (50%). Based accidents were responsible for 20 (50%) admissions. The mean burned body surface was 7.5%. Eye burn occurred in 11 (27.5%) patients. Intensive care bed was required for 10 (25%) cases. When comparing accidents between acid iced substances and bases, we noted a difference in the number of ICU patients, with eight patients in lesions involving bases and two with acids (p=0.04). Conclusion: The sample and results presented in this article are similar to the world literature on the subject. We evidenced the importance of this burn in the work environment and the involvement of individuals of active age, as well as the greater severity of accidents with chemical substance.

Gene expression profile suggests different mechanisms underlying sporadic and familial mesial temporal lobe epilepsy.

Most patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) have hippocampal sclerosis on the postoperative histopathological examination. Although most patients with MTLE do not refer to a family history of the disease, familial forms of MTLE have been reported. We studied surgical specimens from patients with MTLE who had epilepsy surgery for medically intractable seizures. We assessed and compared gene expression profiles of the tissue lesion found in patients with familial MTLE (n = 3) and sporadic MTLE (n = 5). In addition, we used data from control hippocampi obtained from a public database (n = 7). We obtained expression profiles using the Human Genome U133 Plus 2.0 (Affymetrix) microarray platform. Overall, the molecular profile identified in familial MTLE differed from that in sporadic MTLE. In the tissue of patients with familial MTLE, we found an over-representation of the biological pathways related to protein response, mRNA processing, and synaptic plasticity and function. In sporadic MTLE, the gene expression profile suggests that the inflammatory response is highly activated. In addition, we found enrichment of gene sets involved in inflammatory cytokines and mediators and chemokine receptor pathways in both groups. However, in sporadic MTLE, we also found enrichment of epidermal growth factor signaling, prostaglandin synthesis and regulation, and microglia pathogen phagocytosis pathways. Furthermore, based on the gene expression signatures, we identified different potential compounds to treat patients with familial and sporadic MTLE. To our knowledge, this is the first study assessing the mRNA profile in surgical tissue obtained from patients with familial MTLE and comparing it with sporadic MTLE. Our results clearly show that, despite phenotypic similarities, both forms of MTLE present distinct molecular signatures, thus suggesting different underlying molecular mechanisms that may require distinct therapeutic approaches.

Bioactive compounds with antifungal activity against pathogens isolated from pregnant woman: Gallesia integrifolia (garlic wood) is a promising treatment for vulvovaginal candidiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves, bark, and roots of Gallesia integrifolia are consumed in folk medicine through infusion, decoction, and topical preparation by crushing because of its pharmacological properties in several peripheral system disorders, including microbial infections. The presence of various molecules in different parts of the plant likely confers this species' fungicidal action, but scientific evidence is lacking. Vulvovaginal candidiasis mainly affects women of reproductive age. When left untreated, it can cause pregnancy complications. Currently available antifungals often cause undesirable side effects. New alternative therapeutic strategies based on medicinal plants have been proposed. AIM: To investigate the antifungal activity of G. integrifolia against vulvovaginal candidiasis secretion in pregnant women. MATERIALS AND METHODS: Antifungal activity was determined by the minimum inhibitory concentration (MIC), determined by broth microdilution method using Candida spp (NEWP1210), C. albicans (CCCD-CC001), C. tropicalis (CCCD-CC002) standard and clinical isolates from pregnant women with vulvovaginal candidiasis. Nystatin and fluconazole were used as positive controls. The chemical composition of essential oils that were extracted from leaves, flowers, and fruits of G. integrifolia was determined by gas chromatography coupled to mass spectrometry. Reverse docking was used to suggest a possible target in Candida. Conventional docking was used to identify the most probable compound that inhibits fungal growth. RESULTS: A total of 24 compounds were identified, accounting for ∼99% of volatile constituents in the essential oils. Leaves of G. integrifolia contained 3,5-dithiahexanol-5,5-dioxide (40.93%), flowers contained methionine ethyl ester (46.78%), and fruits contained 2,8-dithianonane (54.01%) as the most abundant compounds. The MICs of essential oils of leaves, flowers, and fruits of G. integrifolia against standard strains of Candida spp, C. albicans, and C. tropicalis ranged from 13.01 to 625.00 µg/mL. The essential oil of flowers more effectively inhibited Candida spp. Essential oils of leaves and flowers were similar to fluconazole against C. albicans. Essential oils of flowers and fruits were similar to fluconazole against C. tropocalis. In Candida yeast species that were isolated from vaginal secretion samples from pregnant patients, the MICs of leaves and flowers ranged from 52.08 to 5000.00 µg/mL. The essential oil of leaves (277.77 µg/mL) was the most active against C. albicans. No significant differences were found between the essential oils of leaves and flowers against C. glabrata. Docking simulations suggested that phytol in leaves and flowers was responsible for the antimicrobial effect. CONCLUSION: The present results suggest the potential therapeutic use of G. integrifolia, especially its leaves and flowers, against Candida and vulvovaginal candidiasis.

Análise clínico-epidemiológica de pacientes HIV positivos internados em uma Unidade de Terapia de Queimados / Clinical-epidemiological analysis of HIV positive patients hospitalized in a Burn Therapy Unit

Introdução: A infecção pelo HIV e as queimaduras são um problema comum de saúde pública, principalmente em países de baixa e média renda. Há uma escassez na literatura sobre a epidemiologia de pacientes HIV positivos hospitalizados em unidades de queimados. O objetivo deste estudo é avaliar dados clínicoepidemiológicos de pacientes HIV positivos internados em uma Unidade de Terapia de Queimaduras. Métodos: Realizada análise retrospectiva de pacientes com diagnóstico de HIV internados na Unidade de Terapia de Queimados do Hospital Estadual de Bauru entre os anos de 2008 e 2018. Resultados: No total, foram revisados 2364 prontuários e encontrados 14 (0,6%) pacientes com diagnóstico de HIV. A idade média foi 43,1 anos. Quanto ao gênero, nove (64,3%) eram masculinos e cinco (35,7%) femininos. O mecanismo mais comum foi por chama direta em 11 (78,7%) casos. A etiologia foi álcool (42,9%) em seis pacientes, em três explosão (21,5%) e os demais foram gasolina, cigarro e contato com escapamento, todos com um (7,1%) caso. A causa mais comum foi acidente, em nove (64,3%) casos, dois (14,3%) tentativa de homicídio, um (7,1%) autoextermínio e dois (14,3%) casos sem informação. Em relação à superfície corporal queimada (%SCQ), cinco (37,5%) apresentavam queimaduras de 0-10%, três (21,4%) de 11-20% e cinco (35,7%) maiores que 20%, e em um era desconhecida. Quatro (28,6%) apresentaram lesões de vias aéreas. Dois (14,3%) pacientes foram a óbito. Conclusão: A prevalência de pacientes HIV positivos queimados internados em uma unidade especializada para este tratamento se assemelha à nacional, com características semelhantes em relação a idade e gênero.

Introduction: HIV infection and burns are common public health issues, especially in low- and middle-income countries. There is a paucity in the literature evaluating the epidemiology of burns hospitalization in HIV patients. This study aims to evaluate the clinical and epidemiological profile of HIV-positive patients hospitalized in a Burn Therapy Unit. Methods: A retrospective analysis of burn patients diagnosed with HIV was performed at the Therapy Unit of the State Hospital of Bauru between 2008 and 2018. Results: 2,364 medical records were reviewed, and 14 (0.6%) patients were diagnosed with HIV. The mean age was 43.1 years. Regarding gender, nine (64.3%) were male, and five (35.7%) were female. The most common mechanism was direct flame in 11 (78.7%) cases. The etiology was alcohol (42.9%) in six patients, in three explosions (21. 5%), and the others were gasoline, cigarettes and contact with exhaustion, all with one (7.1%) case. When the cause of these burns was evaluated, nine (64.3%) were due to accidents, either at work or home, two (14.3%) for attempted murder, one (7.1%) self-extermination, and two (14.3%) cases had no information. Regarding total burn surface area, five (37.5%) had burns of 0-10%, three (21.4%) 11-20% and five (35.7%) greater than 20%, and one was unknown. Four (28.6%) showed airway lesions. Two (14.3%) patients died. Conclusion: The prevalence of burned HIV-positive patients admitted to a specialized unit for this treatment is like the national one, with similar characteristics concerning age and gender.

Benchmarking the proteomic profile of animal models of mesial temporal epilepsy.

OBJECTIVES: We compared the proteomic signatures of the hippocampal lesion induced in three different animal models of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS): the systemic pilocarpine model (PILO), the intracerebroventricular kainic acid model (KA), and the perforant pathway stimulation model (PPS). METHODS: We used shotgun proteomics to analyze the proteomes and find enriched biological pathways of the dorsal and ventral dentate gyrus (DG) isolated from the hippocampi of the three animal models. We also compared the proteomes obtained in the animal models to that from the DG of patients with pharmacoresistant MTLE+HS. RESULTS: We found that each animal model presents specific profiles of proteomic changes. The PILO model showed responses predominantly related to neuronal excitatory imbalance. The KA model revealed alterations mainly in synaptic activity. The PPS model displayed abnormalities in metabolism and oxidative stress. We also identified common biological pathways enriched in all three models, such as inflammation and immune response, which were also observed in tissue from patients. However, none of the models could recapitulate the profile of molecular changes observed in tissue from patients. SIGNIFICANCE: Our results indicate that each model has its own set of biological responses leading to epilepsy. Thus, it seems that only using a combination of the three models may one replicate more closely the mechanisms underlying MTLE+HS as seen in patients.

New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19.

We report on nine patients (eight cases of MS and one case of NMOSD) who presented a disease relapse in close temporal association with their first AZD1222 vaccination dose against COVID-19. These patients had been stable for a median period of six years, with no evidence of disease activity and no change in their medication. After a median of 13 days (7 to 25 days) from vaccination, they developed a new relapse with increased disability and new lesions on magnetic resonance imaging. Although this association may be rare, it might be an adverse event of AZD1222.

Junctional instability in neuroepithelium and network hyperexcitability in a focal cortical dysplasia human model.

Focal cortical dysplasia is a highly epileptogenic cortical malformation with few treatment options. Here, we generated human cortical organoids from patients with focal cortical dysplasia type II. Using this human model, we mimicked some focal cortical dysplasia hallmarks, such as impaired cell proliferation, the presence of dysmorphic neurons and balloon cells, and neuronal network hyperexcitability. Furthermore, we observed alterations in the adherens junctions zonula occludens-1 and partitioning defective 3, reduced polarization of the actin cytoskeleton, and fewer synaptic puncta. Focal cortical dysplasia cortical organoids showed downregulation of the small GTPase RHOA, a finding that was confirmed in brain tissue resected from these patients. Functionally, both spontaneous and optogenetically-evoked electrical activity revealed hyperexcitability and enhanced network connectivity in focal cortical dysplasia organoids. Taken together, our findings suggest a ventricular zone instability in tissue cohesion of neuroepithelial cells, leading to a maturational arrest of progenitors or newborn neurons, which may predispose to cellular and functional immaturity and compromise the formation of neural networks in focal cortical dysplasia.

Epidemiology of Burn-Related Morbidity and Mortality in Patients Over 80 Years of Age.

Burns cause greater morbidity and mortality in older patients owing to the physiological changes and functional status declines with age. We sought to characterize the epidemiology of burn injuries in the patient population aged over 80 years. A retrospective analysis of all patients aged >80 years admitted to a tertiary burn center in Brazil over a 10-year period was conducted. Multiple parameters including comorbidities, BSA burned, intensive care unit (ICU) admissions, inhalation injury, and revised Baux score were analyzed to assess association with mortality. Twenty-six patients were identified. The overall mortality rate was 42.3%. The mortality rate increased with the TBSA, with 100% mortality at >20% total BSA involvement (P < .001). Inhalation injury occurred in 3 (11.5%) patients, all of whom suffered mortality (P < .001). ICU admission was necessary for 14 (53.8%) patients, out of which 11 (78.6%) did not survive (P < .001). The revised Baux score had a significant impact on the mortality, with higher values among patients who did not survive (89.2 ± 6.2 vs 110.7 ± 17.9, P < .001). Burns cause high mortality in the octogenarian and nonagenarian populations. It is important to stratify patients at high risk, institute prompt treatment and discuss goals of care early on for optimal patient outcomes.

Erosive Effect of Analgesics on Primary Tooth Enamel - An in Vitro Study

Abstract Objective: To evaluate in vitro erosive effect of analgesics on primary tooth enamel. Material and Methods: The pH and the titratable acidity measurements of the medicines were performed in triplicate using a digital pH meter. Enamel slabs of primary teeth flat and polished were selected by initial surface microhardness analysis. Medications were selected and specimens were assigned into five groups (n=12): Dalsy; Magnopyrol; Paracetamol; Tylenol; and distilled water (negative control). Specimens were immersed in 5 ml of each group solution for 30 min, 4x/day for three days and stored in artificial saliva at 37 °C between immersions and at night. Final microhardness was determined. The data were submitted to Oneway ANOVA and Tukey's test. Scanning electron microscopy (SEM) analysis was performed in three specimens of each group. Results: Medicines showed acidic pH and mean values of titratable acidity ranged from 1.46 to 11.66 ml of 0.1N NaOH. The mineral loss of Magnopyrol was statistically significant in relation to the control group (p<0.01). Magnopyrol showed higher values when compared to Tylenol (p<0.05). SEM images displayed microstructure alterations in the Paracetamol group. Conclusion: Despite the low pH values, only Magnopyrol showed greater enamel softening. Paracetamol demonstrated morphological changes in primary tooth enamel (AU).

A vivência do pai no nascimento por cesariana no centro obstétrico: contribuições para a assistência / The father's experience in cesarean birth at the obstetric center: contributions to care / La experiencia del padre al nacimento por cesárea en el centro obstétrico: contribuciones a la asistencia

Objective: the study's goal has been to describe the experience of the accompanying father in the birth process by caesarean section at the Obstetric Center and point out the favorable and unfavorable conditions that influence this process.Methods: qualitative research, carried out at a University Hospital from august to september 2016 with 10 accompanying parents. The data collection was established by a semi-structured interview, submitted to Bardin's content analysis. Results: through the analysis, two categories emerged: possibilities and limitations in the experience of accompanying parents and emotional aspects in the birth process, which include the physical aspects of the operating room, the welcoming and guidance of the multidisciplinary team and the feelings presented by the parents. Conclusion: the father's participation in the cesarean delivery provides positive impacts for the mother-child-family trinomial, making crucial his presence since prenatal care and the physical adequacy of the cesarean environment

Objetivo: descrever a vivência do pai acompanhante no processo de nascimento por cesariana no Centro Obstétrico e apontar as condições favoráveis e desfavoráveis que influenciaram neste processo. Métodos: pesquisa qualitativa, realizada em um Hospital Universitário de agosto a setembro de 2016 com 10 pais acompanhantes. A coleta de dados se estabeleceu por meio de uma entrevista semiestruturada, submetida à análise de conteúdo de Bardin. Resultados: pela análise, emergiram duas categorias: possibilidades e limitações na vivência do pai acompanhante e aspectos emocionais no processo de nascimento, que compreenderam: os aspectos físicos da sala de cirurgia, o acolhimento e orientação da equipe multiprofissional e os sentimentos apresentados pelos pais. Conclusão: a participação do pai no parto cesárea proporciona impactos positivos ao trinômio mãe-filho-família, tornando cruciais a sua presença desde o pré-natal e a adequação física do ambiente da cesárea

Objetivo: describir la experiencia del padre acompañante en el proceso de parto por cesárea en el Centro de Obstetricia y señalar las condiciones favorables y desfavorables que influyeron en este proceso. Métodos: investigación cualitativa realizada en un Hospital Universitario de agosto a septiembre de 2016 con 10 padres acompañantes. La recopilación de datos se estableció mediante una entrevista semiestructurada, sometida al análisis del contenido de Bardin. Resultados: por análisis, surgieron dos categorías: posibilidades y limitaciones en la experiencia del padre acompañante y aspectos emocionales en el proceso del parto, que incluyeron los aspectos físicos de la sala de operaciones, la bienvenida y la orientación del equipo multidisciplinario y los sentimientos presentados por los padres. Conclusión: la participación del padre en la cesárea proporciona impactos positivos para el trinomio madre-hijo-familia, lo que hace que su presencia desde la atención prenatal y la adecuación física del entorno de la cesárea sean cruciales

International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax  = -0.20, dmin  = -0.09). The bilateral putamen (dleft  = -0.14, dright  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial.

OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. METHODS: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. RESULTS: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. SIGNIFICANCE: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future.

Exploring a Region on Chromosome 8p23.1 Displaying Positive Selection Signals in Brazilian Admixed Populations: Additional Insights Into Predisposition to Obesity and Related Disorders.

We recently reported a deviation of local ancestry on the chromosome (ch) 8p23.1, which led to positive selection signals in a Brazilian population sample. The deviation suggested that the genetic variability of candidate genes located on ch 8p23.1 may have been evolutionarily advantageous in the early stages of the admixture process. In the present work, we aim to extend the previous work by studying additional Brazilian admixed individuals and examining DNA sequencing data from the ch 8p23.1 candidate region. Thus, we inferred the local ancestry of 125 exomes from individuals born in five towns within the Southeast region of Brazil (São Paulo, Campinas, Barretos, and Ribeirão Preto located in the state of São Paulo and Belo Horizonte, the capital of the state of Minas Gerais), and compared to data from two public Brazilian reference genomic databases, BIPMed and ABraOM, and with information from the 1000 Genomes Project phase 3 and gnomAD databases. Our results revealed that ancestry is similar among individuals born in the five Brazilian towns assessed; however, an increased proportion of sub-Saharan African ancestry was observed in individuals from Belo Horizonte. In addition, individuals from the five towns considered, as well as those from the ABRAOM dataset, had the same overrepresentation of Native-American ancestry on the ch 8p23.1 locus that was previously reported for the BIPMed reference sample. Sequencing analysis of ch 8p23.1 revealed the presence of 442 non-synonymous variants, including frameshift, inframe deletion, start loss, stop gain, stop loss, and splicing site variants, which occurred in 24 genes. Among these genes, 13 were associated with obesity, type II diabetes, lipid levels, and waist circumference (PRAG1, MFHAS1, PPP1R3B, TNKS, MSRA, PRSS55, RP1L1, PINX1, MTMR9, FAM167A, BLK, GATA4, and CTSB). These results strengthen the hypothesis that a set of variants located on ch 8p23.1 that result from positive selection during early admixture events may influence obesity-related disease predisposition in admixed individuals of the Brazilian population. Furthermore, we present evidence that the exploration of local ancestry deviation in admixed individuals may provide information with the potential to be translated into health care improvement.

Genetic variability in COVID-19-related genes in the Brazilian population.

SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different host ACE2 and TMPRSS2 genetic backgrounds might contribute to differences in the rate of SARS-CoV-2 infection or COVID-19 severity. Recent studies have also shown that variants in 15 genes related to type I interferon immunity to influenza virus might predispose patients toward life-threatening COVID-19 pneumonia. Other genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, IL6, CTSL, ABO, and FURIN) and HLA alleles have also been implicated in the response to infection with SARS-CoV-2. Currently, Brazil has recorded the third-highest number of COVID-19 cases worldwide. We aimed to investigate the genetic variation present in COVID-19-related genes in the Brazilian population. We analyzed 27 candidate genes and HLA alleles in 954 admixed Brazilian exomes. We used the information available in two public databases (http://www.bipmed.org and http://abraom.ib.usp.br/) and additional exomes from individuals born in southeast Brazil, the region of the country with the highest number of COVID-19 patients. Variant allele frequencies were compared with the 1000 Genomes Project phase 3 (1KGP) and gnomAD databases. We detected 395 nonsynonymous variants; of these, 325 were also found in the 1KGP and/or gnomAD. Six of these variants were previously reported to influence the rate of infection or clinical prognosis of COVID-19. The remaining 70 variants were identified exclusively in the Brazilian sample, with a mean allele frequency of 0.0025. In silico analysis revealed that seven of these variants are predicted to affect protein function. Furthermore, we identified HLA alleles previously associated with the COVID-19 response at loci DQB1 and DRB1. Our results showed genetic variability common to other populations and rare and ultrarare variants exclusively found in the Brazilian population. These findings might lead to differences in the rate of infection or response to infection by SARS-CoV-2 and should be further investigated in patients with this disease.

Multi-omics analysis suggests enhanced epileptogenesis in the Cornu Ammonis 3 of the pilocarpine model of mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the occurrence of seizures, and histopathological abnormalities in the mesial temporal lobe structures, mainly hippocampal sclerosis (HS). We used a multi-omics approach to determine the profile of transcript and protein expression in the dorsal and ventral hippocampal dentate gyrus (DG) and Cornu Ammonis 3 (CA3) in an animal model of MTLE induced by pilocarpine. We performed label-free proteomics and RNAseq from laser-microdissected tissue isolated from pilocarpine-induced Wistar rats. We divided the DG and CA3 into dorsal and ventral areas and analyzed them separately. We performed a data integration analysis and evaluated enriched signaling pathways, as well as the integrated networks generated based on the gene ontology processes. Our results indicate differences in the transcriptomic and proteomic profiles among the DG and the CA3 subfields of the hippocampus. Moreover, our data suggest that epileptogenesis is enhanced in the CA3 region when compared to the DG, with most abnormalities in transcript and protein levels occurring in the CA3. Furthermore, our results show that the epileptogenesis in the pilocarpine model involves predominantly abnormal regulation of excitatory neuronal mechanisms mediated by N-methyl D-aspartate (NMDA) receptors, changes in the serotonin signaling, and neuronal activity controlled by calcium/calmodulin-dependent protein kinase (CaMK) regulation and leucine-rich repeat kinase 2 (LRRK2)/WNT signaling pathways.

Parents' Emotional and Social Experiences of Caring a Child with Cleft Lip and/or Palate

ABSTRACT Objective: To evaluate the emotional and social experiences of parents or caregivers of children with cleft lip and/or palate (CL/P) in a city in the Northeastern of Brazil. Material and Methods: A quantitative and cross-sectional study was conducted among parents or caregivers of children with CL/P by interviews based on a questionnaire. Interviews were conducted during the First Smile Project in Sobral, Ceará, Brazil. All participants (n=41) agreed to participate in the interview and signed an informed consent. The data was analyzed in SPSS software version 22.0. Results: The majority of participants were female (87.2%), with a mean age of 37 years, with a low level of education and low family income. The great majority (90.2%) of the parents were not prenatally diagnosed to have CL/P babies. Of those interviewed, 56.1% mentioned that the first diagnosis of cleft lip and palate was not presented by the professionals in a clarifying way to the family. Fear (36.6%) and sadness (19.5%) were the main feelings experienced when the child was diagnosed with fissure. Feeding (48.8%) was pointed out as the main concern in caring for a child with CL/P. Conclusion: The parents and caregivers interviewed faced important emotional and social problems that must be addressed by the professional team that assists the child with CL/P.