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Mucormycosis is a severe fungal infection that demands immediate and decisive intervention upon suspicion. The causative agents of mucormycosis exhibit inherent resistance to echinocandins and voriconazole, and their in vitro susceptibility to terbinafine is highly variable and species-specific. Considering these factors and the limitations of currently available antifungal therapies, the identification of novel antifungals with potent activity against mucormycosis is of paramount importance. This study aims to identify compounds from the MMV Pathogen Box® presenting antifungal activity against selected mucormycosis agents and to evaluate their potential synergistic effects when combined with antifungal drugs. A screening of the Pathogen Box® compounds was conducted, isolated or in combination with sub-inhibitory concentrations of amphotericin B, isavuconazole or posaconazole, against a Rhizopus oryzae strain. Hits from the screenings were further evaluated against eight Mucoralean strains for minimal inhibitory and fungicidal concentration determinations and to confirm synergistic interactions using the checkerboard method. Ultrastructural studies were performed using scanning electron microscopy. MMV675968 exhibited fungicidal activity against a R. oryzae strain. All but one Rhizopus spp. strains presented MIC ≤ 1 µg/mL, with a geometric mean of 0.78 µg/mL observed across all isolates for this compound, which did not change significantly the cellular structure of this fungus. The combination screening with antifungal drugs revealed six additional compounds potentially active against the R. oryzae strain, two of them demonstrated proven synergism through the checkerboard assay. This first study with the MMV Pathogen Box® and Zigomycetes highlights promising new treatment options for mucormycosis in the future.
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Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.
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We evaluated neurologic complications following noncongenital Zika virus infection in 11 children who presented with central nervous system signs. Zika virus RNA was detected by real-time reverse transcription-polymerase chain reaction in cerebrospinal fluid. Approximately one-quarter of patients required antiepileptic medication in follow-up, and 2 children progressed to learning difficulties or developmental delay.
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Deficiências do Desenvolvimento/virologia , Deficiências da Aprendizagem/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/complicações , Anticonvulsivantes/uso terapêutico , Brasil , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Eletroencefalografia , Feminino , Hospitalização , Humanos , Lactente , Deficiências da Aprendizagem/diagnóstico , Masculino , Doenças do Sistema Nervoso/diagnóstico , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/psicologiaRESUMO
Background: The non-clinical presentation of obsessive-compulsive symptoms (OCS) in women may impact not only their daily lives and well-being but also increase the risk for emotional and behavioral problems in their children. This study aims to investigate the OCS dimension distribution in a large sample of mothers from a cohort of school age children and the association between these OCS dimensions with their own psychopathology, and with the presence of OCS and other psychopathology in their children. Method: Our final sample consisted of 2,511 mother-children dyads recruited from the elementary schools of two large cities. Throughout multiple regression analysis, we examined the correlations between demographic and clinical variables of mothers assessed by the Mini International Psychiatric Interview (MINI) and the Dimensional Yale-Brown Obsessive-Compulsive Scale-Short Version (DY-BOCS-SV) with children's psychopathology status reported by the Child Behavior Checklist (CBCL). Results: The overall prevalence of mothers who reported experiencing at least one OCS was 40% (N = 1,004). "Aggression/violence" was the most frequent symptom dimension (32.2%), followed by the "symmetry/ordering" (16.4%) and the "sexual/religious" dimensions (13.8%). There was a significant correlation between the presence of OCS and maternal psychopathology in general (p < 0.001, r = 0.397). Not only the presence but also the severity of the mother's OCS were strongly correlated to the total (p < 0.001), internalizing (p < 0.001), externalizing (p < 0.001), and OCS subscale scores (p < 0.001) on the CBCL. Conclusion: OCS dimensions are highly prevalent in women. Presence and severity of maternal OCS are related to children's psychopathology and behavioral problems.
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Background: Thalamic volume measures have been linked to obsessive-compulsive disorder (OCD) in children and adolescents. However, it is unclear if alterations in thalamic volumes occur before or after symptom onset and if there is a relation to the presence of sub-clinical obsessive-compulsive symptoms (OCS). Here, we explore the relationship between OCS and the rate of thalamic volume change in a cohort of children and youth at high risk to develop a mental disorder. A secondary aim was to determine if there is a relationship between OCS and the individual's OCD polygenic risk score (OCD-PRS) and between the rate of thalamic volume change and the OCD-PRS. Methods: The sample included 378 children enrolled in the longitudinal Brazilian High-Risk Cohort for Mental Conditions. Participants were assessed for OCS and the symmetrized percent change (SPC) of thalamic volume across two time-points separated by 3 years, along with the OCD-PRS. Zero-altered negative binomial models were used to analyze the relationship between OCS and thalamic SPC. Multiple linear regressions were used to examine the relationship between thalamic SPC and OCD-PRS. Results: A significant relationship between OCS and the right thalamus SPC (p = 0.042) was found. There was no significant relationship between changes in thalamic volume SPC and OCD-PRS. Conclusions: The findings suggest that changes in the right thalamic volume over the course of 3 years in children may be associated to OCS. Future studies are needed to confirm these results and further characterize the specific nature of OCS symptoms associated with thalamic volumes.
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BACKGROUND: Viruses are a common cause of central nervous system (CNS) infections. However, studies of CNS viral pathogens in pediatric patients are poorly explored because viral infections are often erroneously diagnosed as bacterial infections. METHODS: 299 CNS samples were collected from pediatric patients aged from one month to 14 years old. A total of 140 viral meningitis cases that met the inclusion criteria were included in this study. In 38 of the 140 cerebral spinal fluid (CSF) samples (27.1%), conventional and real-time PCR were used to identify viruses commonly associated with CNS infections. RESULTS: Among them, 23 patients (16.5%) tested positive for flaviviruses such as dengue, Zika, and yellow fever virus, eight patients (5.7%) were positive for enterovirus (ENTV), and six patients (4.3%) were positive for human herpesvirus 1/2. We also identified one case of dengue virus and ENTV co-infection. CONCLUSIONS: A correlation between clinical symptoms and laboratory findings for the viruses was identified. Our study also reinforces the importance of including viruses in the laboratory diagnosis of CNS infections especially flaviviruses, which assists public health authorities in implementing early interventions.
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Infecções do Sistema Nervoso Central , Viroses do Sistema Nervoso Central , Enterovirus , Meningite Viral , Viroses , Infecção por Zika virus , Zika virus , Adolescente , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/epidemiologia , Viroses do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Meningite Viral/diagnóstico , Meningite Viral/epidemiologia , Viroses/diagnóstico , Viroses/epidemiologiaRESUMO
Environmental factors are at least as important as genetic factors for the development of obsessive-compulsive symptoms (OCS), but the identification of such factors remain a research priority. Our study aimed to investigate the association between a broad scope of potential risk factors and OCS in a large community cohort of children and adolescents. We evaluated 1877 participants and their caregivers at baseline and after 3 years to assess various demographic, prenatal, perinatal, childhood adversity, and psychopathological factors. Mean age at baseline was 10.2 years (SD 1.9) and mean age at follow-up was 13.4 years (SD 1.9). Reports of OCS at baseline and follow-up were analyzed using latent variable models. At preliminary regression analysis, 15 parameters were significantly associated with higher OCS scores at follow-up. At subsequent regression analysis, we found that eight of these parameters remained significantly associated with higher follow-up OCS scores while being controlled by each other and by baseline OCS scores. The significant predictors of follow-up OCS were: lower socioeconomic status (p = 0.033); lower intelligence quotient (p = 0.013); lower age (p < 0.001); higher maternal stress level during pregnancy (p = 0.028); absence of breastfeeding (p = 0.017); parental baseline OCS (p = 0.038); youth baseline anxiety disorder (p = 0.023); and youth baseline OCS scores (p < 0.001). These findings may better inform clinicians and policymakers engaged in the mental health assessment and prevention in children and adolescents.
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Redes Comunitárias/normas , Transtorno Obsessivo-Compulsivo/psicologia , Psicopatologia/métodos , Criança , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Fatores de RiscoRESUMO
Introduction: Neural development is an enormously complex and dynamic process. From very early in brain development 'immune cells' play a key role in a number of processes including the formation and refinement of neural circuits, as well as sexual differentiation. There is a growing body of evidence that the immune system also plays an important role in the pathobiology of several neurodevelopmental and neuropsychiatric disorders. Objective: The goal of this article is to review the currently available data concerning the role of the 'immune system' in normal brain development, as well as its role in the pathobiology of neurodevelopmental and neuropsychiatric disorders. Methodology: We conducted a traditional literature search using PubMed and recent special issues of journals to locate relevant review articles. Results: The cellular and molecular processes that make up our 'immune system' are crucial to normal brain development and the formation and maintenance of neural circuits. It is also increasingly evident that the immune system and neuroinflammation play important roles in the pathobiology of at least a subset of individuals with Autism Spectrum Disorder (ASD), schizophrenia, obsessive-compulsive disorder, Tourette syndrome and mood disorders, such as depression, as well as autoimmune and neurodegenerative disorders. Emerging evidence also points to the importance of the 'gut-brain axis' and an individual's microbiome, which can impact an individual's somatic and mental well-being. Conclusions: There are multidirectional interconnections across multiple biological systems in our brains and bodies that are mediated in part by the immune system. At present, however, the 'promise' of this field remains greater than the 'deliverables'. Time will tell whether novel interventions will be developed that will make a positive difference in the care of our patients. It is also possible that valid biomarkers will emerge that will guide a more personalized approach to treatment.
Introdução: O desenvolvimento neural é um processo extremamente complexo e dinâmico. Tao pronto se inicia o desenvolvimento do cérebro, as "células imunológicas" desempenham um papel fundamental em vários processos, incluindo a formação e aperfeiçoamento de circuitos neurais, bem como a diferenciação sexual. Há um crescente corpo de evidências de que o sistema imunológico também desempenha um papel importante na fisiopatologia de diversos transtornos neurodesenvolvimentais e neuropsiquiátricos. Objetivo: O objetivo deste artigo é revisar os dados atualmente disponíveis sobre o papel do "sistema imunológico" em relação ao desenvolvimento normal do cérebro, bem como a fisiopatogenia dos transtornos de neurodesenvolvimento e neuropsiquiátricos. Metodologia: Foi realizada uma pesquisa bibliográfica tradicional para localizar artigos de revisão relevantes. Resultados: Os processos celulares e moleculares que compõem o nosso "sistema imunológico" são cruciais para o desenvolvimento normal do cérebro e a formação e manutenção de circuitos neurais. É cada vez mais evidente que o sistema imunológico e neuroinflamação desempenham papéis importantes na etiopatogenia de pelo menos um subconjunto de indivíduos com autismo, esquizofrenia, transtorno obsessivo-compulsivo, síndrome de Tourette, depressão e transtornos do humor, bem como distúrbios autoimunes e neurodegenerativos. Evidências emergentes também apontam para a importância do eixo intestino-cerebral e do microbioma de um indivíduo em relação à sua saúde e bem-estar somático e mental. Conclusões: Existem interconexões multidirecionais entre múltiplos sistemas biológicos em nossos cérebros e corpos que são mediados em parte pelo sistema imunológico. No momento, no entanto, a "promessa" desse campo continua sendo maior do que os "resultados finais". O tempo dirá se novas intervenções serão desenvolvidas que farão uma diferença positiva no cuidado de nossos pacientes. Também é possível que surjam biomarcadores válidos que orientarão uma abordagem mais personalizada ao tratamento.
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Transtorno Autístico , Neuroimunomodulação , Síndrome de Tourette , Microglia , Transtornos do Humor , Transtornos do Neurodesenvolvimento , Transtorno do Espectro Autista , Sistema Imunitário , Imunidade Materno-Adquirida , Transtorno Obsessivo-Compulsivo , Esquizofrenia , Estresse Psicológico , Citocinas , Depressão , Alergia e ImunologiaRESUMO
We report a 3-year-old child who was hospitalized because of severe manifestations of the central nervous system. The child died after 6 days of hospitalization. Analysis of postmortem cerebrospinal fluid showed the presence of yellow fever virus RNA. Nucleotide sequencing confirmed that the virus was wild-type yellow fever virus.
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RNA Viral/genética , Febre Amarela/líquido cefalorraquidiano , Febre Amarela/virologia , Vírus da Febre Amarela/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Autopsia , Biomarcadores , Brasil , Pré-Escolar , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Filogenia , Análise de Sequência de DNA , Avaliação de Sintomas , Tomografia Computadorizada por Raios X , Febre Amarela/diagnóstico , Febre Amarela/tratamento farmacológico , Vírus da Febre Amarela/classificação , Vírus da Febre Amarela/isolamento & purificaçãoRESUMO
PURPOSE: Areal bone mineral density (aBMD) by DXA is underestimated in those with smaller bones and overestimated in those with larger bones. Trabecular bone score (TBS) predicts fracture risk, and is not influenced by bone size. The aim of this study was to evaluate TBS and BMD in women with short stature. METHODS: We retrospectively analyzed DXA scans of all women aged 50-90 years with short stature (<144 cm) obtained in a single center, from 2006 to 2016. The comparison group comprised women >161 cm in height, matched for age and LS BMD, selected from the same database. RESULTS: The study population included 342 women. The two groups were similar in age, and aBMD at the LS and total hip. Femoral neck aBMD was lower in cases than in taller women. In contrast, TBS was higher in women with short stature than in their taller counterparts (1.347 ± 0.102 vs. 1.250 ± 0.110; p < 0.001). Bone mineral apparent density (BMAD) and the LS TBS-adjusted BMD T-score were also significantly higher in shorter than in taller women. From the entire cohort, 121 women (67 cases) were osteoporotic by aBMD determinations. Among these subjects, TBS was also greater in cases (1.303 ± 0.103) than in women with standard height (1.190 ± 0.099; p < 0.001). Despite being considered osteoporotic, 36% of short women, but none of the taller ones, had a normal TBS. CONCLUSIONS: TBS can be a useful adjunct to aBMD for assessing bone quality in short women, in whom aBMD measurement tends to read lower, and, thus could overestimate fracture risk.
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Estatura , Densidade Óssea/fisiologia , Osso Esponjoso/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Fraturas por Osteoporose/prevenção & controle , Ossos Pélvicos/diagnóstico por imagem , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de RiscoRESUMO
A 7-year-old boy that presented an encephalomyeloradiculitis and no classic symptoms of arboviruses. Zika virus (ZIKV) was confirmed by molecular analyses of cerebrospinal fluid and 1 year later by plaque reduction neutralization test. This case demonstrates that ZIKV can be associated with diffuse nervous system infection in children.
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Mielite/virologia , Radiculopatia/virologia , Infecção por Zika virus/complicações , Criança , Humanos , MasculinoRESUMO
BACKGROUND: Mental disorders are common health problems associated with serious impairment and economic impact. AIMS: To estimate the costs of clinical and subthreshold mental disorders in a sample of Brazilian children. METHOD: The High Risk Cohort Study is a community study conducted in two major Brazilian cities. Subjects were 6-14 years old children being registered at school. From an initial pool of 9937 children, two subgroups were further investigated using a random-selection (n = 958) and high-risk group selection procedure (n = 1554), resulting in a sample of 2512 subjects. Mental disorder assessment was made using the Development and Well-Being Assessment. Costs for each child were estimated from the following components: mental health and social services use, school problems and parental loss of productivity. RESULTS: Child subthreshold and clinical mental disorders showed lifetime mean total cost of $1750.9 and $3141.2, respectively. National lifetime cost estimate was $9.9 billion for subthreshold mental disorders and $11.6 billion for clinical mental disorders (values in US$ purchasing power parity). CONCLUSIONS: This study provides evidence that child mental disorders have a great economic impact on society. There is an urgent need to plan an effective system of care with cost-effective programs of treatment and prevention to reduce economic burden.
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Efeitos Psicossociais da Doença , Transtornos Mentais/economia , Adolescente , Brasil , Criança , Estudos de Coortes , Eficiência , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Serviços de Saúde Mental , Serviço SocialRESUMO
Importance: Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. Objective: To test the safety and study the outcome of DBS in patients with PWS. Design, Setting, and Participants: This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. Exposure: Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). Main Outcomes and Measures: Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. Results: Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. Conclusions and Relevance: Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.
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Estimulação Encefálica Profunda , Hipotálamo/cirurgia , Obesidade Mórbida/etiologia , Obesidade Mórbida/cirurgia , Síndrome de Prader-Willi/complicações , Adolescente , Adulto , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: The aims of this study were (1) to assess obsessive-compulsive symptoms (OCS) dimensionally in a school-aged community sample and to correlate them with clinical and demographical variables; (2) to determine a subgroup with significant OCS ("at-risk for OCD") using the Child Behavior Checklist (CBCL-OCS) and (3) to compare it with the rest of the sample; (4) To review the CBCL-OCS subscale properties as a screening tool for pediatric OCD. METHODS: Data from the Brazilian High Risk Cohort were analyzed. The presence and severity of OCS were assessed through the CBCL-OCS subscale. DSM-IV psychiatric diagnoses were obtained by the Developmental and Well-Being Assessment. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire, the Youth Strengths Inventory, and the CBCL internalizing and externalizing behavior subscales. RESULTS: A total of 2512 (mean age: 8.86 ± 1.84 years; 55.0% male) children were included. Moderate correlations were found between OCS severity and functional impairment (r = 0.36, p < 0.001). Children with higher levels of OCS had higher rates of psychiatric comorbidity and behavioral problems (p < 0.001). A score of 5 or higher in the CBCL-OCS scale determined an "at-risk for OCD" subgroup, comprising 9.7% of the sample (n = 244), with behavioral patterns and psychiatric comorbidities (e.g., tics [odds ratios, OR = 6.41, p < 0.001]), anxiety disorders grouped [OR = 3.68, p < 0.001] and depressive disorders [OR = 3.0, p < 0.001] very similar to those described in OCD. Sensitivity, specificity, positive predictive value, and negative predictive value of the CBCL-OCS for OCD diagnosis were, respectively, 48%, 91.5%; 15.1%, and 98.2%. CONCLUSIONS: The dimensional approach suggests that the presence of OCS in children is associated with higher rates of comorbidity, behavioral problems, and impairment. The "at-risk for OCD" group defined by the CBCL revealed a group of patients phenotypically similar to full blown OCD.
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Lista de Checagem/estatística & dados numéricos , Transtornos do Comportamento Infantil/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Comportamento Problema/psicologia , Transtornos de Ansiedade/diagnóstico , Brasil , Criança , Transtornos do Comportamento Infantil/epidemiologia , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricosRESUMO
To determine the causes of viral meningitis, we analyzed 22 cerebrospinal fluid samples collected during the 2014-2015 dengue epidemics in Brazil. We identified 3 serotypes of dengue virus (DENV-1, -2, and -3), as well as co-infection with 2 or 3 serotypes. We also detected the Asian II genotype of DENV-2.
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Vírus da Dengue/classificação , Dengue/epidemiologia , Meningite Viral/epidemiologia , Filogenia , Brasil/epidemiologia , Criança , Pré-Escolar , Coinfecção , Dengue/líquido cefalorraquidiano , Dengue/diagnóstico , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Feminino , Genótipo , Humanos , Lactente , Masculino , Meningite Viral/líquido cefalorraquidiano , Meningite Viral/diagnóstico , Meningite Viral/virologia , RNA Viral/genética , SorogrupoRESUMO
Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS) has been investigated as a neurosurgical modality to treat various neuropsychiatric disorders. In this article we review the rationale for selecting different brain targets, surgical results and future perspectives for the use of DBS in medically refractory obesity.
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Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two "in silico" protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.