Search

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis—a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in FTL was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in HFE (c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both FTL and HFE genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.

Abstract Background Zika virus (ZIKV) infection gained public health concern after the 2015 outbreak in Brazil, when microcephaly rates increased in babies born from infected mothers. It was demonstrated that ZIKV causes a congenital Zika virus syndrome, including various alterations in the development of the central nervous system. Although the infection of cells from the nervous system has been well documented, less is known in respect of ZIKV ability to infect immune cells. Herein, we investigated if peripheral blood mononuclear cells (PBMCs), freshly-isolated from healthy donors, could be infected by ZIKV. Methods PBMCs from healthy donors were isolated and cultured in medium with ZIKV strain Rio-U1 (MOI = 0.1). Infection was analyzed by RT-qPCR and flow cytometry. Results We detected the ZIKV RNA in PBMCs from all donors by RT-qPCR analysis. The detection of viral antigens by flow cytometry revealed that PBMC from more than 50% the donors were infected by ZIKV, with CD3+CD4+ T cells, CD3−CD19+ B cells and CD3+CD8+ T cells being, respectively, the most frequently infected subpopulations, followed by CD14+ monocytes. Additionally, we observed high variability in PBMC infection rates among different donors, either by numbers or type infected cells. Conclusions These findings raise the hypothesis that PBMCs can act as a reservoir of the virus, which may facilitate viral dissemination to different organs, including immune-privileged sites.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) member of the Flaviviridae family, which has been associated with the development of the congenital Zika syndrome (CZS). RNA viruses, such as flaviviruses, have been reported to exert a profound impact on host microRNAs (miRNAs). Cellular miRNAs modulated by ZIKV may help identify cellular pathways of relevance to pathogenesis. Here, we screened 754 human cellular miRNAs modulated by ZIKV infection (Brazilian PE strain) in a neuroblastoma cell line. Seven miRNAs (miR-99a*, miR-126*, miR-190b, miR-361-3p, miR-522-3p, miR-299-5p, and miR-1267) were downregulated during ZIKV infection, while miR-145 was upregulated. Furthermore, 11 miRNAs were exclusively expressed in ZIKV-infected (miR-148a, miR-342-5p, miR-598, and miR-708-3p) or mock cells (miR-208, miR-329, miR-432-5p, miR-488, miR-518b, miR-520g, and miR-767-5p). Furthermore, in silico analysis indicated that some central nervous system, cellular migration, and adhesion function-related biological processes were overrepresented in the list of target genes of the miRNAs regulated in ZIKV-infected cells, especially for miR-145 and miR-148a. The induction of miR-145 and miR-148a was confirmed in postmortem brain samples from stillborn with severe CZS. Finally, we determined the expression regulation of microcephaly related genes through RNA interference pathway caused by ZIKV directly on neuron cells.

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

Introdução: No Brasil, estima-se a ocorrência de 704 mil casos novos de câncer para cada ano do triênio 2023-2025, sendo o câncer de cólon e reto (CCR) o tipo de neoplasia responsável pela terceira maior taxa de mortalidade para ambos os sexos. Objetivo: Analisar a tendência temporal de mortalidade prematura por CCR de 2006 a 2020, em ambos os sexos, no Brasil e em suas cinco Macrorregiões, e avaliar o alcance da meta proposta pelo Plano de Ações Estratégicas para o Enfrentamento das Doenças Crônicas não Transmissíveis no Brasil 2011-2022 do Ministério da Saúde (MS) em relação ao CCR. Método: Estudo de séries temporais das taxas de mortalidade prematura e padronizada de CCR (CID-10: C18-21) tendo como população de estudo a do Brasil, com dados obtidos a partir do Sistema de Informação sobre Mortalidade do DATASUS de 2006 a 2020. Resultados: As taxas de mortalidade prematura por CCR apresentaram aumento linear ao longo do período observado, porém com importantes diferenças regionais. Em relação ao CCR, a meta proposta pelo plano do MS não foi alcançada. Conclusão: Houve um aumento das taxas de mortalidade prematura por CCR no Brasil, tendência esperada em países em desenvolvimento. Por ser um câncer que envolve fatores de risco modificáveis, são importantes ações contínuas voltadas para o manejo desses fatores, tais como políticas nacionais de promoção de saúde. Além disso, são necessários estudos que subsidiem políticas preventivas de programas de rastreamento e diagnóstico precoce.

Objetivo: Descrever a experiência de um projeto de ação que consistiu em fomentar a reflexão e a aprendizagem sobre sexualidade saudável por meio da educação em saúde. Síntese dos dados: Trata-se de um relato de experiência de uma atividade de extensão universitária realizada em novembro de 2015, com envolvimento de graduandos e mestrandos, em uma unidade da Fundação Centro de Atendimento Socioeducativo do Adolescente – Fundação CASA, no município de São Paulo/SP, Brasil. Na experiência, houve participação de 75 adolescentes internos do sexo masculino. O projeto enfatizou o envolvimento dos adolescentes e gestores em etapas como: 1. Levantamento de questionamentos na temática; 2. Discussão e busca de fontes de pesquisa pelos mestrandos; 3. Elaboração, aplicação e avaliação do projeto de ação, em formato carrossel, alternando três grupos: anatomia e cuidados com o aparelho reprodutor masculino, doenças sexualmente transmissíveis (DSTs), e estilo de vida saudável e sexualidade. Conclusão: Por meio da ação educativa em saúde foi proposta a reflexão por um pensar a sexualidade, tanto na dimensão higiênica preventiva como na orientação a hábitos de vida promotores de saúde.

Enquadramento: A apreciação da qualidade de vida é basilar na compreensão do impacto causado pela hipertensão arterial. Objetivos: Caraterizar o perfil da população hipertensa da consulta externa de um hospital central, investigar a influência do estilo de vida na qualidade de vida relacionada com a saúde. Metodologia: Estudo quantitativo, descritivo, analítico, de corte transversal, com amostra de 105 utentes. Os instrumentos de colheita de dados incluem o Mini Questionário da Qualidade de Vida (MINICHAL) e Estilo de Vida Fantástico (EVF). Resultados: Verificámos que a perceção da qualidade de vida na vertente somática, é influenciada por estilos de vida nas dimensões família e amigos, nutrição, sono e stress, comportamentos de saúde e sexuais, bem como pelo consumo de tabaco. Relativamente à dimensão estado mental, verificámos fatores preditores nomeadamente, família e amigos, sono e stress, introspeção, comportamentos de saúde e sexuais e consumo de álcool. Conclusão: Considera-se que este estudo fornece informação útil para aumentar a efetividade dos programas de prevenção e controlo dos fatores de risco cardiovasculares.

OBJETIVO: Avaliar o efeito da corrente catódica de alta voltagem sobre a dor em um modelo experimental de ciatalgia. MÉTODOS: Foram utilizados 16 ratos Wistar, machos, submetidos a um modelo de ciatalgia experimental no membro pélvico direito. Os sujeitos foram divididos em grupo simulacro (GS) e grupo tratado com corrente catódica (GP-) por 20 min diários durante 10 dias. O modelo de compressão foi realizado com amarria por fio catgut 4.0 cromado, em quatro pontos ao longo do nervo isquiático. A avaliação da nocicepção foi realizada, de forma funcional, com o tempo de elevação da pata (TEP), e à pressão, pelo limiar de retirada, via analgesímetro eletrônico. Os dados foram coletados antes do modelo de ciatalgia (AV1), três dias depois da compressão (antes, AV2, e após o tratamento, AV3), após o quinto dia de tratamento (AV4) e em seguida ao décimo dia de tratamento (AV5). RESULTADOS: Pela avaliação funcional, em ambos os grupos houve aumento da nocicepção, sem redução da mesma em qualquer momento da avaliação. À pressão, no entanto, o GS mostrou redução do limiar de retirada em todos os momentos, enquanto o GP- apresentou redução do limiar apenas inicialmente - em AV5 o limiar foi restaurado. CONCLUSÃO: Não houve alteração na nocicepção pela avaliação funcional; porém, à pressão, o tratamento com corrente catódica mostrou efeito com a somatória de terapias.OBJECTIVE: To assess the effect of high-voltage cathodic current on pain from a sciatica experimental model. METHODS: A total of 16 male Wistar rats were submitted to the sciatica experimental model in the right hind paw. They were divided into sham group (GS) and group treated with cathodic current (GP-) for 20 min/daily, for 10 days). The model of sciatic compression was performed with a 4.0-chromic catgut thread tie in four points of the sciatic nerve. Assessment of nociception was performed by measuring the time during which the animal held its hind paw in a guarded position (THHP) and the pressure withdrawal threshold, by use of a digital electronic analgesymeter. Data collection was carried out before the sciatica experimental model (AS1), three days after compression (before, AS2, and after treatment, AS3), and five and 10 days after treatment (AS4 and AS5, respectively). RESULTS: According to the functional disability test, both groups showed an increase in nociception, with no reduction at any assessment time. Submitted to pressure, however, GS showed a reduction in the hind paw withdrawal threshold at all assessment times, while GP- showed a reduction in the hind paw withdrawal threshold only initially - at AS5, the threshold was restored. CONCLUSION: No change in nociception was observed on functional assessment; however, on pressure hind paw withdrawal assessment, the treatment with cathodic current showed to be effective with the summation of therapies.

Host factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. Here, we accessed samples from 153 pregnant women (77 without and 76 with CZS) and 143 newborns (77 without and 66 with CZS) exposed to ZIKV conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS outcome, and characterized placenta gene expression profile at term. Newborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.41; IC=1.35-8.60; Pcorrected=0.032). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. We found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. Despite of the low sample size se findings shed light on the host-pathogen interaction focusing on the genetically regulated type I/type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections.

Since the 2015 to 2016 outbreak in America, Zika virus (ZIKV) infected almost 900,000 patients. This international public health emergency was mainly associated with a significant increase in the number of newborns with congenital microcephaly and abnormal neurologic development, known as congenital Zika syndrome (CZS). Furthermore, Guillain–Barré syndrome (GBS), a neuroimmune disorder of adults, has also been associated with ZIKV infection. Currently, the number of ZIKV-infected patients has decreased, and most of the cases recently reported present as a mild and self-limiting febrile illness. However, based on its natural history of a typical example of reemerging pathogen and the lack of specific therapeutic options against ZIKV infection, new outbreaks can occur worldwide, demanding the attention of researchers and government authorities. Here, we discuss the clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. Several studies have confirmed the tropism of ZIKV for neural progenitor stem cells by demonstrating the presence of ZIKV in the central nervous system (CNS) during fetal development, eliciting a deleterious inflammatory response that compromises neurogenesis and brain formation. Of note, while the neuropathology of CZS can be due to a direct viral neuropathic effect, adults may develop neuroimmune manifestations such as GBS due to poorly understood mechanisms. Antiganglioside autoantibodies have been detected in multiple patients with ZIKV infection–associated GBS, suggesting a molecular mimicry. However, further additional immunopathological mechanisms remain to be uncovered, paving the way for new therapeutic strategies.

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn's genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10-5). The IL12RB2 gene (p-value: 2.18x10-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.

Gamma-aminobutyric acid (GABA) is used as a dietary supplement because of its health-promoting properties. However, concern over the use of synthetic products has increased the demand for foods that are naturally fortified with GABA. In addition, excess whey is a major concern for the dairy industry due to the high cost of treating it. Here, we report the use of a novel Enterococcus malodoratus strain isolated from cheese to produce sweet whey beverages naturally enriched with GABA. After the screening of cheese isolates, E. malodoratus strains were identified as high GABA producers. One beverage was prepared from pasteurized sweet whey enriched in glutamic acid and E. malodoratus SJC25. The fermented beverages were supplemented with a fruit preparation and subjected to chemical, microbiological and sensory analysis. The bacterial counts and GABA content were maintained until storage at 4 °C for 14 days. High conversion rates of glutamic acid to GABA (50–71%) were obtained in the beverages. The GABA content in whey-based beverages reached 250–300 mg/100 mL, which is equivalent to the content of commercially available GABA supplements. The beverages received a positive rating (4/5) by the taste panel. To our knowledge, this is the first report on E. malodoratus as a potential GABA producer.

Abstract: Sweet’s syndrome is a rare dermatosis with little-known pathogenesis, associated with some clinical conditions such as infections, autoimmune diseases, inflammatory bowel diseases, vaccination, medications and neoplasms. Hematologic malignancies are the diseases most related to paraneoplastic Sweet’s syndrome, but this clinical entity can also be found occasionally in some solid tumors, including genitourinary tract tumors. We report a rare case of paraneoplastic Sweet’s syndrome associated with the diagnosis of cervical cancer.

Synchronic melanomas are rare and poorly described in the literature. They are classified in this way when a second melanoma is observed on the first examination or up to three months after the first diagnosis. An unusual case and the dermoscopic examination of a patient with two primary synchronic melanomas is described. The dermatoscopy is a very useful tool in the early diagnosis of melanomas. Some dermatoscopy patterns suggestive of melanomas on the face are asymmetric pigmented anexiais openings, rhomboidal structures and blue-gray globules and dots. The dermatoscopy characteristic pattern of melanoma in the region of plant is the default in parallel ridges that has high sensitivity and specificity in detecting acrais melanomas.

Abstract: Clear cell acanthoma is an uncommon type of benign epithelial tumor. Typically, it is a solitary lesion found on the lower limbs. It presents as a nodule or small plaque with slow and well-defined growth. Diagnosis used to be clinical and histopathological, but the advent of dermoscopy has led to an increase in diagnostic accuracy. We describe a case in which dermoscopy proved highly useful for diagnosis of the lesion.

Objetivou-se verificar o efeito imediato da manipulação osteopática para anterioridade tibiotársica sobre o equilíbrio estático, em mulheres jovens. Metodologia: Vinte mulheres foram divididas igualmente em dois grupos: manipulação do tornozelo (GMT) e controle (GC). Analisou-se o deslocamento ântero-posterior (Y) e médio-lateral (X), de olhos abertos e fechados, em um Baropodômetro. Resultados: Na análise intergrupos, o GMT apresentou maior oscilação (eixos X e Y), em todos os momentos, comparado ao GC (p

INTRODUÇÃO: Existe certa controvérsia com relação ao efeito protetor do exercício em indivíduos com neuropatia periférica. OBJETIVO: Avaliar o treinamento físico, moderado e com intensidade progressiva, como fator infl uenciador da nocicepção em ratos submetidos a um modelo de ciatalgia. MATERIAIS E MÉTODOS: Foram utilizados 18 ratos, divididos em três grupos: Grupo-Controle (PL); Grupo Natação Baixa Intensidade (GNBI); Grupo Natação Tempo Progressivo (GNTP). Para a realização dos protocolos de treinamento, os animais foram colocados em tanque de água, durante 6 semanas, 3 dias da semana, sendo que para GNBI os animais realizavam 10 minutos de natação por dia, para GNTP os animais iniciaram com 10 minutos e tendo progressão de 10 minutos por semana. PL realizava menos de 1 minuto de natação, apenas para ambientalização. Após o treinamento foi realizado o modelo experimental de ciatalgia, com amarria por fio Catgut cromado. Para avaliação da nocicepção foi utilizado o Teste de Incapacidade Funcional, que mostra os valores de tempo de elevação da pata (TEP) em um minuto. As avaliações ocorreram antes da cirurgia, no 3º, 6º e 10º dias de pós-operatório (PO). RESULTADOS: Para todos os grupos, foi possível observar que houve aumento significativo dos valores no 3º, 6º e 10º dias de PO ao comparar com os valores do momento pré-cirurgia, mas, para o controle, não houve alteração significativa entre os momentos seguintes, fato que ocorreu para os grupos de natação. CONCLUSÃO: O exercício produziu maior hiperalgesia do que nos animais controle.INTRODUCTION: The protective effect of exercise on individuals with peripheral neuropathy is controversial. OBJECTIVE: To assess the influence of physical training of moderate and progressive intensity on nociception of rats in an experimental sciatica model. MATERIALS AND METHODS: The study assessed 18 rats divided into the following three groups: control group (CG); low-intensity swimming group (LISG); progressive-time swimming group (PTSG). To meet the physical training protocol, the animals were placed in a water tank for six weeks, three alternate days per week. In LISG group, the animals swam ten minutes per session, and, in PTSG group, the animals began swimming for ten minutes, and had a ten-minute increase per week. In CG group, the animals swam less than one minute per day, only to get used to the water environment. After finishing the swimming training, the experimental sciatica model protocol was started with constrictive ligature of the sciatic nerve with chromic catgut. Nociception was assessed using the functional disability test, which measures, in a one-minute interval, the time during which the animal holds its hind paw (THHP) in a guarded position. Assessments were performed preoperatively, and on the third, sixth, and tenth post-operative (PO) days. RESULTS: All groups showed a significant increase in THHP on third, sixth, and tenth PO days, as compared to preoperative values. In CG, no significant change was observed in PO assessments, unlike what happened in LISG and PTSG groups. CONCLUSION: Exercise produced greater hyperalgesia.

Este trabalho aborda a interpelação exercida pelo espaço urbano nos processos de subjetivação do homem contemporâneo, com especial atenção a situações relacionadas ao direito e ao uso do solo. É realizado um breve histórico do conceito de “uso social do solo” no país, de políticas públicas que vêm sendo implantadas com vistas à produção de habitação popular e à regularização fundiária de favelas e apresentadas impressões de moradores da favela da Rocinha, localizada na cidade do Rio de Janeiro, em face deste processo, ora em andamento em algumas de suas áreas. Os relatos dos moradores foram obtidos a partir dos trabalhos de campo realizados no âmbito da pesquisa “Espaço Urbano Contemporâneo e Subjetividade: um foco especial sobre as favelas do Rio de Janeiro”, sediada no Programa de Pós-Graduação em Psicologia Social, da UERJ, com apoio financeiro Prodoc/CAPES.

O artigo apresenta um estudo sobre o perfil do ensino de Contabilidade de Custos nos cursos de graduação em Administração do Estado de Santa Catarina. Trata-se de um estudo descritivo baseado em uma pesquisa documental, com abordagem qualitativa e quantitativa. Os dados foram coletados por meio de fontes primárias disponibilizadas nos planos de ensino das Instituições de Ensino Superior (IES) e a amostra examinada corresponde a 34,6% da população. O tópico mais citado nas ementas é terminologia de custos; as aulas expositivas ocupam o primeiro lugar do ranking de metodologias de ensino utilizadas; todas as IES que citam o sistema de avaliação no plano de ensino utilizam a prova como metodologia de verificação de aprendizagem; e o livro Contabilidade de Custos, de Eliseu Martins, é o mais citado nas bibliografias.