Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)

Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE/PRAAS carrying novel inherited proteasome missense and/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE/PRAAS associated genes, PSMB8 and PSMB10, whereas one patient showed additive loss-of-function mutations in PSMB8. Variants in two previously not associated proteasome genes, PSMA5 and PSMC5, were found in a patient who also carried the PSMB8 founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation

Transtorno bipolar em crianças: análise de relato de caso 2018-2023

O transtorno bipolar em crianças é uma realidade clínica que demanda atenção especializada. A compreensão dos sintomas, fatores de risco, prevalência e desafios diagnósticos é fundamental para proporcionar intervenções precoces e adequadas, visando melhorar a qualidade de vida desses jovens e reduzir o impacto a longo prazo dessa condição psiquiátrica. Trata-se de um estudo cujo objetivo foi objetivo revisar relatos de caso publicados entre 2018 e 2023 sobre transtorno bipolar em crianças, identificando o estado da arte desses estudos. Para isso, se realizou uma revisão sistemática de literatura utilizando as bases de dados Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientific Electronic Library Online (SCIELO). Com a análise e interpretação qualitativa dos resultados, a principal conclusão deste estudo é que o transtorno bipolar na infância é uma condição complexa, manifestando-se com comportamentos consistentes com o Transtorno de Conduta e sendo influenciado por fatores ambientais, familiares e genéticos. O tratamento eficaz requer uma abordagem multidisciplinar, integrando intervenções farmacológicas e não farmacológicas, personalizadas conforme as necessidades individuais. A supervisão familiar é crucial para a adesão ao tratamento, mas reconhece-se a necessidade contínua de pesquisa para aprimorar as estratégias terapêuticas diante da diversidade de casos

Cytokine profiling of samples positive for Chlamydia trachomatis and Human papillomavirus.

Persistent human papillomavirus (HPV) infection is closely associated with cervical carcinoma. Co-infection in the endocervical environment with other microorganisms, such as Chlamydia trachomatis, may increase the risk of HPV infection and neoplastic progression. While in some individuals, Chlamydia trachomatis infection is resolved with the activation of Th1/IFN-γ-mediated immune response, others develop a chronic infection marked by Th2-mediated immune response, resulting in intracellular persistence of the bacterium and increasing the risk of HPV infection. This work aimed to quantify cytokines of the Th1/Th2/Th17 profile in exfoliated cervix cells (ECC) and peripheral blood (PB) of patients positive for Chlamydia trachomatis DNA, patients positive for Papillomavirus DNA, and healthy patients. Cytokine levels were quantified by flow cytometry in ECC and PB samples from patients positive for C. trachomatis DNA (n = 18), patients positive for HPV DNA (n = 30), and healthy patients (n = 17) treated at the Hospital de Amor, Campo Grande-MS. After analysis, a higher concentration of IL-17, IL-6, and IL-4 (p <0.05) in ECC; INF-γ and IL-10 (p <0.05) in PB was found in samples from patients positive for C. trachomatis DNA compared to samples from healthy patients. When comparing samples from patients positive for HPV DNA, there was a higher concentration of cytokines IL-17, IL-10, IL-6, and IL-4 (p <0.05) in ECC and IL-4 and IL-2 (p <0.05) in PB of patients positive for C. trachomatis DNA. These results suggest that induction of Th2- and Th17 mediated immune response occurs in patients positive for C. trachomatis DNA, indicating chronic infection. Our results also demonstrate a high concentration of pro-inflammatory cytokines in ECC of patients positive for C. trachomatis DNA

A fetichização do livro didático no Brasil

Este artigo discutirá como as diversas polêmicas sobre a qualidade dos livros didáticos veiculadas pela imprensa nos últimos anos demonstram a supervalorização deste instrumento didático/pedagógico em nossa cultura escolar. Este status alcançado nas representações sociais pelos livros didáticos é resultado de uma complexa trajetória histórica, uma significativa relevância econômica, e de contornos ideológicos e políticos, sobretudo no período republicano brasileiro. Por fim, debaterá como a consagração deste material parece ofuscar outras discussões como as reais condições de trabalho, formação e aprendizado de professores e alunos brasileiros do ensino básico

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data