The Domestication of Machismo in Brazil: Motivations, Reflexivity, and Consonance of Religious Male Gender Roles.

The relationship between culture and the individual is a central focus of social scientific research. This paper examines motivations that mediate between shared culture norms and individual actions. Inspired by the works of Leon Festinger and Melford Spiro, we posit that social network conformation (the perceived adherence of one's social network with norms) and internalization of cultural norms (incorporation of cultural models with the self-schema) will differentially shape behavior (cultural consonance) depending on the domain and individual characteristics. For the domain of gender roles among Brazilian men, religious affiliation results in different configurations of the individual and culture. Our findings suggest that, due to changing and competing cultural models, religious men are compelled to reflexively "think" about what masculinity means to them, rather than subconsciously conform to social (hegemonic) expectations. This study demonstrates the importance of considering the impetus of culturally informed behaviors and, in doing so, provides a methodological means for measuring and interpreting such motivations, an important factor in the relationship between culture and the individual.

Co-expression of PADI isoforms during progenitor differentiation enables functional diversity.

Protein isoforms, generated through alternative splicing or promoter usage, contribute to tissue function. Here, we characterize the expression of predicted Padi3α and Padi3ß isoforms in hair follicles and describe expression of Padi2ß, a hitherto unknown PADI2 isoform, in the oligodendrocyte lineage. Padi2ß transcription is initiated from a downstream intronic promoter, generating an N-terminally truncated, unstable, PADI2ß. By contrast to the established role of the canonical PADI2 (PADI2α) (Falcao et al. 2019 Cell Rep. 27, 1090-1102.e10. (doi:10.1016/j.celrep.2019.03.108)), PADI2ß inhibits oligodendrocyte differentiation, suggesting that PADI2 isoforms exert opposing effects on oligodendrocyte lineage progression. We localize Padi3α and Padi3ß to developing hair follicles and find that both transcripts are expressed at low levels in progenitor cells, only to increase in expression concomitant with differentiation. When expressed in vitro, PADI3α and PADI3ß are enriched in the cytoplasm and precipitate together. Whereas PADI3ß protein stability is low and PADI3ß fails to induce protein citrullination, we find that the enzymatic activity and protein stability of PADI3α is reduced in the presence of PADI3ß. We propose that PADI3ß modulates PADI3α activity by direct binding and heterodimer formation. Here, we establish expression and function of Padi2 and Padi3 isoforms, expanding on the mechanisms in place to regulate citrullination in complex tissues. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.

Distance from a cultural model of substance use risk, internalization, and self-stigma in urban Brazil.

Introduction: A cognitive theory of culture as socially distributed cultural models has proven useful in research. Cultural models exist in two forms: the model shared by individuals in a social group, and individual versions of that model modified by personal experience. In previous research we documented a shared cultural model of substance use risk among a general population sample in urban Brazil. Here we examine how this model is distributed among persons under treatment for substance use/misuse and the implications for perceived and self-stigma. Methods: A convenience sample of 133 persons under treatment rated the influence of risk factors for substance use/misuse. The configuration of those ratings and the cultural distance of persons under treatment from the general population model were calculated. Degree of stigma perceived in the wider society and degree of self-stigma were also assessed. Results: Persons under treatment aggregate risk factors to a greater extent than the general population. Using a cultural distance metric, the more distant persons under treatment are from the general population model, the lower their self-stigma regarding substance use. Discussion: Some individuals under treatment separate their understanding of substance use/misuse from shared perspectives in the wider society, which in turn reduces self-stigma. These findings add an additional perspective on the relationship of culture and the individual.

Gain-of-function STAT1 mutation and visceral leishmaniasis.

Gain-of-function mutations in the STAT1 gene have been initially associated with chronic mucocutaneous candidiasis. However, further research has shown that STAT1 GOF variants may increase susceptibility to infection by other intracellular pathogens. This report describes the first case of disseminated leishmaniasis associated with a STAT1 GOF mutation in a pediatric patient who did not have chronic mucocutaneous candidiasis. The patient was a four-year-old boy presenting with fever, severe asthenia, hepatosplenomegaly, pancytopenia, and liver failure. Bone marrow aspirate revealed hemophagocytosis and Leishmania parasites. Treatment consisted primarily of liposomal amphotericin B, as per the Hemophagocytic Lymphohistiocytosis 2004 protocol. After eight weeks of treatment, the patient did not improve and was submitted to diagnostic splenectomy. Activated macrophages and nodular spleen necrosis secondary to the visceral leishmaniasis were detected. Unfortunately, the patient died in the second week after splenectomy due to overwhelming systemic infection. DNA sequencing revealed a pathogenic (p. R274Q) GOF mutation in STAT1.

Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility.

Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG) and myelin by immune cells, which are thought to be the main drivers of MS susceptibility. We found that immune genes exhibit a primed chromatin state in single mouse and human OLG in a non-disease context, compatible with transitions to immune-competent states in MS. We identified BACH1 and STAT1 as transcription factors involved in immune gene regulation in oligodendrocyte precursor cells (OPCs). A subset of immune genes presents bivalency of H3K4me3/H3K27me3 in OPCs, with Polycomb inhibition leading to their increased activation upon interferon gamma (IFN-γ) treatment. Some MS susceptibility single-nucleotide polymorphisms (SNPs) overlap with these regulatory regions in mouse and human OLG. Treatment of mouse OPCs with IFN-γ leads to chromatin architecture remodeling at these loci and altered expression of interacting genes. Thus, the susceptibility for MS may involve OLG, which therefore constitutes novel targets for immunological-based therapies for MS.

Effects of Strength Training on Sleep Parameters of Adolescents: A Randomized Controlled Trial.

ABSTRACT: Santiago, LCS, Lyra, MJ, Germano-Soares, AH, Lins-Filho, OL, Queiroz, DR, Prazeres, TMP, Mello, MT, Pedrosa, RP, Falcão, APST, and Santos, MAM. Effects of strength training on sleep parameters of adolescents: a randomized controlled trial. J Strength Cond Res 36(5): 1222-1227, 2022-This study aimed to examine the effects of 12 weeks of strength training (ST) on sleep quality and daytime sleepiness in adolescents with sleep complaints. Thirty adolescents were randomly assigned to 2 groups: ST group (ST, n = 18) and control group (CG, n = 12). Anthropometric, body composition, one-repetition maximum test, and sleep parameters (Pittsburgh Sleep Quality Index [PSQI] and Epworth Sleepiness Scale [ESS]) were evaluated. Training consisted of 55 min·d-1 (3 times a week, for 12 weeks), 3 sets of 10-12 repetitions with a 1-minute rest interval between sets and exercises. Baseline and postintervention differences were analyzed using Generalized Estimating Equations and the effect size (ES) with Cohen's d coefficient. Significance was set at (p < 0.05). After 12 weeks of ST, a significant decrease in the PSQI score (7.3 ± 0.7 vs. 5.1 ± 0.6; ES = 4.10) was observed in the ST group, but not in the CG (6.3 ± 0.8 vs. 7.4 ± 0.7; ES = 1.53). A significant decrease in ESS score was found in the ST group (10.1 ± 0.7 vs. 8.2 ± 0.7; ES = 3.08), without differences in the CG (10.7 ± 0.8 vs. 11.0 ± 0.7; ES = 0.56). The ST group presented increased total sleep duration (h·min-1) (6.2 ± 0.2 vs. 6.9 ± 0.2; ES = 3.60), but not the CG (7.0 ± 0.2 vs. 6.8 ± 0.1; ES = 1.32). Individual analyses showed ≈67% of adolescents experienced a reduction in PSQI (8.3; confidence interval [CI] 95% 6.8-10.1) and ESS (8.3; CI 95% 6.7-9.9) scores after ST, whereas only ≈17% of control subjects presented reduced scores (PSQI [11.1; CI 95% 9.5-12.9] and ESS [11.0; CI 95% 9.4-12.6]). Strength training improved sleep quality and increased total sleep duration.

Gain-of-function STAT1 mutation and visceral leishmaniasis

ABSTRACT Gain-of-function mutations in the STAT1 gene have been initially associated with chronic mucocutaneous candidiasis. However, further research has shown that STAT1 GOF variants may increase susceptibility to infection by other intracellular pathogens. This report describes the first case of disseminated leishmaniasis associated with a STAT1 GOF mutation in a pediatric patient who did not have chronic mucocutaneous candidiasis. The patient was a four-year-old boy presenting with fever, severe asthenia, hepatosplenomegaly, pancytopenia, and liver failure. Bone marrow aspirate revealed hemophagocytosis and Leishmania parasites. Treatment consisted primarily of liposomal amphotericin B, as per the Hemophagocytic Lymphohistiocytosis 2004 protocol. After eight weeks of treatment, the patient did not improve and was submitted to diagnostic splenectomy. Activated macrophages and nodular spleen necrosis secondary to the visceral leishmaniasis were detected. Unfortunately, the patient died in the second week after splenectomy due to overwhelming systemic infection. DNA sequencing revealed a pathogenic (p. R274Q) GOF mutation in STAT1.

Variações linguísticas e seus efeitos na saúde:: reflexões para a clínica fonoaudiológica / Linguistic variations and their effects on health:: reflections for the speech therapy clinic / Variaciones lingüísticas y sus efectos sobre la salud:: reflexiones para la clínica de logopedia

Introdução: As variações linguísticas não correspondem a distúrbios de comunicação, entretanto a sua valoração, constitui fonte de preconceito linguístico e discriminação social, chegando a processos de "patologização". Falantes de variações linguísticas não prestigiadas, supondo algum distúrbio, procuraram o serviço de saúde com queixa de sofrer discriminação por preconceito linguístico. Experimentavam sensação de inferioridade, retraimento social, até rebaixamento da autoestima; levando a crises de ansiedade ou a episódios depressivos. Objetivo: Analisar as repercussões das variações linguísticas em um grupo de sujeitos, estabelecer indicações à reflexão sobre essa problemática no campo da saúde, especialmente no manejo dessas repercussões no âmbito da clínica fonoaudiológica. Método: Estudo de natureza descritiva, caracterizado, em seu desenho, como estudo de caso. Utilizou-se a metodologia do Grupo de Discussão, que consiste em favorecer e promover a construção de discurso grupal; sendo este o objeto da pesquisa. Resultados e Discussão: As variações linguísticas são constituídas em função de origem, extração sociocultural e condição socioeconômica e foram percebidas como variável significativa da discriminação e exclusão social. As categorias analíticas depreendidas do discurso grupal: preconceito e bullying; comunidade de fala e exclusão social; expectativas frente à norma prestigiada. O trabalho fonoaudiológico deverá: - reconhecer e valorizar o sofrimento das vítimas; - promover o trânsito pelas variações linguísticas, entender nuances fonético-fonológicas, sintáticas, semânticas e prosódicas, avaliando os usos e contextos sociais dos gêneros discursivos orais. Conclusão: Indicar à Fonoaudiologia para acolher e atender as vítimas de preconceito linguístico, no âmbito da ação clínica de prevenção de agravos e de promoção da saúde.

Introduction:  Linguistic variations do not correspond to communication disorders; however, their valuation constitutes a source of linguistic prejudice and social discrimination, reaching processes of "pathologization". Speakers of non-prestigious linguistic variations, assuming some speech disorder, sought the health service with a complaint of suffering discrimination due to linguistic prejudice. They experienced a sensation of inferiority, social withdrawal, even lowering of self-esteem; leading to bouts of anxiety or depressive episodes. Objective: To analyze the repercussions of linguistic variations in a group of people, establish indications for reflection on this problem in the field of health, especially in the management of these repercussions in the field of speech therapy. Methods: 'Descriptive Research' characterized, in it's design, as a case study. The 'Focus Group Discussion' methodology was used, which consists in favoring and promoting the construction of a group discourse; this being the object of the research. Results: The linguistic variations are constituted in function of origin, socio-cultural extraction and socioeconomic condition and were perceived as a significant variable of discrimination and social exclusion. The analytical categories inferred from the focus group: prejudice and bullying; the speech community and social exclusion; expectations in relation to the prestigious norm. The Speech therapy work should: - recognize and value the suffering of victims; - promote the transit through linguistic variations, understanding phonetic-phonological, syntactic, semantic and prosodic nuances, evaluating the uses and social contexts of oral discourse genders. Conclusion: To indicate the Speech therapy to welcome and assist the victims of linguistic prejudice, in the scope of the clinical action of prevention and health promotion.

Introduccion: Las variaciones lingüísticas no corresponden a los trastornos de la comunicación, sin embargo su valoración es fuente de prejuicios lingüísticos y de discriminación social, lo que conduce a procesos de "patologización". Los hablantes de variaciones lingüísticas no prestigiosas, asumiendo algún trastorno del habla, buscaron el servicio de salud quejándose de discriminación por prejuicios lingüísticos. Experimentaban una sensación de inferioridad, de retraimiento social, incluso de disminución de la autoestima; lo que provocaba crisis de ansiedad o episodios depresivos. Objetivo: Analizar las repercusiones de las variaciones lingüísticas en un grupo de sujetos, establecer indicaciones para la reflexión sobre este problema en el campo de la salud, especialmente en el manejo de estas repercusiones en el campo de la logopedia. Metodos:  Un 'Estudio Descriptivo', caracterizado en su diseño como un estudio de caso. Se utilizó la metodología del 'Grupo de Discusión', que consiste en favorecer y promover la construcción de un discurso grupal, siendo éste el objeto de la investigación. Resultados: Las variaciones lingüísticas se constituyen en función del origen, la extracción sociocultural y la condición socioeconómica y se perciben como una variable significativa de discriminación y exclusión social. Las categorías analíticas deducidas del discurso de grupo: prejuicios e intimidación; la comunidad de discurso y la exclusión social; expectativas en relación con la norma de prestigio. El trabajo logopedista debería: - reconocer y valorar el sufrimiento de las víctimas; - promover el tránsito por las variaciones lingüísticas, comprendiendo los matices fonético-fonológicos, sintácticos, semánticos y prosódicos, evaluando los usos y contextos sociales de los géneros del discurso oral. Conclusión: Indicar a Logopedia que acoja y asista a las víctimas de los prejuicios lingüísticos, en el ámbito de la acción clínica de prevención y promoción de la salud.

Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction.

Purpose: We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. Methods: We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing. Results: AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation. Conclusions: We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation.

Condição de saúde bucal de pacientes oncológicos / Oral health condition for oncological patients

Este estudo teve como objetivo avaliar a condição de saúde bucal de pacientes em terapia oncológica. Trata-se de um estudo observacional transversal realizado no Centro OncoHematologico de Pernambuco (CEONHPE), vinculado ao Hospital Universitário Oswaldo Cruz (HUOC), da Universidade de Pernambuco (UPE). Foram incluídos no estudo pacientes com idade entre 1 e 19 anos, de ambos os sexos, totalizando uma amostra de 177 pacientes, dentre os quais 25 realizaram o índice de placa, 111 submeteram-se ao índice de Dentes Cariados, Perdidos e Obturados (CPOD) e 129 ao índice de Dentes Decíduos Cariados, Com Extração Indicada e Obturados (ceo-d). Foi realizada coleta de dados secundários obtidos nas fichas clínicas dos pacientes que estiveram em atendimento no ano de 2018. Através da análise estatística descritiva foram consideradas as variáveis: condição de saúde bucal, idade, gênero, diagnóstico oncológico e fase atual do tratamento. Com relação às condições de saúde bucal foram avaliadas: condições de higiene oral (índice de placa de O´Leary); cárie (CPO-D e ceo-d). Verificou-se que houve predominância do índice CPO-D e ceo-d em zero e o índice de placa foi considerado insatisfatório na maioria dos pacientes. Portanto, apesar de baixo índice de cárie, foi constatado elevado índice de placa bacteriana...(AU)

This study aimed to assess the oral health condition of patients undergoing cancer therapy. This is a cross-sectional observational study carried out at the Centro OncoHematologico de Pernambuco (CEON-HPE), linked to the Hospital Universitário Oswaldo Cruz (HUOC), of the University of Pernambuco (UPE). The study included patients aged between 1 and 19 years old, of both sexes, totaling a sample of 177 patients, among whom 25 underwent the plaque index, 111 underwent the Decayed, Lost and Filled Teeth Index (CPOD) and 129 to the Decayed Deciduous Teeth Index, with Extraction Indicated and Filled (ceo-d). Secondary data were collected from the clinical records of patients who were in care in 2018. Through the descriptive statistical analysis, the variables were considered: oral health condition, age, gender, cancer diagnosis and current treatment stage. Regarding oral health conditions, the following were evaluated: oral hygiene conditions (O´Leary plaque index); caries (CPOD e ceo-d). It was found that there was a pre dominance of the CPOD index and ceo-d at zero and the plaque index was considered unsatisfactory in most patients. Therefore, despite a low rate of caries, a high rate of plaque was found... (AU)

Mapping heavy metal (Cu, Zn, and Pb) pollution and ecological risk assessment, in the surroundings of Gabes cement plant-Tunisia.

The pollution and contamination assessment of three heavy metals (Cu, Pb, and Zn) in the topsoil, and common plants (Olea europaea, Prunus persica vulgaris, Ficus carica, Medicago sativa, Zygophyllum album, and Helianthemum kahiricum) were carried out at different distances from a cement plant. This evaluation was based on four evaluation methods: Bioconcentration factor, Contamination factor, Geoaccumulation Index and Potential ecological risk factor. The chlorophylls a and b contents were also analyzed. The highest levels of Cu, Zn, and Pb in the topsoil were found close to the cement factory (cluster D), and the lowest values were observed in a distant oasis (cluster H). The lowest chlorophylls values were observed in perennial plants (O. europaea and F. carica) near the cement plant. Zygophyllum album and H. kahiricum showed capability to remove Cu an Zn in contaminated locations, depending on the soil type. The spatialization of the results was essential to the understanding of the potential contribution of different sources of Cu, Zn, and Pb in the topsoil and to distinguishing different behaviors of the same plant species. Concerning H. kahiricum, further research should be undertaken since it has a high livestock acceptability index and is used in traditional medicine. Novelty statement The impact of three heavy metals (Cu, Zn, and Pb) on the topsoil and six species of plants common in Tunisia (arid climate) will be assessed, and the potential contribution of different sources to the contamination. Few studies have addressed the impact of cement dust in the topsoil and common plant species in arid rangelands, and, as far as we know, none of them have considered the spatialization of the data and results, considering the prevailing wind, plant species location, soil type, and use. Moreover, the ability of steppic vegetation to remove these three heavy metals (phytoextraction) was evaluated using the bioconcentration factor (BCF), soil pollution indices, and ecological risk. Chlorophylls a and b contents were also evaluated to establish the effect of the cement plant on the health of plants located nearby.

Metotrexato em crianças e adolescentes com dermatite atópica: série de casos / Methotrexate in children and adolescents with atopic dermatitis: a case series

Introdução: A dermatite atópica é uma doença inflamatória crônica da pele que nas suas formas moderadas e graves afeta profundamente a qualidade de vida dos seus portadores e familiares. O metotrexato tem sido indicado off-label para casos graves e refratários em crianças e adolescentes, pois é uma opção terapêutica acessível e de baixo custo. Existe uma escassez de publicações envolvendo a medicação, sobretudo na faixa etária pediátrica. Objetivo e método: O presente estudo busca avaliar as características clínicas das crianças e adolescentes em uso atual ou prévio de metotrexato para tratamento de dermatite atópica moderada ou grave. Foram incluídos 10 pacientes, 60% do gênero masculino, mediana de idade no início do metotrexato de 14 anos (variando de 3 a 18 anos), e mediana do tempo de evolução da dermatite atópica de 14 anos (variando de 3 a 17 anos). Rinite alérgica e asma em 100% e 50% casos, respectivamente, e transtornos psíquicos em 60%. Resultados: Seis pacientes obtiveram melhora clínica com mediana de tempo de 9 meses (variando de 4 a 14 meses) e mediana do Scoring Atopic Dermatitis inicial de 50,5 (IIQ 13,8) e de 32,5 (IIQ 24,3) após 12 a 15 meses de tratamento. Efeitos adversos foram observados em 20% dos casos, e suspensão do metotrexato em apenas um paciente. Conclusão: Nesta série de casos com dez pacientes houve melhora clínica em seis, com poucos efeitos adversos, sendo uma alternativa terapêutica válida.

Introduction: Atopic dermatitis is a chronic inflammatory disease of the skin that in its moderate and severe forms profoundly affects the quality of life of patients and their families. Methotrexate has been used off-label for severe and refractory cases in children and adolescents, as it is an affordable and low-cost therapeutic option. There is a lack of publications addressing this medication, especially in the pediatric age group. Objective and method: The present study seeks to evaluate the clinical characteristics of children and adolescents in current or previous use of methotrexate for the treatment of moderate or severe atopic dermatitis. Ten patients were included, 60% were male, median age at the beginning of methotrexate use was 14 years (ranging from 3 to 18 years), and median time of course of atopic dermatitis was 14 years (ranging from 3 to 17 years). Allergic rhinitis and asthma were found in 100% and 50% of cases, respectively, and mental disorders in 60%. Results: Six patients achieved clinical improvement with a median time of 9 months (ranging from 4 to 14 months) and a median score in the initial Scoring Atopic Dermatitis of 50.5 (interquartile range, 13.8) and 32.5 (interquartile range, 24.3) after 12 to 15 months of treatment. Adverse effects were reported in 20% of cases, and methotrexate discontinuation in only one patient. Conclusion: In this case series of ten patients, methotrexate led to clinical improvement in six patients with few adverse effects, thus being a valid therapeutic alternative.

Microglia Susceptibility to Free Bilirubin Is Age-Dependent.

Increased concentrations of unconjugated bilirubin (UCB), namely its free fraction (Bf), in neonatal life may cause transient or definitive injury to neurons and glial cells. We demonstrated that UCB damages neurons and glial cells by compromising oligodendrocyte maturation and myelination, and by activating astrocytes and microglia. Immature neurons and astrocytes showed to be especially vulnerable. However, whether microglia susceptibility to UCB is also age-related was never investigated. We developed a microglia culture model in which cells at 2 days in vitro (2DIV) revealed to behave as the neonatal microglia (amoeboid/reactive cells), in contrast with those at 16DIV microglia that performed as aged cells (irresponsive/dormant cells). Here, we aimed to unveil whether UCB-induced toxicity diverged from the young to the long-cultured microglia. Cells were isolated from the cortical brain of 1- to 2-day-old CD1 mice and incubated for 24 h with 50/100 nM Bf levels, which were associated to moderate and severe neonatal hyperbilirubinemia, respectively. These concentrations of Bf induced early apoptosis and amoeboid shape in 2DIV microglia, while caused late apoptosis in 16DIV cells, without altering their morphology. CD11b staining increased in both, but more markedly in 2DIV cells. Likewise, the gene expression of HMGB1, a well-known alarmin, as well as HMGB1 and GLT-1-positive cells, were enhanced as compared to long-maturated microglia. The CX3CR1 reduction in 2DIV microglia was opposed to the 16DIV cells and suggests a preferential Bf-induced sickness response in younger cells. In conformity, increased mitochondrial mass and NO were enhanced in 2DIV cells, but unchanged or reduced, respectively, in the 16DIV microglia. However, 100 nM Bf caused iNOS gene overexpression in 2DIV and 16DIV cells. While only arginase 1/IL-1ß gene expression levels increased upon 50/100 nM Bf treatment in long-maturated microglia, MHCII/arginase 1/TNF-α/IL-1ß/IL-6 (>10-fold) were upregulated in the 2DIV microglia. Remarkably, enhanced inflammatory-associated microRNAs (miR-155/miR-125b/miR-21/miR-146a) and reduced anti-inflammatory miR-124 were found in young microglia by both Bf concentrations, while remained unchanged (miR/21/miR-125b) or decreased (miR-155/miR-146a/miR-124) in aged cells. Altogether, these findings support the neurodevelopmental susceptibilities to UCB-induced neurotoxicity, the most severe disabilities in premature babies, and the involvement of immune-inflammation neonatal microglia processes in poorer outcomes.

Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis.

Arrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in multiple sclerosis (MS) is associated with neurodegeneration and clinical worsening. We show that Glutathione S-transferase 4α (Gsta4) is highly expressed during adult OL differentiation and that Gsta4 loss impairs differentiation into myelinating OLs in vitro. In addition, we identify Gsta4 as a target of both dimethyl fumarate, an existing MS therapy, and clemastine fumarate, a candidate remyelinating agent in MS. Overexpression of Gsta4 reduces expression of Fas and activity of the mitochondria-associated Casp8-Bid-axis in adult oligodendrocyte precursor cells, leading to improved OL survival during differentiation. The Gsta4 effect on apoptosis during adult OL differentiation was corroborated in vivo in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis models, where Casp8 activity was reduced in Gsta4-overexpressing OLs. Our results identify Gsta4 as an intrinsic regulator of OL differentiation, survival and remyelination, as well as a potential target for future reparative MS therapies.

Exosome Circuitry During (De)(Re)Myelination of the Central Nervous System.

Reciprocal neuron-glia cell communication is fundamental for the proper function of the nervous system. Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that insulate and provide trophic support to neurons. This effective interaction is crucial not only for myelination but also for long-term axonal survival and neural connectivity. In recent years, exosomes have been portrayed as key players in intercellular interaction in the context of the healthy and diseased CNS. They act as communicating vehicles, true attachés operating between neurons and glial cells. Despite the complex exosome circuitry within the nervous system, experimental evidence supports the role of exosomes in modulating myelination. Oligodendrocytes secrete exosomes in response to neuronal signals in an electric activity-dependent manner. These released exosomes are then internalized by neurons, contributing to their integrity and activity. In turn, neurons secrete exosomes to control the communication between them and with myelinating cells in order to regulate synaptic function in neuronal development, myelin maintenance, and neuroregeneration. In this review, we provide a critical view of the current understanding on how exosomes, either from CNS-resident cells or from the periphery, contribute to the formation and maintenance of myelin and, additionally, on how the differential content of exosomes in normal and pathological conditions foresees the use of these nanovesicles as putative diagnostic and/or therapeutical agents in white matter degeneration-associated diseases.

Cadaveric ichthyofauna of the Madeira River in the Amazon basin: the myth of man-eating piranhas.

Drowned bodies rescued from the rivers of the Amazon basin exhibit several artefacts caused by the actions of the cadaveric ichthyofauna, namely, the "candiru". This study aims to review and discuss the fish species responsible for the largest number of attacks on bodies in the Madeira River (Porto Velho - Rondônia, Brazil), to describe the feeding strategies and types of lesions caused by each species, and to demystify the myth of the "man-eating piranhas". To the best of our knowledge, this study is the first that aims to provide a systematic analysis of cadaveric ichthyofauna and forensic findings in this region.