Effects of dexamethasone on the Li-pilocarpine model of epilepsy : protection against hippocampal inflammation and astrogliosis

Background: Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy. Methods: Initially, hippocampal slices were obtained from sham rats and rats subjected to the Li-pilocarpine model of epilepsy, at 1, 14, and 56 days after status epilepticus (SE), which correspond to the acute, silent, and chronic phases. Dexamethasone was added to the incubation medium to evaluate the secretion of S100B, an astrocyte-derived protein widely used as a marker of brain injury. In the second set of experiments, we evaluated the in vivo effect of dexamethasone, administrated at 2 days after SE, on hippocampal inflammatory (COX-1/2, PGE2, and cytokines) and astroglial parameters: GFAP, S100B, glutamine synthetase (GS) and water (AQP-4), and K+ (Kir 4.1) channels. Results: Basal S100B secretion and S100B secretion in high-K+ medium did not differ at 1, 14, and 56 days for the hippocampal slices from epileptic rats, in contrast to sham animal slices, where high-K+ medium decreased S100B secretion. Dexamethasone addition to the incubation medium per se induced a decrease in S100B secretion in sham and epileptic rats (1 and 56 days after SE induction). Following in vivo dexamethasone administration, inflammatory improvements were observed, astrogliosis was prevented (based on GFAP and S100B content), and astroglial dysfunction was partially abrogated (based on Kir 4.1 protein and GSH content). The GS decrease was not prevented by dexamethasone, and AQP-4 was not altered in this epileptic model. Conclusions: Changes in astroglial parameters emphasize the importance of these cells for understanding alterations and mechanisms of epileptic disorders in this model. In vivo dexamethasone administration prevented most of the parameters analyzed, reinforcing the importance of anti-inflammatory steroid therapy in the Li-pilocarpine model and possibly in other epileptic conditions in which neuroinflammation is present

Controle de qualidade e otimização de TCFC em um Acelerador Linear

A necessidade de tratamentos radioterápicos mais precisos abriu espaço para que novas ferramentas fossem utilizadas. A Tomografia Computadorizada de Feixe Cônico (TCFC) inova com boa resolução de baixo contraste. Com regulação de operação e controle de qualidade ainda não estabelecida no país, este trabalho busca criar um protocolo de garantia de qualidade e avaliar seus modos de exame para possível primoramento. Imagens foram adquiridas utilizando uma TC convencional Siemens Somaton, um LINAC Varian TrueBeam e uma variedade de fantomas para o controle de qualidade de imagem: Catphan e Rando (The Phantom Laboratory, Salem, NY, EUA) e Electron Density (CIRS). As medições de dose transmitida foram realizadas com fantomas CTDI (cabeça e pelve) e um fantoma PMMA projetado pelo hospital, combinados com câmaras de ionizção abertas. O protocolo de controle de qualidade deve ser acessível e reprodutível. Além disso, o trabalho confirmou a possibilidade de substituir o fantoma CTDI pelo de PMMA e que a diminuição do produto corrente-tempo atual em 270 mAs no modo de pelve pode reduzir o CTDIw em 3,6 mGy (aproximadamente 7,0%)

The Piwil1 N domain is required for germ cell survival in Atlantic salmon

Genetic introgression of farmed salmon into wild populations can damage the genetic integrity of wild stocks and is therefore considered as an environmental threat. One possible solution is to induce sterility in farmed salmon. We have searched for proteins potentially essential for germline survival in Atlantic salmon. One of these is the argonaute protein Piwil1, known to be required for germ cell survival. To examine Piwil1 function in salmon, we induced indels in the N domain by CRISPR-Cas9. The encoded domain is present in all vertebrate Piwi proteins and has been linked to Tdrd1 protein interaction and PAZ lobe structure. The F0 founder generation of piwil1 crispant males and females displayed a mosaic pattern of piwil1 mutations, exhibiting highly mutated alleles (53%–97%) in their fin gDNA samples. In general, piwil1 crispants carried germ cells, went through puberty and became fertile, although a transient and partial germ cell loss and delays during the spermatogenic process were observed in many male crispants, suggesting that Piwil1 functions during salmon spermatogenesis. By crossing highly mutated F0 founders, we produced F1 fish with a mixture of: loss-of-function alleles (−); functional in frame mutated alleles (+) and wt alleles (+). In F1, all piwil1−/− fish lacked germ cells, while piwil1+/+ siblings showed normal ovaries and testes. Yet, most juvenile F1 piwil1+/−males and females displayed an intermediate phenotype with a higher somatic/germ cell ratio without an increase in germ cell apoptosis, suggestive of a gene dose effect on the number of germ cells and/or insufficient replacement of lost germ cells in heterozygous fish. Interestingly, the two longest in-frame indels in the N domain also ensured germ cell loss. Hence, the loss of 4–6 aa in this region Phe130-Ser136 may result in crucial changes of the protein structure, potentially affecting piRNA binding of the PAZ lobe, and/or affecting the binding of Piwil1 interacting proteins such as Tdrd protein, with critical consequences for the survival of primordial germ cells. In conclusion, we show that loss of piwil1 leads to loss of germ cells in salmon and that part of the N domain of Piwil1 is crucial for its function.publishedVersio

Modulation of neuropeptide Y levels is impaired in crack withdrawal patients

Introduction: The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has a key role in drug addiction susceptibility. In addition to the well-known relationship between cortisol and the HPA axis, other molecules are involved with stress response and could modify the HPA activation, such as the neuropeptide Y (NPY), which has anxiolytic proprieties. There are few studies evaluating the effect of NPY levels on addiction, especially in crack cocaine dependence. Objective: To evaluate NPY in crack users during early withdrawal to determine its relationship with drug use and cortisol levels. Methods: We analyzed 25 male inpatient crack users. Serum NPY levels were measured at admission and discharge (mean of 24 days). Morning salivary cortisol was measured at admission. Results: Serum NPY levels at admission and discharge were very similar. Lower NPY levels at discharge were associated with higher lifetime crack use. Also, a negative correlation was found between morning cortisol and delta NPY (NPY discharge – NPY admission). Conclusion: These preliminary findings indicate that crack use influences the modulation of NPY levels and modifies stress response. The NPY pathway may play an important role in the pathophysiology of crack addiction, and the anxiolytic effect of NPY may be impaired in crack users. Future studies should consider NPY as a measurable indicator of the biological state in addiction

From extreme weather events to ‘cascading vulnerabilities’ : participatory flood research methodologies in Brazil during COVID-19

Extreme weather events are entangled with each other and with other extreme events, such as the COVID-19 pandemic, anti-racist protests, drought, a housing crisis, strikes, or climate emergencies, as well as with more general inadequacies due to national, economic, and political upheavals and accreted vulnerabilities from long-term policies or inactions. Effects of extreme weather events are intensified by ongoing social injustices like poverty and structural racism, a housing deficit, and the consequent informal and unplanned occupation of hazardous areas, such as riverbanks, and areas of previous social-environmental disasters. In the context of Brazil, the ongoing deforestation in the Amazon (agribusiness, mining and illegal wood) provoking droughts and energy shortages in the region creates further vulnerabilities that are felt globally. In this paper, our primary contribution to these inter-connected scenarios is to describe methodological interventions that were made in response to COVID-19, and to show how those changes provided new insights into vulnerability processes of both subjects and researchers. During a larger project (Waterproofing Data), focused on the case study research areas of São Paulo and Acre (Brazil) wherein our wider team conducted flood-risk community research, we were forced to rethink our approach. We moved away from the singularity of the flood event and its impacts toward acknowledging the cascading conditions of social vulnerability (caused by weather, health, social and political conditions). In this paper, we directly address the ‘cascade of vulnerabilities’ that the flood-prone communities already encounter when researchers seek to engage with them. We open new avenues to reconsider citizenship, space, and innovation in terms of the key challenges that our methods encountered when conducting participatory flood research methodologies, particularly during the first phase of the COVID-19 pandemic from March 2020 to November 2021. Through flood research in Brazil, we articulate methodological contributions from the arts, humanities, and social sciences for more realistic, just, and caring research practices within and about weather in the context of ‘slow violence’ [Nixon, R (2013). Slow Violence and the Environmentalism of the Poor. Cambridge, MA: Harvard UP]

Inflammatory cytokines and alcohol use disorder : systematic review and meta-analysis

Objective: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC). Methods: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis. Results: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-a, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-g and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines. Conclusion: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking

The play behavior and its implications for child development according to Evolutionary Psychology

A brincadeira é uma atividade presente na vida de crianças em diversas culturas, possuindo papel importante no desenvolvimento das mesmas. Apesar disso, tal importância nem sempre é reconhecida pelos adultos, os quais priorizam na educação das crianças aspectos cognitivos formais e apresentam uma dificuldade em visualizar a relação existente entre brincadeira e desenvolvimento. A psicologia evolucionista tem voltado seu olhar para o brincar por este caracterizar-se como adaptado e adaptativo da espécie, contendo aspectos filogenéticos e ontogenéticos. Tal abordagem busca estudar as possíveis relações entre cultura e filogênese no desenvolvimento deste comportamento. Dessa forma o objetivo deste trabalho foi apresentar o brincar a partir do referencial teórico da psicologia evolucionista, bem como seu conceito e suas características. Além disso, são apresentadas as relações entre o brincar, os tipos de brincadeira e as diferenças de gênero. A brinquedoteca é apresentada como um possível espaço no qual esse comportamento pode ser estimulado e valorizado.The play behavior is an activity that is present in children's life in many cultures, having an important role in child development. However, such importance sometimes is not recognized by adults, who prioritize in children education formal cognitive aspects, and have difficulties in visualizing the relation between play and development. Evolutionary Psychology views play as a behavior that has evolutionary and ontogenetic aspects. Such approach intends to study the possible relations between culture and evolution in the development of this behavior. The objective of this paper is to present the play behavior based on the theoretical framework of Evolutionary Psychology, as well as its concept and characteristics. Moreover, the relations between playing, types of play and gender differences are discussed. The toy library is presented as a possible space in which this behavior can be stimulated and valued