Microglia-dependent remodeling of neuronal circuits.

Microglia are tissue-resident macrophages responsible for the surveillance, neuronal support, and immune defense of the brain parenchyma. Recently, the role played by microglia in the formation and function of neuronal circuits has garnered substantial attention. During development, microglia have been shown to engulf neuronal precursors and participate in pruning mechanisms while, in the mature brain, they influence synaptic signaling, provide trophic support and shape synaptic plasticity. Recently, studies have unveiled different microglial characteristics associated with specific brain regions. This emerging view suggests that the maturation and function of distinct neuronal circuits may be potentially associated with the molecular identity microglia adopts across the brain. Here, we review and summarize the known role of these cells in the thalamus, hippocampus, cortex, and cerebellum. We focus on in vivo studies to highlight the characteristics of microglia that may be important in the remodeling of these neuronal circuits and in relation to neurodevelopmental and neuropsychiatric disorders.

Quantification and Improvement of the Dynamics of Human Serum Albumin and Glycated Human Serum Albumin with Astaxanthin/Astaxanthin-Metal Ion Complexes: Physico-Chemical and Computational Approaches.

Glycated human serum albumin (gHSA) undergoes conformational changes and unfolding events caused by free radicals. The glycation process results in a reduced ability of albumin to act as an endogenous scavenger and transporter protein in diabetes mellitus type 2 (T2DM) patients. Astaxanthin (ASX) in native form and complexed with metal ions (Cu2+ and Zn2+) has been shown to prevent gHSA from experiencing unfolding events. Furthermore, it improves protein stability of gHSA and human serum albumin (HSA) as it is shown through molecular dynamics studies. In this study, the ASX/ASX-metal ion complexes were reacted with both HSA/gHSA and analyzed with electronic paramagnetic resonance (EPR) spectroscopy, rheology and zeta sizer (particle size and zeta potential) analysis, circular dichroism (CD) spectroscopy and UV-Vis spectrophotometer measurements, as well as molecular electrostatic potential (MEP) and molecular docking calculations. The addition of metal ions to ASX improves its ability to act as an antioxidant and both ASX or ASX-metal ion complexes maintain HSA and gHSA stability while performing their functions.

Prevalence of Gastroesophageal Reflux Disease in Infants With Congenital Muscular Torticollis: A Prospective Cohort Study.

PURPOSE: Clinical experience suggests that gastroesophageal reflux disease (GERD) occurs commonly in infants with congenital muscular torticollis (CMT). However, this is an understudied topic and prospective studies are absent. We determine the prevalence of GERD in infants with CMT, comparing clinical characteristics between CMT infants with and without GERD, and identifying infants with potentially undiagnosed GERD. METHODS: A prospective cohort study of 155 infants with CMT younger than 12 months with and without GERD was evaluated by pediatric physical therapists. RESULTS: GERD prevalence was 30.3%, including 6 (3.9%) infants with undiagnosed GERD. Demographic and clinical characteristics were similar in CMT infants with and without GERD. CONCLUSIONS: This is the first prospective cohort study determining the prevalence of GERD in infants referred for evaluation of CMT. Further prospective studies are needed to determine whether early intervention and treatment of GERD improves outcomes in infants with CMT (see Supplemental Digital Content 1, available at: http://links.lww.com/PPT/A369).

Chemistry and anti-herpes simplex virus type 1 evaluation of 4-substituted-1H-1,2,3-triazole-nitroxyl-linked hybrids.

HSV disease is distributed worldwide. Anti-herpesvirus drugs are a problem in clinical settings, particularly in immunocompromised individuals undergoing herpes simplex virus type 1 infection. In this work, 4-substituted-1,2,3-1H-1,2,3-triazole linked nitroxyl radical derived from TEMPOL were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. The nitroxide derivatives were characterized by infrared spectroscopy and elemental analysis, and three of them had their crystal structures determined by single-crystal X-ray diffraction. Four hybrid molecules showed important anti-HSV-1 activity with IC50 values ranged from 0.80 to 1.32 µM. In particular, one of the nitroxide derivatives was more active than Acyclovir (IC50 = 0.99 µM). All compounds tested were more selective inhibitors than the reference antiviral drug. Among them, two compounds were 4.5 (IC50 0.80 µM; selectivity index CC50/IC50 3886) and 7.7 times (IC50 1.10 µM; selectivity index CC50/IC50 6698) more selective than acyclovir (IC50 0.99 µM; selectivity index CC50/IC50: 869). These nitroxide derivatives may be elected as leading compounds due to their antiherpetic activities and good selectivity.

Homogentisic Acid and Gentisic Acid Biosynthesized Pyomelanin Mimics: Structural Characterization and Antioxidant Activity.

Pyomelanin mimics from homogentisic acid (HGA) and gentisic acid (GA) were biosynthesized by the oxidative enzyme T. versicolor laccase at physiological pH to obtain water soluble melanins. The pigments show brown-black color, broad band visible light absorption, a persistent paramagnetism and high antioxidant activity. The EPR approach shows that at least two different radical species are present in both cases, contributing to the paramagnetism of the samples. This achievement can also shed light on the composition of the ochronotic pigment in the Alkaptonuria disease. On the other hand, these soluble pyomelanin mimics, sharing physico-chemical properties with eumelanin, can represent a suitable alternative to replace the insoluble melanin pigment in biotechnological applications.

Burning in southwestern Brazilian Amazonia, 2016-2019.

Fire is one of the most powerful modifiers of the Amazonian landscape and knowledge about its drivers is needed for planning control and suppression. A plethora of factors may play a role in the annual dynamics of fire frequency, spanning the biophysical, climatic, socioeconomic and institutional dimensions. To uncover the main forces currently at play, we investigated the area burned in both forested and deforested areas in the outstanding case of Brazil's state of Acre, in southwestern Amazonia. We mapped burn scars in already-deforested areas and intact forest based on satellite images from the Landsat series analyzed between 2016 and 2019. The mapped burnings in already-deforested areas totalled 550,251 ha. In addition, we mapped three forest fires totaling 34,084 ha. Fire and deforestation were highly correlated, and the latter occurred mainly in federal government lands, with protected areas showing unprecedented forest fire levels in 2019. These results indicate that Acre state is under increased fire risk even during average rainfall years. The record fires of 2019 may continue if Brazil's ongoing softening of environmental regulations and enforcement is maintained. Acre and other Amazonian states must act quickly to avoid an upsurge of social and economic losses in the coming years.

Influence of S. cerevisiae and P. kluyveri as starters on chocolate flavour.

BACKGROUND: Fermented cocoa beans (Theobroma cacao L.) are a pivotal raw material for chocolate production. A cocktail yeast applied in the cocoa fermentation process can promote the formation of pleasant metabolites. Saccharomyces, Pichia and Hanseniaspora have been widely used in fermentation to improve the final product organoleptic profile, highlighting that fermentation is a critical point for chocolate flavour precursor production. This study aims to evaluate the impact of Pichia kluyveri and Saccharomyces cerevisiae strains as starter cultures on the fermentation for two cocoa hybrids, FA13 and CEPEC2002. RESULTS: During fermentation processes, volatile organic compounds (VOCs) and protein profiles were assessed. Chocolates produced were also assessed regarding the presence of VOCs. Eighty VOCs were identified using gas chromatography coupled to mass spectrometry analysis. Mass spectrometry provided the protein profile evolution during fermentation and showed that the profiles changed with inoculation type (spontaneous versus inoculated fermentation). Chocolate obtained from FA13 inoculated with S. cerevisiae strain contained a greater amount of organics acids, being categorised as sourer than chocolate produced by spontaneous fermentation of FA13. CEPEC2002 inoculated with S. cerevisiae strain in co-culture with P. kluyveri strain generated less sour and sweeter chocolate than spontaneous fermentation only. CONCLUSIONS: Chocolates from inoculated assays with starter cultures were more accepted by evaluators, highlighting that P. kluyveri and S. cerevisiae influence the composition of VOCs. Besides, protein profiles also changed throughout fermentation. Further investigation should be conducted to clarify protein degradation dynamics during inoculated fermentations to define which of the microbial cultures positively affect the chocolate sensory characteristics. © 2021 Society of Chemical Industry.

Colostrum oropharyngeal immunotherapy for very low birth weight preterm infants: protocol of an intervention study.

BACKGROUND: The oropharyngeal colostrum administration protocol to treat premature newborns is a possible and plausible strategy in neonatal health services, since the immunoprotective components of colostrum can be absorbed by the lymphoid tissues of the oropharynx. In this context, this study aims to describe the implementation of oropharyngeal colostrum immunotherapy in very low birth weight preterm newborns in a neonatal unit, as well as to test an algorithm in a public hospital. METHODS: The protocol is applied in a non-randomized, superiority clinical trial with historical control. In the treatment group, 0.2 mL of raw colostrum is dripped into the right and left oropharyngeal mucosa, totaling 8 administrations every 24 h until the 7th complete day of life interruptedly. The control group consists of very low birth weight preterm newborns born in the same hospital in previous years (historical control). The clinical progression of 60 newborns until hospital discharge is recorded on standardized forms. A total of 350 participants are estimated to complete the survey in 4 years. The occurrence of continuous outcomes between the groups are compared through the paired t-test or Wilcoxon's two-sample test. The chi-square test or Fisher's exact test, and survival analysis are used for binary outcomes. The nutritional status is assessed through Intergrowth-21st growth curves for preterm newborns. DISCUSSION: The flows of the protocol's actions is sorted by an algorithm, compatible with the Brazilian reality of a public hospital. This measure facilitates and systematizes clinical care, organizes the team's work process, speeds up the intervention steps, standardizes decision-making and unifies the quality of care, besides showing the feasibility of oropharyngeal colostrum immunotherapy. TRIAL REGISTRATION: ReBEC, U1111-1222-0598 , Registered 09 October 2018, http://www.ensaiosclinicos.gov.br/rg/RBR-2cyp7c/ .

Spectroscopic Characterization of Natural Melanin from a Streptomyces cyaneofuscatus Strain and Comparison with Melanin Enzymatically Synthesized by Tyrosinase and Laccase.

An actinobacteria strain was isolated from Algerian Sahara soil and assigned to Streptomyces cyaneofuscatus Pridham et al. 1958 species. This strain was selected for its ability to produce melanin exopigments in liquid and solid media. Melanin synthesis was associated with tyrosinase activity and the enzyme from this strain was isolated and biochemically characterized. Synthetic melanin was then enzymatically produced using the S. cyaneofuscatus Pridham et al. 1958 tyrosinase. As this enzyme showed a higher diphenolase activity, a synthetic melanin from the enzymic oxidation of 3,4-dihydroxyphenylalanine (dopa) was obtained by the use of a Trametes versicolor (L.) Lloyd laccase for comparison. The natural and synthetic pigments were physico-chemically characterized by the use of ultraviolet (UV)-Visible, and Fourier transform infrared (FT-IR) and multifrequency electron paramagnetic resonance (EPR) spectroscopies. All the melanin samples displayed a stable free radical when analyzed by X-band EPR spectroscopy. Once the samples were recorded at Q-band EPR, a copolymer derived from a mixture of different constituents was evident in the natural melanin. All radical species were analyzed and discussed. The use of water-soluble melanin naturally produced by S. cyaneofuscatus Pridham et al. 1958 represents a new biotechnological alternative to commercial insoluble pigments.

Glycans as Regulatory Elements of the Insulin/IGF System: Impact in Cancer Progression.

The insulin/insulin-like growth factor (IGF) system in mammals comprises a dynamic network of proteins that modulate several biological processes such as development, cell growth, metabolism, and aging. Dysregulation of the insulin/IGF system has major implications for several pathological conditions such as diabetes and cancer. Metabolic changes also culminate in aberrant glycosylation, which has been highlighted as a hallmark of cancer. Changes in glycosylation regulate every pathophysiological step of cancer progression including tumour cell-cell dissociation, cell migration, cell signaling and metastasis. This review discusses how the insulin/IGF system integrates with glycosylation alterations and impacts on cell behaviour, metabolism and drug resistance in cancer.

Pressure ulcer dressings in critical patients: a cost analysis.

OBJECTIVE: To assess the direct cost of dressings in pressure ulcer treatment. METHOD: This was a descriptive observational study conducted at an intensive care unit in the Northeast region of Brazil, between November and December 2015. Data were gathered using the Pressure Ulcer Scale for Healing and a form to characterize and assess costs. Values in Brazilian reais (BRL) were converted into U.S. dollars at the exchange rate of USD 0.26/BRL. Univariate and bivariate analyses were conducted. RESULTS: The sample consisted of 15 patients with at least stage 2 ulcers. There was a significant reduction in costs with dressing materials between the initial and final assessments (p=0.002), with a mean of USD 11.9 (±7.4). The most common topical treatments used were essential fatty acids and papain. CONCLUSION: Cost reduction was proportional to the stage of pressure ulcer. The role of nurses in creating evidence-based care plans is crucial to improve care management. OBJETIVO: Avaliar o custo direto com curativos no tratamento de lesões por pressão. MÉTODO: Estudo observacional descritivo, realizado em Unidade de Terapia Intensiva do nordeste do Brasil, de novembro a dezembro de 2015. Foi aplicada a Pressure Ulcer Scale for Healing e formulário para caracterização e avaliação de custos. Os valores da moeda brasileira (R$) foram convertidos para a moeda norte-americana (US$) à taxa de US$0,26/R$. Foram realizadas análises univariadas e bivariadas. RESULTADOS: Compuseram a amostra 15 pacientes com lesões, no mínimo, estágio 2. Houve redução significativa dos custos com materiais de curativos entre as avaliações inicial e final (p=0,002), com média de US$11,9 (±7,4). As terapias tópicas mais frequentes foram ácidos graxos essenciais e papaína. CONCLUSÃO: Verificou-se redução de custos proporcional aos estágios das lesões. Enfatiza-se o papel do enfermeiro na elaboração de planos de cuidados baseados em evidências para melhor gerenciamento do cuidado. OBJETIVO: Evaluar el costo directo de curativos para el tratamiento de lesiones por presión. MÉTODO: Estudio observacional descriptivo en la Unidad de Cuidados Intensivos del noreste de Brasil, de noviembre a diciembre del año 2015. Se aplicó la Pressure Ulcer Scale for Healing y formulario para la caracterización y evaluación de los costos. Los valores de la moneda brasileña (Reales- R$) se convirtieron al dólar estadounidense (US$) a razón de $0.26/R$. Se realizaron análisis univariados y bivariados. RESULTADOS: La muestra consistió en 15 pacientes con lesiones al menos en Etapa 2. Hubo una reducción significativa en el costo de los materiales de curación entre las evaluaciones inicial y final (p=0,002), con un promedio de US$11.9 (±7.4). Los tratamientos tópicos más comunes son los ácidos grasos esenciales y papaína. CONCLUSIÓN: Se verificó una reducción de los costos proporcional a las etapas de las lesiones. Se hace hincapié en el papel de los enfermeros en el desarrollo de planes de cuidados basados en la evidencia, para una mejor gestión de la atención.

Central role of PAFR signalling in ExoU-induced NF-κB activation.

ExoU is an important virulence factor in acute Pseudomonas aeruginosa infections. Here, we unveiled the mechanisms of ExoU-driven NF-κB activation by using human airway cells and mice infected with P. aeruginosa strains. Several approaches showed that PAFR was crucially implicated in the activation of the canonical NF-κB pathway. Confocal microscopy of lungs from infected mice revealed that PAFR-dependent NF-κB activation occurred mainly in respiratory epithelial cells, and reduced p65 nuclear translocation was detected in mice PAFR-/- or treated with the PAFR antagonist WEB 2086. Several evidences showed that ExoU-induced NF-κB activation regulated PAFR expression. First, ExoU increased p65 occupation of PAFR promoter, as assessed by ChIP. Second, luciferase assays in cultures transfected with different plasmid constructs revealed that ExoU promoted p65 binding to the three κB sites in PAFR promoter. Third, treatment of cell cultures with the NF-κB inhibitor Bay 11-7082, or transfection with IκBα negative-dominant, significantly decreased PAFR mRNA. Finally, reduction in PAFR expression was observed in mice treated with Bay 11-7082 or WEB 2086 prior to infection. Together, our data demonstrate that ExoU activates NF-κB by PAFR signalling, which in turns enhances PAFR expression, highlighting an important mechanism of amplification of response to this P. aeruginosa toxin.

Isolation and Characterization of IgM and IgY Antibodies from Plasma of Magellanic Penguins (Spheniscus magellanicus).

Infectious diseases such as aspergillosis, avian malaria, and viral infections are significant threats to the conservation of penguins, leading to morbidity and mortality of these birds both in captivity and in the wild. The immune response to such infectious diseases is dependent on different mechanisms mediated by cells and soluble components such as antibodies. Antibodies or immunoglobulins are glycoproteins that have many structural and functional features that mediate distinct effector immune functions. Three distinct classes of antibodies have been identified in birds: immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin Y (IgY). In this study we aim to establish an efficient laboratory method to obtain IgM and IgY antibodies from plasma samples of healthy adult Magellanic penguins (Spheniscus magellanicus). The protocol was developed combining plasma delipidation, sequential precipitation with caprylic acid and ammonium sulfate, and size-exclusion chromatography. The efficiency of the protocol and the identity of the purified IgM and IgY antibodies were confirmed through enzyme-linked immunosorbent assay, Western blotting, one-dimensional and two-dimensional polyacrylamide gel electrophoresis, and lectin binding assay. Structural and physicochemical properties of IgM and IgY from Magellanic penguins were consistent with those of other avian species. This purification protocol will allow for more detailed studies on the humoral immunity of penguins and for the development of high specificity serologic assays to test Magellanic penguins for infectious pathogens.

Experiences and strategies of people with sickle cell disease in the Federal District: the biographical rupture. / Experiências e estratégias de pessoas com doença falciforme no Distrito Federal: a ruptura biográfica.

This is a study on sickle cell disease, a chronic illness that affects many Brazilians, that aims to understand and analyze how people address the adversities arising from the diagnosis and the biographical rupture. The description of people's experiences and strategies conjures a picture that expresses the respondents' habitus, built in a dialectical relationship with the vulnerability determined by the disease. We adopted a qualitative approach and focused interviews as proposed by Merton, combined with the snowball technique, applied to groups related to sickle cell disease on social networks. Seven participants were selected because they were privileged informants with the disease, were over eighteen, lived in the Federal District, and were non-exclusive users of the Unified Health System. The interview material was categorized from the focal groups employed. The results indicated the following categories: biographical rupture, experience and coping strategies, and healthcare. It is necessary to sensitize professionals and the population about the challenging living conditions of people with sickle cell disease and the consolidation of public policies and care networks to accommodate this population.

Trata-se de um estudo sobre a doença falciforme, enfermidade crônica que afeta muitas pessoas no Brasil. O objetivo foi compreender como as pessoas lidam com as adversidades oriundas do diagnóstico e a ruptura biográfica. A descrição das experiências e estratégias empregadas pelas pessoas compuseram um quadro que expressa os habitus dos entrevistados, construídos em relação dialética com a vulnerabilidade determinada pela doença. A abordagem foi qualitativa e empregou entrevistas focadas como propostas por Merton, a técnica bola de neve aplicada em grupos relacionados à doença falciforme em redes sociais. Sete participantes foram selecionados por serem informantes privilegiados, portadores da doença, maiores de 18 anos, moradores no Distrito Federal e usuários não exclusivos do Sistema Único de Saúde. O material das entrevistas foi categorizado a partir dos núcleos focais empregados. Os resultados apontaram as categorias: ruptura biográfica, experiência e estratégias de enfrentamento, atenção à saúde. Concluímos que é necessária uma sensibilização dos profissionais e da população sobre as dificuldades da condição de vida das pessoas com doença falciforme e a consolidação das políticas públicas e das redes de atendimento para acolher essa população.

Rabies virus circulation in a highly diverse bat assemblage from a high-risk area for zoonoses outbreaks in the Brazilian Amazon.

Bats are the second most diverse order of mammals and play a central role in ecosystem dynamics. They are also important reservoirs of potentially zoonotic microorganisms, of which rabies virus is the most lethal among the bat-transmitted zoonotic pathogens. Importantly, recent outbreaks of human rabies have been reported from the Brazilian Amazon. Here we present a survey of bat species and rabies virus (RABV) circulation in a bat assemblage in the Marajó region, northern Brazil. Using data from mist-net captures and bioacoustic sampling, 56 bat species were recorded along the Jacundá River basin over a 10-day expedition in November 2022. For the investigation of RABV, we used the direct fluorescent antibody test (DFAT) and the rapid fluorescent focus inhibition test (RFFIT). In total, 159 bat individuals from 22 species were investigated for RABV. Five adults of the common vampire bat, Desmodus rotundus, showed RABV-specific antibodies in serum samples. Additionally, we report on local residents with injuries caused by D. rotundus bites and the occurrence of colonies of non-hematophagous bats from different species roosting inside human residences. This scenario raises concerns about the risks of new cases of human rabies and other zoonotic diseases associated with bats in the region and highlights the need for epidemiological surveillance and mitigation measures to prevent outbreaks of emerging infectious diseases.

Herpes simplex type 1 activates glycolysis through engagement of the enzyme 6-phosphofructo-1-kinase (PFK-1).

UNLABELLED: Viruses such as HIV, HCV, Mayaro and HCMV affect cellular metabolic pathways, including glycolysis. Although some studies have suggested that the inhibition of glycolysis affects HSV-1 replication and that HSV-1-infected eyes have increased lactate production, the mechanisms by which HSV-1 induces glycolysis have never been investigated in detail. In this study, we observed an increase in glucose uptake, lactate efflux and ATP content in HSV-1-infected cells. HSV-1 triggered a MOI-dependent increase in the activity of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme of the glycolytic pathway. After HSV-1 infection, we observed increased PFK-1 expression, which increased PFK-1 total activity, and the phosphorylation of this enzyme at serine residues. HSV-1-induced glycolysis was associated with increased ATP content, and these events were critical for viral replication. In summary, our results suggest that HSV-1 triggers glycolysis through a different mechanism than other herpesviruses, such as HCMV. Thus, this study contributes to a better understanding of HSV-1 pathogenesis and provides insights into novel targets for antiviral therapy. HIGHLIGHTS: ►HSV-1 activates glycolysis by PFK-1 activation. ►In HSV-1-infected cells PFK-1 synthesis is up-regulated and phosphorylated at serine residues. ►PFK-1 knockdown impairs HSV-1 replication. ►HSV-1-mediated glycolysis activation increases ATP content.

Species Identification and Mycotoxigenic Potential of Aspergillus Section Flavi Isolated from Maize Marketed in the Metropolitan Region of Asunción, Paraguay.

Zea mays var. amylacea and Zea mays var. indurata are maize ecotypes from Paraguay. Aspergillus section Flavi is the main spoilage fungus of maize under storage conditions. Due to its large intraspecific genetic variability, the accurate identification of this fungal taxonomic group is difficult. In the present study, potential mycotoxigenic strains of Aspergillus section Flavi isolated from Z. mays var. indurata and Z. mays var. amylacea that are marketed in the metropolitan region of Asunción were identified by a polyphasic approach. Based on morphological characters, 211 isolates were confirmed to belong to Aspergillus section Flavi. A subset of 92 strains was identified as Aspergillus flavus by mass spectrometry MALDI-TOF and the strains were classified by MALDI-TOF MS into chemotypes based on their aflatoxins and cyclopiazonic acid production. According to the partial sequencing of ITS and CaM genes, a representative subset of 38 A. flavus strains was confirmed. Overall, 75 A. flavus strains (86%) were characterized as producers of aflatoxins. The co-occurrence of at least two mycotoxins (AF/ZEA, FUM/ZEA, and AF/ZEA/FUM) was detected for five of the Z. mays samples (63%). Considering the high mycological bioburden and mycotoxin contamination, maize marketed in the metropolitan region of Asunción constitutes a potential risk to food safety and public health and requires control measures.

Implementing nursing diagnoses and care for the spiritual dimension of people with cancer: educational actions.

OBJECTIVE: To establish the implementation of nursing diagnoses and care for the spiritual dimension of people with cancer. METHOD: Action research in a university hospital in the north-east of Brazil. Nine nurses and thirteen nursing technicians from the Onco-hematology and Bone Marrow Transplant Unit of this hospital took part. Data collection took place in four phases and involved the talking map technique, pedagogical workshops and a logbook. The groups' speeches were coded using Maxqda software, subjected to Braun and Clarke's thematic analysis and interpreted in the light of Paulo Freire's constructs. RESULTS: Phase 1 sought to apprehend the participants' prior knowledge on the subject; in phase 2, proposals emerged for spiritual care organized in the Nursing Process; in phase 3, the diagnoses and care plan for the spiritual dimension for clinical practice were contemplated; and in phase 4, through the final evaluation, it was possible to see the transformations that occurred in the nursing team's practice with the proposed implementation. CONCLUSION: The educational actions provided significant learning for the nursing team and the implementation of diagnoses and nursing care for the spiritual dimension of people with cancer.

Morbidity survey of the history of snakebites in different communities in the alto Juruá, western Brazilian Amazon.

The Alto Juruá region has a rich diversity of venomous snakes, and snakebites represent an important cause of morbidity. The present study was carried out in five communities in the Alto Juruá region, and aimed to evaluate the history of snakebites in terms of which snakes were involved and what was the victims' conduct in relation to first aid and prevention. Between 2017 and 2019, semi-structured interviews were applied to 260 residents, 56 (21.53%) of whom had a history of snakebites. The profile of the victims is 73.2% male, a resident of rural areas who develops activities mainly in agriculture and extractivism and who has a low level of education. Just over half of the snakebites occurred during the rainy season (52.8%) and the majority during the day (77%). Bothrops bites were the most frequently reported (90.3%) and B. atrox was the most mentioned snake (jararaca and surucucu) for being responsible for snakebites (80.8%). Approximately 87.5% of the bites occurred to the lower limbs, and 48.2% of the victims were barefoot at the time of the bite. Inadequate first-aid procedures were reported, such as using tourniquets and consuming the drink known as "Específico Pessoa", not drinking water, and treatment with traditional therapy (phytotherapics, zootherapeutics and faith healers), as well as not seeking hospital care. Thus, the need to facilitate access to hospital units in these communities and health education (prevention and first aid) are essential in order to minimize this situation.

IL-4 shapes microglia-dependent pruning of the cerebellum during postnatal development.

Interleukin-4 (IL-4) is a type 2 cytokine with pleiotropic functions in adaptive immunity, allergies, and cognitive processes. Here, we show that low levels of IL-4 in the early postnatal stage delineate a critical period in which microglia extensively prune cerebellar neurons. Elevating the levels of this cytokine via peripheral injection, or using a mouse model of allergic asthma, leads to defective pruning, permanent increase in cerebellar granule cells, and circuit alterations. These animals also show a hyperkinetic and impulsive-like phenotype, reminiscent of attention-deficit hyperactivity disorder (ADHD). These alterations are blocked in Il4rαfl/fl::Cx3cr1-CreER mice, which are deficient in IL-4 receptor signaling in microglia. These findings demonstrate a previously unknown role for IL-4 during a neuroimmune critical period of cerebellar maturation and provide a first putative mechanism for the comorbidity between allergic disease and ADHD observed in humans.