Impact of doula's continuous support on serotonin release in parturients: a pilot randomized clinical trial.

Objective: To evaluate whether the continuous support provided by doulas influences the endogenous release of serotonin in parturients. Methods: This pilot study included 24 primigravidae at term. Of these, 12 women received continuous doula support (Experimental Group), whereas the other 12 received the usual assistance without doula support (Control Group). Blood samples were collected from all the women at the active and expulsion stages of labor and at the fourth period of labor (Greenberg period) for evaluation of their serotonin levels using high-performance liquid chromatography. Results: The average serotonin concentrations in the control and experimental groups were respectively 159.33 and 150.02 ng/mL at the active stage, 179.13 and 162.65 ng/mL at the expulsion stage, and 198.94 and 221.21 ng/mL at the Greenberg period. There were no statistically significant differences in serotonin concentrations between the two groups at the active and expulsion stages of labor. By contrast, within the experimental group, a significant increase in serotonin concentration was observed in the Greenberg period compared with the levels in the active and expulsion stages (p < 0.05). Conclusion: The novelty of this study relies on the ability to correlate the influence of the continuous support offered by doulas with the release of serotonin in parturients, with the results suggesting that the assistance received during labor can modulate the levels of hormone release in the Greenberg period. Brazilian Registry of Clinical Trials: RBR-4zjjm4h.

Consumption of interesterified palm oil leads inflammation of white adipose tissue and triggers metabolic disturbances in mice on a high-fat diet.

Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P < 0.05), which was attributed to an increased percentage of fat mass. Plasma concentrations of IL-6, insulin, and HOMA-IR were also elevated in the HFI group. Both the HFP and HFI groups showed hypertrophied adipocytes and pancreatic islets, increased alpha and beta cell masses, hepatic steatosis, low expression of genes related to beta-oxidation, and upregulated lipogenesis. In conclusion, the consumption of interesterified palm oil alters inflammatory and glucose profiles.

Impact of doula's continuous support on serotonin release in parturients: a pilot randomized clinical trial

Abstract Objective: To evaluate whether the continuous support provided by doulas influences the endogenous release of serotonin in parturients. Methods: This pilot study included 24 primigravidae at term. Of these, 12 women received continuous doula support (Experimental Group), whereas the other 12 received the usual assistance without doula support (Control Group). Blood samples were collected from all the women at the active and expulsion stages of labor and at the fourth period of labor (Greenberg period) for evaluation of their serotonin levels using high-performance liquid chromatography. Results: The average serotonin concentrations in the control and experimental groups were respectively 159.33 and 150.02 ng/mL at the active stage, 179.13 and 162.65 ng/mL at the expulsion stage, and 198.94 and 221.21 ng/mL at the Greenberg period. There were no statistically significant differences in serotonin concentrations between the two groups at the active and expulsion stages of labor. By contrast, within the experimental group, a significant increase in serotonin concentration was observed in the Greenberg period compared with the levels in the active and expulsion stages (p < 0.05). Conclusion: The novelty of this study relies on the ability to correlate the influence of the continuous support offered by doulas with the release of serotonin in parturients, with the results suggesting that the assistance received during labor can modulate the levels of hormone release in the Greenberg period. Brazilian Registry of Clinical Trials: RBR-4zjjm4h

ACADEMIC PERFORMANCE OF PHARMACY COURSE STUDENTS IN TWO TEACHING MODELS: TRADITIONAL AND ACTIVE / RENDIMIENTO ACADÉMICO DE ESTUDIANTES DEL CURSO DE FARMACIA EN DOS MODELOS DE ENSEÑANZA: TRADICIONAL Y ACTIVO / DESEMPENHO ACADÊMICO DE ESTUDANTES DO CURSO DE FARMÁCIA EM DOIS MODELOS DE ENSINO: TRADICIONAL E ATIVO

The National Curriculum Guidelines of the Pharmacy Undergraduation Course are structured by the development of competences in the teaching-learning process. This study brings as a guiding question which learning methodology contributes to better academic rates and better student performance? This exploratory study, with a quantitative approach and with a documentary design, compiled information about the academic indexes of students in the Pharmacy course at XXX, from 2015 to 2019, in the two learning models: active (AL) and traditional (TL) . A total of 357 undergraduates were documented, with 115 students completing their training in AL and 242 in TL, with a predominance of women (76.19%), aged between 20 and 30 years (64.43%). In terms of completion time, AL students had a shorter completion time, while TL students had better individual performance indices (p<0.002), and the course average (CA) of both models above 7 points. Regarding the academic indicators per course, the retention rates were AL (4.8%) and TL (15.5%), AL (13.1%), and TL (5.48%) dropout rates, AL (44.44%) and TL success rates (50.65%). Regarding the performance of students in the ENADE, both for general and specific training, AL and TL had averages higher than the national average, with concept 4 for both learning models. More detailed studies are needed to support the pedagogical and administrative management of Pharmacy courses offered in public undergraduate education institutions.

Las Directrices Curriculares Nacionales de la Carrera de Graduación en Farmacia están estructuradas por el desarrollo de competencias en el proceso de enseñanza-aprendizaje. Este estudio trae como pregunta orientadora ¿qué metodología de aprendizaje contribuye a mejores índices académicos y mejor desempeño de los estudiantes? Este estudio exploratorio, con enfoque cuantitativo y con diseño documental, recopiló información sobre los índices académicos de los estudiantes de la carrera de Farmacia de la XXX, de 2015 a 2019, en los dos modelos de aprendizaje: activo (AL) y tradicional (TL) . Se documentaron un total de 357 estudiantes de pregrado, con 115 estudiantes completando su formación en AL y 242 en TL, con predominio de mujeres (76,19%), con edades entre 20 y 30 años (64,43%). En cuanto al tiempo de finalización, los alumnos de AL tuvieron un tiempo de finalización más corto, mientras que los alumnos de TL tuvieron mejores índices de desempeño individual (p<0.002), y el promedio del curso (CA) de ambos modelos por encima de los 7 puntos. En cuanto a los indicadores académicos por curso, las tasas de retención fueron AL (4,8%) y TL (15,5%), AL (13,1%) y TL (5,48%), tasas de deserción, AL (44,44%) y TL tasas de éxito (50,65%). ). En cuanto al desempeño de los estudiantes en la ENADE, tanto para formación general como específica, AL y TL tuvieron promedios superiores a la media nacional, con concepto 4 para ambos modelos de aprendizaje. Son necesarios estudios más detallados que apoyen la gestión pedagógica y administrativa de las carreras de Farmacia que se ofrecen en las instituciones públicas de educación de pregrado.

As Diretrizes Curriculares Nacionais (DCN's) do Curso de Graduação Farmácia estão estruturadas pelo desenvolvimento de competências no processo de ensino-aprendizagem. Este estudo traz como questão norteadora qual metodologia de ensino contribui para melhores índices acadêmicos e melhor desempenho estudantil? Este estudo de caráter exploratório, de abordagem quantitativa e com delineamento documental compilou informações acerca dos índices acadêmicos dos estudantes do curso de Farmácia da XXX, no período de 2015 a 2019, nos dois modelos de ensino: ativo (MA) e tradicional (MT). Foram documentados 357 concludentes, sendo 115 estudantes concluíram sua formação em MA e 242 em MT, com predominância do sexo feminino (76,19%), faixa etária entre 20 e 30 anos (64,43%). No quesito tempo de conclusão, estudantes em MA apresentaram menor tempo de conclusão, ao passo que estudantes do MT obtiveram melhores índices de desempenho individual (p<0,002), e a média de curso (MC) de ambos modelos acima de 7. Em relação aos indicadores acadêmicos por curso, as taxas de retenção foram MA (4,8%) e MT (15,5%), taxas de evasão MA (13,1%), e MT (5,48%), taxas de sucesso MA (44,44%) e MT (50,65%). Em relação ao desempenho dos estudantes no ENADE, tanto para formação geral quanto específica, MA e MT apresentaram médias superiores à média nacional, com conceito 4 para ambos modelos de ensino. São necessários estudos mais detalhados para subsidiar gerenciamento pedagógico e administrativo dos cursos de Farmácia ofertados nas instituições de ensino superior públicas.

Vitamin D modulates cortical transcriptome and behavioral phenotypes in an Mecp2 heterozygous Rett syndrome mouse model.

Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the transcriptional regulator MECP2. Mecp2 loss-of-function leads to the disruption of many cellular pathways, including aberrant activation of the NF-κB pathway. Genetically attenuating the NF-κB pathway in Mecp2-null mice ameliorates hallmark phenotypes of RTT, including reduced dendritic complexity, raising the question of whether NF-κB pathway inhibitors could provide a therapeutic avenue for RTT. Vitamin D is a known inhibitor of NF-κB signaling; further, vitamin D deficiency is prevalent in RTT patients and male Mecp2-null mice. We previously demonstrated that vitamin D rescues the aberrant NF-κB activity and reduced neurite outgrowth of Mecp2-knockdown cortical neurons in vitro, and that dietary vitamin D supplementation rescues decreased dendritic complexity and soma size of neocortical projection neurons in both male hemizygous Mecp2-null and female heterozygous mice in vivo. Here, we have identified over 200 genes whose dysregulated expression in the Mecp2+/- cortex is modulated by dietary vitamin D. Genes normalized with vitamin D supplementation are involved in dendritic complexity, synapses, and neuronal projections, suggesting that the rescue of their expression could underpin the rescue of neuronal morphology. Further, there is a disruption in the homeostasis of the vitamin D synthesis pathway in Mecp2+/- mice, and motor and anxiety-like behavioral phenotypes in Mecp2+/- mice correlate with circulating vitamin D levels. Thus, our data indicate that vitamin D modulates RTT pathology and its supplementation could provide a simple and cost-effective partial therapeutic for RTT.

The Potential Role of Previous Physical Exercise Program to Reduce Seizure Susceptibility: A Systematic Review and Meta-Analysis of Animal Studies.

Background: Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical exercise programs. In contrast to the influence of exercise after epilepsy previously established, various studies have been conducted attempting to investigate whether physical activity reduces brain susceptibility to seizures or prevents epilepsy. We report a systematic review and meta-analysis of different animal models that addressed the impact of previous physical exercise programs to reduce seizure susceptibility. Methods: We included animal model (rats and mice) studies before brain insult that reported physical exercise programs compared with other interventions (sham, control, or naïve). We excluded studies that investigated animal models after brain insult, associated with supplement nutrition or drugs, that did not address epilepsy or seizure susceptibility, ex vivo studies, in vitro studies, studies in humans, or in silico studies. Electronic searches were performed in the MEDLINE (PubMed), Web of Science (WOS), Scopus, PsycINFO, Scientific Electronic Library Online (SciELO) databases, and gray literature, without restrictions to the year or language of publication. We used SYRCLE's risk of bias tool and CAMARADES checklist for study quality. We performed a synthesis of results for different types of exercise and susceptibility to seizures by random-effects meta-analysis. Results: Fifteen studies were included in the final analysis (543 animals), 13 of them used male animals, and Wistar rats were the most commonly studied species used in the studies (355 animals). The chemoconvulsants used in the selected studies were pentylenetetrazol, penicillin, kainic acid, pilocarpine, and homocysteine. We assessed the impact of study design characteristics and the reporting of mitigations to reduce the risk of bias. We calculated a standardized mean difference effect size for each comparison and performed a random-effects meta-analysis. The meta-analysis included behavioral analysis (latency to seizure onset, n = 6 and intensity of motor signals, n = 3) and electrophysiological analysis (spikes/min, n = 4, and amplitude, n = 6). The overall effect size observed in physical exercise compared to controls for latency to seizure onset was -130.98 [95% CI: -203.47, -58.49] (seconds) and the intensity of motor signals was -0.40 [95% CI: -1.19, 0.40] (on a scale from 0 to 5). The largest effects were observed in electrophysiological analysis for spikes/min with -26.96 [95% CI: -39.56, -14.36], and for spike amplitude (µV) with -282.64 [95% CI: -466.81, -98.47]. Discussion: Limitations of evidence. A higher number of animal models should be employed for analyzing the influence of exerciseon seizure susceptibility. The high heterogeneity in our meta-analysis is attributable to various factors, including the number of animals used in each study and the limited number of similar studies. Interpretation. Studies selected in this systematic review and meta-analysis suggest that previous physical exercise programs can reduce some of the main features related to seizure susceptibility [latency seizure onset, spikes/min, and spike amplitude (µV)] induced by the administration of different chemoconvulsants. Systematic Review Registration: PROSPERO, identifier CRD42021251949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251949.

BEWO trophoblast cells and Toxoplasma gondii infection modulate cell death mechanisms in THP-1 monocyte cells by interference in the expression of death receptor and intracellular proteins.

Crosstalk between trophoblast and monocytes is essential for gestational success, and it can be compromised in congenital toxoplasmosis. Cell death is one of the mechanisms involved in the maintenance of pregnancy, and this study aimed to evaluate the role of trophoblast in the modulation of monocyte cell death in the presence or absence of Toxoplasma gondii infection. THP-1 cells were stimulated with supernatants of BeWo cells and then infected or not with T. gondii. The supernatants were collected and analyzed for the secretion of human Fas ligand, and cells were used to determine cell death and apoptosis, cell death receptor, and intracellular proteins expression. Cell death and apoptosis index were higher in uninfected THP-1 cells stimulated with supernatants of BeWo cells; however, apoptosis index was reduced by T. gondii infection. Macrophage migration inhibitory factor (MIF) and transforming growth factor (TGF)-ß1, secreted by BeWo cells, altered the cell death and apoptosis rates in THP-1 cells. In infected THP-1 cells, the expression of Fas/CD95 and secretion of FasL was significantly higher; however, caspase 3 and phosphorylated extracellular-signal-regulated kinase (ERK1/2) were downregulated. Results suggest that soluble factors secreted by BeWo cells induce cell death and apoptosis in THP-1 cells, and Fas/CD95 can be involved in this process. On the other hand, T. gondii interferes in the mechanism of cell death and inhibits THP-1 cell apoptosis, which can be associated with active caspase 3 and phosphorylated ERK1/2. In conclusion, our results showed that human BeWo trophoblast cells and T. gondii infection modulate cell death in human THP-1 monocyte cells.

ERK1/2 phosphorylation and IL-6 production are involved in the differential susceptibility to Toxoplasma gondii infection in three types of human (cyto/ syncytio/ extravillous) trophoblast cells.

During pregnancy, Toxoplasma gondii can triggers serious manifestations and potentially affect the fetal development. In this scenario, differences in susceptibility of trophoblast cells to T. gondii infection might be evaluated in order to establish new therapeutic approaches capable of interfering in the control of fetal infection by T. gondii. This study aimed to evaluate the susceptibility of cytotrophoblast, syncytiotrophoblast and extravillous trophoblast cells to T. gondii infection. Our data demonstrate that HTR-8/SVneo cells (extravillous trophoblast cells) present higher susceptibility to T. gondii infection when compared to syncytiotrophoblast and cytotrophoblast cells, whereas syncytiotrophoblast was the cell type more resistant to the parasite infection. Also, cytotrophoblast and syncytiotrophoblast cells produced significantly more IL-6 than HTR-8/SVneo cells. On the other hand, HTR-8/SVneo cells showed higher ERK1/2 phosphorylation than cytotrophoblast and syncytiotrophoblast cells. ERK1/2 inhibition reduced T. gondii infection and increased IL-6 production in HTR-8/SVneo cells. Thus, it is plausible to conclude that the greater susceptibility of HTR-8/SVneo cells to infection by T. gondii is related to a higher ERK1/2 phosphorylation and lower levels of IL-6 in these cells compared to other cells, suggesting that these mediators may be important to favor the parasite infection in this type of trophoblastic population.

Intervention bimanual stimulates the abilities in infants with asymmetry / A intervenção bimanual estimula as habilidades em bebês com assimetria

Abstract Introduction: The cerebral palsy and brachial plexus injury may cause asymmetry in the use of the upper limbs (UL). This condition requires early treatment to reduce the impact of the child's life; therefore, several proposed interventions aim to increase their functional independence. The Constraint-Induced Movement Therapy (CIMT) and Hand-Arm Bimanual Intensive Therapy (HABIT) have been widely considered effective interventions to improve hand function. Objective: Investigate the effects of an intervention protocol based on the CIMT and HABIT theoretical foundations in the stimulation of manual function in infants with the UL asymmetry. Methods: Five infants (6-24 months) participated in the study. To evaluate the motor function of infants we used Pediatric Motor Activity Log (PMAL-R) and Manual Function Evaluation (AMIGO), and to assess the caregiver's perception of the participation of the infant in daily tasks, we used the Pediatric Disability Assessment Inventory (PEDI). All evaluations occurred before, immediately after the intervention, and after four months for follow-up recording, and were analyzed descriptively by Jacobson- Truax method. Results: The results between evaluation and reevaluation demonstrated evolution in all aspects studied. In the PEDI self-care session, an average of 38.6 (±8.4) - 44.2 (±7.4); PEDI Mobility: 28.8 (±20.3) - 36.28 (±21.7); PEDI Social Function: 40.1 (±10.2) - 42.3 (±8.9). The PMAL-R quantity and quality results evidence a highly positive clinical significance in all infants. Conclusion: The application of the modified restriction intervention protocol resulted in reliable and clinically significant changes in all cases.

Resumo Introdução: A paralisia cerebral e a lesão do plexo braquial podem causar assimetria no uso dos membros superiores (MS). Esta condição requer tratamento precoce para reduzir o impacto na vida do indivíduo, portanto várias intervenções têm sido propostas com o objetivo final de aumentar sua independência funcional. A terapia de movimento induzido por restrição (CIMT) e a terapia intensiva bimanual de mão-braço (HABIT) têm sido amplamente eficazes para aumentar a função da mão. Objetivo: Investigar os efeitos de um protocolo de intervenção beseado nos fundamentos teóricos da CIMT e do HABIT, na estimulação da função manual em bebês com assimetria de MS. Métodos: Cinco crianças (6-24 meses) participaram do estudo. Para avaliar a função motora dos lactentes foram utilizados o Pediatric Motor Activity Log (PMAL) e a Avaliação de Função Manual (AMIGO); o Pediatric Disability Assessment Inventory (PEDI) foi aplicado aos cuidadores, a fim de avaliar sua percepção da participação funcional do lactente nas tarefas diárias. Todas as avaliações ocorreram antes, imediatamente após a intervenção e após quatro meses para registro de acompanhamento. Os dados foram analisados descritivamente pelo método de Jacobson-Truax. Resultados: Os resultados entre avaliação e reavaliação demonstraram evolução em todos os aspectos estudados. Na sessão de autocuidado do PEDI, a média de 38,6 (±8,4) foi para 44,2 (±7,4); PEDI - Mobilidade: de 28,8 (±20,3) a 36,28 (±21,7); PEDI - Função Social: de 40,1 (±10,2) a 42,3 (±8,9). Os resultados de quantidade e qualidade do PMAL-R evidenciam um significado clínico altamente positivo em todos os bebês. Conclusão: A aplicação do protocolo de intervenção de restrição modificado resultou em alterações confiáveis e clinicamente significativas em todos os casos.

Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection.

Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF-/-) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF-/- mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF-/- mice. We also detected that the Th2/Treg response was more pronounced in MIF-/- mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment.

Adaptation and preliminary validation of the genetic counseling outcome scale (GCOS-24) in a Brazilian genetic counseling setting.

Health professionals working in services providing genetic counseling need objective instruments to assess genetic counseling outcomes and also to "give a voice" to those using these services. Lack of knowledge regarding such outcomes may directly impact the effectiveness and the potential benefits of counseling, quality of life, health promotion, and empowerment of those receiving counseling. There are very few instruments available for most countries, however there are none in Brazil. In this context, this study aimed to adapt and preliminarily validate the Genetic Counseling Outcome Scale (GCOS-24), a Patient-Reported Outcome Measure (PROM), originally developed in British English. This methodological study recruited 278 individuals attending a medical genetic service at a Brazilian university hospital. We performed the translation, back-translation, semantic validation, pilot study and field study for testing of some psychometric properties. The instrument's internal consistency and test-retest reliability (stability) were assessed using Cronbach's alpha coefficient and Intraclass Correlation Coefficient, respectively. The Brazilian version of the GCOS-24 presented face and content validity, satisfactory internal consistency (Cronbach's α = 0.71), and moderate stability (ICC = 0.52). It was considered reliable, easily understood and relevant to assessing the genetic counseling outcomes for the study participants. Its construct validity still needs to be assessed to verify the instrument's internal structure and its potential use to measure change in empowerment following genetic counseling provided by Brazilian clinical genetics services.

Vitamin D Supplementation Rescues Aberrant NF-κB Pathway Activation and Partially Ameliorates Rett Syndrome Phenotypes in Mecp2 Mutant Mice.

Rett syndrome (RTT) is a severe, progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MECP2 We previously identified aberrant NF-κB pathway upregulation in brains of Mecp2-null mice and demonstrated that genetically attenuating NF-κB rescues some characteristic neuronal RTT phenotypes. These results raised the intriguing question of whether NF-κB pathway inhibitors might provide a therapeutic avenue in RTT. Here, we investigate whether the known NF-κB pathway inhibitor vitamin D ameliorates neuronal phenotypes in Mecp2-mutant mice. Vitamin D deficiency is prevalent among RTT patients, and we find that Mecp2-null mice similarly have significantly reduced 25(OH)D serum levels compared with wild-type littermates. We identify that vitamin D rescues aberrant NF-κB pathway activation and reduced neurite outgrowth of Mecp2 knock-down cortical neurons in vitro Further, dietary supplementation with vitamin D in early symptomatic male Mecp2 hemizygous null and female Mecp2 heterozygous mice ameliorates reduced neocortical dendritic morphology and soma size phenotypes and modestly improves reduced lifespan of Mecp2-nulls. These results elucidate fundamental neurobiology of RTT and provide foundation that NF-κB pathway inhibition might be a therapeutic target for RTT.

Sex differences in Mecp2-mutant Rett syndrome model mice and the impact of cellular mosaicism in phenotype development.

There is currently no effective treatment for Rett syndrome (RTT), a severe X-linked progressive neurodevelopmental disorder caused by mutations in the transcriptional regulator MECP2. Because MECP2 is subjected to X-inactivation, most affected individuals are female heterozygotes who display cellular mosaicism for normal and mutant MECP2. Males who are hemizygous for mutant MECP2 are more severely affected than heterozygous females and rarely survive. Mecp2 loss-of-function is less severe in mice, however, and male hemizygous null mice not only survive until adulthood, they have been the most commonly studied model system. Although heterozygous female mice better recapitulate human RTT, they have not been as thoroughly characterized. This is likely because of the added experimental challenges that they present, including delayed and more variable phenotypic progression and cellular mosaicism due to X-inactivation. In this review, we compare phenotypes of Mecp2 heterozygous female mice and male hemizygous null mouse models. Further, we discuss the complexities that arise from the many cell-type and tissue-type specific roles of MeCP2, as well as the combination of cell-autonomous and non-cell-autonomous disruptions that result from Mecp2 loss-of-function. This is of particular importance in the context of the female heterozygous brain, composed of a mixture of MeCP2+ and MeCP2- cells, the ratio of which can alter RTT phenotypes in the case of skewed X-inactivation. The goal of this review is to provide a clearer understanding of the pathophysiological differences between the mouse models, which is an essential consideration in the design of future pre-clinical studies.

Erratum to "Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection" [Cytokine: X 2 (2020) 100034].

[This corrects the article DOI: 10.1016/j.cytox.2020.100034.].

Biogenic Silver Nanoparticles Can Control Toxoplasma gondii Infection in Both Human Trophoblast Cells and Villous Explants.

The combination of sulfadiazine and pyrimethamine plus folinic acid is the conventional treatment for congenital toxoplasmosis. However, this classical treatment presents teratogenic effects and bone marrow suppression. In this sense, new therapeutic strategies are necessary to reduce these effects and improve the control of infection. In this context, biogenic silver nanoparticles (AgNp-Bio) appear as a promising alternative since they have antimicrobial, antiviral, and antiparasitic activity. The purpose of this study to investigate the action of AgNp-Bio in BeWo cells, HTR-8/SVneo cells and villous explants and its effects against Toxoplasma gondii infection. Both cells and villous explants were treated with different concentrations of AgNp-Bio or combination of sulfadiazine + pyrimethamine (SDZ + PYZ) in order to verify the viability. After, cells and villi were infected and treated with AgNp-Bio or SDZ + PYZ in different concentrations to ascertain the parasite proliferation and cytokine production profile. AgNp-Bio treatment did not reduce the cell viability and villous explants. Significant reduction was observed in parasite replication in both cells and villous explants treated with silver nanoparticles and classical treatment. The AgNp-Bio treatment increased of IL-4 and IL-10 by BeWo cells, while HTR8/SVneo cells produced macrophage migration inhibitory factor (MIF) and IL-4. In the presence of T. gondii, the treatment induced high levels of MIF production by BeWo cells and IL-6 by HTR8SV/neo. In villous explants, the AgNp-Bio treatment downregulated production of IL-4, IL-6, and IL-8 after infection. In conclusion, AgNp-Bio can decrease T. gondii infection in trophoblast cells and villous explants. Therefore, this treatment demonstrated the ability to reduce the T. gondii proliferation with induction of inflammatory mediators in the cells and independent of mediators in chorionic villus which we consider the use of AgNp-Bio promising in the treatment of toxoplasmosis in BeWo and HTR8/SVneo cell models and in chorionic villi.

Construction and reconstruction of brain circuits: normal and pathological axon guidance.

Perception of our environment entirely depends on the close interaction between the central and peripheral nervous system. In order to communicate each other, both systems must develop in parallel and in coordination. During development, axonal projections from the CNS as well as the PNS must extend over large distances to reach their appropriate target cells. To do so, they read and follow a series of axon guidance molecules. Interestingly, while these molecules play critical roles in guiding developing axons, they have also been shown to be critical in other major neurodevelopmental processes, such as the migration of cortical progenitors. Currently, a major hurdle for brain repair after injury or neurodegeneration is the absence of axonal regeneration in the mammalian CNS. By contrasts, PNS axons can regenerate. Many hypotheses have been put forward to explain this paradox but recent studies suggest that hacking neurodevelopmental mechanisms may be the key to promote CNS regeneration. Here we provide a seminar report written by trainees attending the second Flagship school held in Alpbach, Austria in September 2018 organized by the International Society for Neurochemistry (ISN) together with the Journal of Neurochemistry (JCN). This advanced school has brought together leaders in the fields of neurodevelopment and regeneration in order to discuss major keystones and future challenges in these respective fields.

Purified glycerin in balanced diets for chicken broilers from 8 to 21 days old / Glicerina purificada em dietas balanceadas para frangos de corte dos 8 aos 21 dias de idade

This paper aimed to evaluate the metabolizability, performance and economic viability of purified glycerin inclusion in balanced diets fed to chicken broilers from 8 to 21 days old. Two experiments were conducted. In the first experiment, 100 broilers (14 days old) were distributed in a completely randomized design into two treatments, with five replications of 10 broilers. Treatments consisted of a control diet and a test diet, in which purified glycerin replaced 10% of the control diet. In the second experiment, 200 broilers (8 days old) were distributed in a completely randomized design into four treatments (0, 2, 4 and 6% of purified glycerin inclusion), with five replications of 10 broilers. The weight gain, feed intake, feed conversion, final weight, apparent metabolizable energy (AME), nitrogen-corrected apparent metabolizable energy (AMEn), metabolizability coefficients of dry matter (DMMC), crude protein (CPMC) and gross energy (GEMC), and the cost of feed per kg of broiler produced were evaluated. The AME, AMEn, DMMC, CPMC and GEMC from the purified glycerin were 3790 and 3560 kcal/kg, and 83.72, 71.52 and 86.27%, respectively. The glycerin levels did not affect (p>0.05) any of the performance characteristics (weight gain, feed intake, feed conversion and final weight). The lowest feeding cost and the highest gross margin were obtained for broilers fed with 6% purified glycerin. The inclusion of 6% purified glycerin in balanced diets for broilers from 8 to 21 days old was technically and economically feasible.

Objetivou-se neste trabalho avaliar a metabolizabilidade, o desempenho zootécnico e a viabilidade econômica da inclusão de glicerina purificada, em dietas balanceadas para frangos de corte dos 8 aos 21 dias de idade. Foram realizados dois experimentos, sendo que, no primeiro experimento, foram utilizados 100 pintos de 14 dias de idade, distribuídos em delineamento inteiramente casualizado (DIC), com dois tratamentos, cinco repetições de 10 aves. Os tratamentos consistiram de uma dieta referência e uma dieta teste, na qual a glicerina purificada substituiu 10% da dieta referência. No segundo experimento, foram utilizados 200 pintos de 8 dias de idade, distribuídos em delineamento experimental inteiramente casualizado (DIC), com quatro tratamentos (0, 2, 4 e 6% de inclusão de glicerina purificada) e cinco repetições de 10 aves. Foram determinados o ganho de peso, consumo de ração, conversão alimentar, peso final, energia metabolizável aparente (EMA), energia metabolizável aparente corrigida pelo balanço de nitrogênio (EMAn), os coeficientes de metabolizabilidade da matéria seca (CMMS), proteína bruta (CMPB), energia bruta (CMEB) e o custo da alimentação por kg de frango produzido. A EMA, EMAn e os CMMS, CMPB, CMEB da glicerina purificada obtida foram de 3790, 3560 Kcal/kg e 83,72, 71,52, 86,27%, respectivamente. Observou-se que a inclusão de glicerina purificada não afetou (p>0,05) o desempenho (ganho de peso, consumo de ração, conversão alimentar e peso final). O menor custo com a alimentação e a maior margem bruta foi obtido com os frangos alimentados com 6% de inclusão de glicerina purificada. A inclusão de 6% de glicerina purificada em dietas balanceadas para frangos de corte dos 8 aos 21 dias de idade, mostrou-se técnica e economicamente viável.

Evaluation of the autonomic nervous system by analysis of heart rate variability in the preterm infants.

BACKGROUND: Premature infants may present with damage to the autonomic nervous system (ANS), which may be related to poorer neurological development. Among the techniques used to evaluate the ANS, heart rate variability (HRV) emerged as a simple, non-invasive, and easy to apply tool. The aim of the present study was to analyze and compare HRV in preterm infants at different times of hospitalization in order to verify the possible environmental relationships or clinical evolution with HRV. METHODS: A longitudinal, prospective, and descriptive study with non-probabilistic sampling composed of 25 collections of preterm infants of HRV at two moments: moment I (within 15 days of birth) and moment II (after 45 days post-birth). The Polar V800 heart rate monitor was used with the Polar H10 cardiac transducer to collect HRV, which was collected in the supine position for 15 min. The HRV data were analyzed by the linear method in frequency domain and time domain and by the nonlinear method using Kubios HRV analysis software, version 3.0.2. RESULTS: There was an increase in HRV values at moment II, these being statistically significant in the SD1, ApEn, and SampEn. Data related to increased sympathetic nervous system activity, parasympathetic nervous system activity, and increased index complexity. CONCLUSIONS: The data demonstrate an increase in HRV values in premature infants at moment II, demonstrating a possible development in the maturation of the ANS during hospitalization. TRIAL REGISTRATION: RBR-3x7gz8 retrospectively registered.

Increased Toxoplasma gondii Intracellular Proliferation in Human Extravillous Trophoblast Cells (HTR8/SVneo Line) Is Sequentially Triggered by MIF, ERK1/2, and COX-2.

Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine, which mediates the regulation of diverse cellular functions. It is produced by extravillous trophoblastic cells and has been found to be involved in the pathogenesis of diseases caused by some protozoa, including Toxoplasma gondii. Previous studies demonstrated the ability of T. gondii to take advantage of MIF action in human trophoblast cells. However, MIF action in T. gondii-infected extravillous trophoblastic cells (HTR8/SVneo cell line) has not been fully investigated. The present study aimed to investigate the role of MIF in T. gondii-infected HTR8/SVneo cells and verify the intracellular signaling pathways triggered by this cytokine. We found that T. gondii increased MIF production by HTR8/SVneo cells, and by contrast, MIF inhibition, by ISO-1, led to a significant decrease in T. gondii proliferation and CD74 expression in HTR8/SVneo cells. Moreover, in infected HTR8/SVneo cells, the addition of recombinant MIF (rMIF) increased CD44 co-receptor expression, ERK1/2 phosphorylation, COX-2 expression, and IL-8 production, which favored T. gondii proliferation. Our findings indicate that T. gondii can use MIF to modulate important factors in HTR8/SVneo cells, being a possible explanation for the higher susceptibility of extravillous trophoblast cells than other trophoblast cell populations.