Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability

The development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a lack of understanding of how their combined effect may impact vulnerability to drug abuse in adolescence. The present study used rats with different vulnerability to depression (Wistar and Wistar-Kyoto) to investigate the impact of maternal separation (MS) on emotional state and drug addiction vulnerability during the adolescence period. Mothers and their litters were subjected to MS (180 min/day) from postnatal day 2 to 14. The offspring emotional state was assessed by observing their exploratory behavior. Drug abuse vulnerability was assessed through conditioning to cocaine. MS impacted the emotional state in both strains. Wistar responded with increased exploration, while Wistar-Kyoto increased anxiety-like behaviours. Despite the different coping strategies displayed by the two strains when challenged with the behavioural tests, drug conditioning was equally impacted by MS in both strains. Early-life stress appears to affect drug abuse vulnerability in adolescence independently of a depression background, suggesting emotional state as the main driving risk factor.info:eu-repo/semantics/publishedVersio

Maternal stress and vulnerability to depression: coping and maternal care strategies and its consequences on adolescent offspring

Depressive mothers often find mother-child interaction to be challenging. Maternal stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to depressive-like behavior (Wistar and Kyoto) to investigate the impact of stress (maternal separation-MS) on maternal behavior and adolescent offspring cognition. MS in Kyoto dams increased pup-contact, resulting in higher oxytocin levels and lower anxiety-like behavior after weaning, while worsening their adolescent offspring cognitive behavior. Whereas MS in Wistar dams elicited higher quality of pup-directed behavior, increasing brain-derived neurotrophic factor (BDNF) in the offspring, which seems to have prevented a negative impact on cognition. Hypothalamic oxytocin seems to affect the salience of the social environment cues (negatively for Kyoto) leading to different coping strategies. Our findings highlight the importance of contextual and individual factors in the understanding of the oxytocin role in modulating maternal behavior and stress regulatory processes.info:eu-repo/semantics/publishedVersio

Leukocyte and lymphoid organ ontogeny

Autoimmune regulator+ (Aire) medullary thymic epithelial cells (mTECs) play a critical role in tolerance induction. Several studies demonstrated that Aire+mTECs differentiate further into Post-Aire cells. Yet, the identification of terminal stages of mTEC maturation depends on unique fate-mapping mouse models. Herein, we resolve this limitation by segmenting the mTEChi(MHCIIhiCD80hi) compartment into mTECA/hi (CD24−Sca1−), mTECB/hi (CD24+Sca1−), and mTECC/hi (CD24+Sca1+). While mTECA/hi included mostly Aire-expressing cells, mTECB/hi contained Aire+ and Aire− cells and mTECC/hi were mainly composed of cells lacking Aire. The differential expression pattern of Aire led us to investigate the precursor-product relationship between these subsets. Strikingly, transcriptomic analysis of mTECA/hi, mTECB/hi, and mTECC/hi sequentially mirrored the specific genetic program of Early-, Late- and Post-Aire mTECs. Corroborating their Post-Aire nature, mTECC/hi downregulated the expression of tissue-restricted antigens, acquired traits of differentiated keratinocytes, and were absent in Aire-deficient mice. Collectively, our findings reveal a new and simple blueprint to survey late stages of mTEC differentiation

Dinâmicas socioecológicas no semiárido baiano a partir do acesso a água : O caso da família Farias

A dinâmica socioecológica dos camponeses do semiárido brasileiro vem mudando há algumas décadas em decorrência do acesso a programas e políticas públicas para a convivência com o semiárido. Este trabalho apresenta o resultado da avaliação socioecológica em um agroecossistema no semiárido baiano após o acesso a tecnologias de captação e armazenamento de água da chuva, visando contribuir com a discussão sobre a sustentabilidade de agroecossistemas no semiárido brasileiro. Para construção desses dados foram utilizadas as metodologias e ferramentas de um Diagnóstico Rural Participativo. As tecnologias de captação e armazenamento de água da chuva possibilitaram mudanças significativas na vida dessas famílias, permitindo o acesso além da água para consumo humano e ampliando esse acesso para a água de produção, permitindo o cultivo de espécies e a criação de animais que garantem a manutenção da família no tempo e no espaço.The socioecological dynamics of the Brazilian semi-arid farmers has changed a few decades as a result of access to programs and policies for coexistence with the semiarid region. This paper presents the results of socio-ecological evaluation in a semi-arid agroecosystem in Bahia after access to rainwater capture and storage technologies, to contribute to the discussion about the sustainability of agro-ecosystems in the Brazilian semiarid region. Construction of such data the methodologies and tools of a Participatory Rural Appraisal. The capture and rainwater storage technologies enabled significant changes in the lives of these families, allowing access in addition to drinking water and expanding such access for the production of water, allowing the cultivation of species and breeding that guarantee family maintenance in time and space.Eje A6: Desarrollo Rural, Movimientos Sociales, Estado y AgroecologíaFacultad de Ciencias Agrarias y Forestale

Dinâmicas socioecológicas no semiárido baiano a partir do acesso a água : O caso da família Farias

A dinâmica socioecológica dos camponeses do semiárido brasileiro vem mudando há algumas décadas em decorrência do acesso a programas e políticas públicas para a convivência com o semiárido. Este trabalho apresenta o resultado da avaliação socioecológica em um agroecossistema no semiárido baiano após o acesso a tecnologias de captação e armazenamento de água da chuva, visando contribuir com a discussão sobre a sustentabilidade de agroecossistemas no semiárido brasileiro. Para construção desses dados foram utilizadas as metodologias e ferramentas de um Diagnóstico Rural Participativo. As tecnologias de captação e armazenamento de água da chuva possibilitaram mudanças significativas na vida dessas famílias, permitindo o acesso além da água para consumo humano e ampliando esse acesso para a água de produção, permitindo o cultivo de espécies e a criação de animais que garantem a manutenção da família no tempo e no espaço.The socioecological dynamics of the Brazilian semi-arid farmers has changed a few decades as a result of access to programs and policies for coexistence with the semiarid region. This paper presents the results of socio-ecological evaluation in a semi-arid agroecosystem in Bahia after access to rainwater capture and storage technologies, to contribute to the discussion about the sustainability of agro-ecosystems in the Brazilian semiarid region. Construction of such data the methodologies and tools of a Participatory Rural Appraisal. The capture and rainwater storage technologies enabled significant changes in the lives of these families, allowing access in addition to drinking water and expanding such access for the production of water, allowing the cultivation of species and breeding that guarantee family maintenance in time and space.Eje A6: Desarrollo Rural, Movimientos Sociales, Estado y AgroecologíaFacultad de Ciencias Agrarias y Forestale

METHYLPHENIDATE: PROCONVULSANT EFFECT AND ACTION ON ACETYL CHOLINESTERASE ACTIVITY IN YOUNG AND ADULT MICE

Objective: Methylphenidate (MPH) is a derivative of piperidine, structurally related to amphetamine. It is the most widely psychostimulant used in Brazil for treating attention deficit disorder and hyperactivity. This drug was investigated in an epilepsy model induced by pilocarpine and on acetylcholinesterase (AChE) activity in young and adult mice. Methods: The control group was treated with saline. The treated groups received MPH (2.5, 5, 10 or 20 mg/kg) in single dose, followed by pilocarpine (400mg/Kg). The groups were observed for1h after treatment. Results: MPH, in all doses, was efficacious in decreasing both the latency to first seizures and the survival percentage in young and adult animals. Determination of AChE activity in the hippocampus and striatum of young and adult animals, after pilocarpine-induced status epilepticus, demonstrated that pretreatment with MPH reduced AChE activity only in the striatum. Conclusion: Our findings suggest that MPH has proconvulsant action and cholinergic neurotransmission system can play a role in this effect

Booklet and Motivational Interviewing to Promote Self-efficacy in Parents/Caregivers of Children with Asthma:A Clinical Trial

Background: Asthma is the most common chronic disease in childhood which accounts for numerous annual hospitalizations due to a lack of management and proper management of the disease. Thus, this study aimed to evaluate the effect of using an educational booklet with or without combination with motivational interviewing (MI) on the self-efficacy of parents/caregivers in the control and management of childhood asthma. Methods: A clinical trial was carried out with 86 parents/caregivers of children with asthma aged between 2 and 12 years who were followed up in primary health care units from March 2019 to December 2020. Participants were randomly assigned to two groups: one of the groups read the booklet and the other read the booklet combined with the MI. The Brazilian version of the Self-Efficacy and Their Child’s Level of Asthma Control scale was applied before and 30 days after the intervention for assessment of self-efficacy. Data were analyzed using SPSS version 20.0 and R 3.6.3 software. P values&lt;0.05 were considered significant. Results: There were 46 participants in the booklet group and 40 in the booklet and MI group. Both groups were effective in increasing total self-efficacy scores after the intervention (P&lt;0.001). No statistically significant difference was found between the scores of the two groups (P=0.257). Conclusion: The educational booklet with or without combination with MI can increase the self-efficacy of parents/caregivers of children with asthma. The findings could be considered by healthcare providers for the empowerment of caregivers of children with asthma in the control and management of their children’s asthma.</p

The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34(+) samples. However, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. Despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. Here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. We observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34(+) samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. The EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. Therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients