Cocaine-induced structural plasticity in frontal cortex correlates with conditioned place preference.

Contextual cues associated with previous drug exposure can trigger drug craving and seeking, and form a substantial obstacle in substance use recovery. Using in vivo imaging in mice, we found that cocaine administration induced a rapid increase in the formation and accumulation of new dendritic spines, and that measures of new persistent spine gain correlated with cocaine conditioned place preference. Our data suggest that new persistent spine formation in the frontal cortex may be involved in stimulant-related learning driving appetitive behavior

Breastfeeding among teenage and adult mothers in Brazil

OBJECTIVE: To estimate the prevalence of breastfeeding among teenage (younger than 20 years old) and adult mothers of six-month-old children and to identify factors associated with weaning. METHODS: A cross-sectional study of a sample of 237 teenage mothers and 239 adult mothers living in the city of Montes Claros, Brazil, whose babies were six-month-old at the time of the interview was carried out. Mothers answered a questionnaire at home. To assess factors associated with weaning, univariate, Mantel-Haenszel, and multiple logistic regression analyses were performed. RESULTS: Breastfeeding prevalence in children aged 6 months was 71.3% among teenage mothers and 77.4% among adult mothers (crude OR=1.38; p=0.128), but after adjusting for control variables the role of adolescence added considerable weight to weaning. Factors associated with weaning were: marital status, mother's occupation after delivery (both showed interaction with teenage years), difficulty to breastfeeding in the first days after delivery, and exclusive breastfeeding at the time of hospital discharge. CONCLUSIONS: The observed interactions with teenage in regard to weaning suggest that motherhood in this age group has unique features that should be further investigated.OBJETIVO: Estimar a prevalência de amamentação entre mães adolescentes (menores de 20 anos de idade) e não-adolescentes aos seis meses de vida da criança e identificar fatores associados ao desmame. MÉTODOS: Estudo transversal feito por amostragem, com entrevista aplicada no domicílio a 237 mães adolescentes e 239 não-adolescentes, residentes na cidade de Montes Claros, MG, com filhos de seis meses de idade no momento da entrevista. Para avaliar fatores associados ao desmame, realizou-se análise univariada, seguida de bivariada de Mantel-Haenszel e regressão logística múltipla. RESULTADOS: A prevalência de amamentação aos seis meses de vida foi de 71,3% entre as mães adolescentes e 77,4% entre as não-adolescentes (OR bruta =1,38; p=0,128). O papel da adolescência no desmame ganhou importância com o ajuste para variáveis de controle. Os fatores associados ao desmame foram: estado conjugal, atividade fora do lar após o parto (esses dois apresentaram interação com adolescência), dificuldade para amamentar nos primeiros dias e aleitamento exclusivo ao peito na alta hospitalar. CONCLUSÕES: As interações observadas com a adolescência em relação ao desmame sugerem que a maternidade nessa faixa etária tem peculiaridades que a mantém como objeto especial de estudo.Universidade Estadual de Montes ClarosUniversidade Federal de São Paulo (UNIFESP) Departamento de Medicina PreventivaUNIFESP, Depto. de Medicina PreventivaSciEL

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.With its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM. Here, a structural modification of IVM to produce novel molecular hybrids by using sub-structures of 4- and 8-aminoquinolines, the time-tested antiplasmodial agents used for treating the blood and hepatic stage of Plasmodium infections, respectively, is presented. Successful isolation of regioisomers and epimers has been demonstrated, and the evaluation of their in vitro antiplasmodial activity against both the blood stages of P. falciparum and the hepatic stages of P. berghei have been undertaken. These compounds displayed structure-dependent antiplasmodial activity, in the nM range, which was more potent than that of IVM, its aglycon or primaquine, highlighting the superiority of this hybridization strategy in designing new antiplasmodial agents.KS thanks SERB, DST for the grant (EMR/2017/000520) and Guru Nanak Dev University, Amritsar for funding under the RUSA-II scheme as well as facilities. MP acknowledges Fundação para a Ciência e Tecnologia, Portugal, for Grant PTDC-SAU-INF-29550/2017. LS is thankful to University Grants Commission (UGC), New Delhi for funding under Rajiv Gandhi National Fellowship.info:eu-repo/semantics/publishedVersio

EDUCADORAS LEIGAS DE CRECHES COMUNITÁRIAS - DA AÇÃO À QUALIFICAÇÃO DOCENTE

O presente artigo “Educadoras Leigas de Creches Comunitárias - Da Ação à Qualificação Docente” é parte da pesquisa intitulada Processo de Formação Docente das Educadoras Leigas de Creches Comunitárias e tem como objetivo analisar como ocorre a construção identitária de professora pelas educadoras leigas atuantes em creches comunitárias conveniadas com a Prefeitura Municipal de Porto Alegre/RS, matriculadas no curso de ensino médio Normal. Este estudo se valeu, predominantemente, da abordagem qualitativa, pautou-se em estudo de caso, tendo sido utilizados instrumentos metodológicos, como questionário, entrevistas semi-estruturadas, observação de campo e análise documental para compor o corpus da pesquisa. Buscou-se identificar, a partir da fala das alunas, protagonistas desse processo, bem como de seus interlocutores, professores do curso e coordenadoras pedagógicas das creches comunitárias onde trabalham, como acontece a passagem de educadora leiga à professora e se essas imprimem ressignificações na prática pedagógica cotidiana com crianças na creche. Palavras-chave: Formação de educadoras leigas Educação Infantil - Curso Normal - habilitação Educação Infantil - Formação de professores

O reconto escrito: um estudo realizado com alunos do 3º ano

Mestrado em Educação Pré-Escolar e Ensino no 1º Ciclo do Ensino BásicoO presente relatório de estágio teve como principal objetivo compreender de que forma é possível desenvolver competências de compreensão leitora e de produção escrita em alunos do 1.º Ciclo do Ensino Básico através do estudo da estrutura da narrativa e do reconto escrito. Neste sentido, foi realizado um estudo de investigação-ação junto de alunos do 3.º ano de escolaridade, da Escola Básica de Chave, situada na Gafanha da Nazaré. O texto narrativo encontra-se presente na rotina diária do ser humano e acompanha-o desde sempre, sendo um dos primeiros tipos de texto com o qual contacta. A apreensão da sua estrutura é feita de uma forma quase intuitiva. Contudo, não quer dizer que esta mesma aquisição natural das propriedades do texto narrativo faça com que o indivíduo seja um leitor ou produtor de textos eficiente. Nesta medida, é fundamental que a escola e o professor forneçam ao aluno ferramentas que o ajudem a desconstruir o texto, no sentido de melhor perceber a sua constituição e características a ele inerentes. De modo a trabalhar este tipo de texto, especificamente o género “reconto”,junto do grupo de alunos, foi utilizado um modelo de estrutura do texto narrativo construído através dos modelos apontados por três autores que dedicaram o seu estudo à temática em evidência. De acordo com a análise de dados feita às atividades realizadas é de salientar que os alunos demonstram uma maior facilidade em certas categorias do texto narrativo – situação inicial (identificação dos personagens e ação inicial) e situação final (resultado final das ações) – em detrimento de outras – desenvolvimento (identificação das peripécias e sua localização espácio-temporal). Grosso modo, é necessário efetuar junto dos alunos do 1.º Ciclo do Ensino Básico atividades didáticas devidamente planeadas e fundamentadas que permitam trabalhar as diversas potencialidades do texto narrativo. Este projeto foi realizado de forma gradual e sistematizada de modo a ajudar o aluno a consciencializar-se da estruturação de texto do género narrativo com o intuito de desenvolver uma boa capacidade de compreensão leitora e de produção escrita.This dissertation aims to examine ways of development of understanding skills regarding reading and writing production by Primary School students towards the study of narrative structure and written recount. Consequently, it was carried an investigation-action study with 3rd grade students from Chave’s Primary School, located in Gafanha da Nazaré. The narrative text represents a textual genre present on human’s daily routine and one of the first text types that humans explore ever since. The apprehension of its structure is made almost intuitively. Even so, it does not implicate that individuals are readers or efficient text producers. Regarding this, it is essential that the school and the teacher provide tools to the student for the deconstruction of the text regardingtheunderstanding of its constitution and its characteristics. In order to explore this textual genre along with the students it was used a model of structure designated by three authors that dedicated their study to this theme. According to the data analysis of these activities it is important to emphasize that some students have had less issuesabout certain categories of narrative text – initial situation (character identification and initial action) and final situation (actions final result) – in detriment of others – development ( identification of actions and its location in space and time). Finally, it is essential to develop along with Primary School students didactic activities properly planned and justified that allow to work the various potentialities of narrative text. This work ought to be done gradually and in a systematized way to help the student to be sensitive to the structure of narrative text genre and aiming the development of good reading comprehension and writing production skills

Metronomic anti-cancer therapy: A multimodal therapy governed by the tumor microenvironment

Producción CientíficaThe concept of cancer as a systemic disease, and the therapeutic implications of this, has gained special relevance. This concept encompasses the interactions between tumor and stromal cells and their microenvironment in the complex setting of primary tumors and metastases. These factors determine cellular co-evolution in time and space, contribute to tumor progression, and could counteract therapeutic effects. Additionally, cancer therapies can induce cellular and molecular responses in the tumor and host that allow them to escape therapy and promote tumor progression. In this study, we describe the vascular network, tumor-infiltrated immune cells, and cancer-associated fibroblasts as sources of heterogeneity and plasticity in the tumor microenvironment, and their influence on cancer progression. We also discuss tumor and host responses to the chemotherapy regimen, at the maximum tolerated dose, mainly targeting cancer cells, and a multimodal metronomic chemotherapy approach targeting both cancer cells and their microenvironment. In a combination therapy context, metronomic chemotherapy exhibits antimetastatic efficacy with low toxicity but is not exempt from resistance mechanisms. As such, a better understanding of the interactions between the components of the tumor microenvironment could improve the selection of drug combinations and schedules, as well as the use of nano-therapeutic agents against certain malignancies.Ministerio de Ciencia e Innovación y Ministerio de Universidades - CIBER-BBN e ISCIII (DTS19/00162 y PID2019-106386RB-I00

Methylphenidate and pharmacological cognitive enhancement: social representations of university students

The article aims to present the outcome of the investigation of social representations of 20 university students on the use of methylphenidate to improve cognitive performance in healthy people. In this qualitative and exploratory research, 20 university students between 18 and 25 years from health and humanities courses were divided into 3 focus groups to discuss about Pharmacological Cognitive Enhancement. Data analysis revealed that these students had greater tolerance to methods that alter neurobiology in favor of the social ideal of improving the performance of people. However, respondents expressed great concern about this procedure intensifying injustices and inequalities between people, especially in societies where there are already significant social differences. Thus, although the subject is little studied in Brazil, the analysis of data from this research suggests that Pharmacological Cognitive Enhancement is an important and relevant topic. Not only because this practice is related to construction and maintenance of individuals' subjectivity in a society that prioritizes the improvement in cognitive performance, but also because of the risk that this practice interferes in matters of social justice and equality.O artigo tem por objetivo apresentar o resultado da investigação das representações sociais de 20 estudantes universitários sobre o uso de metilfenidato para aprimorar o desempenho cognitivo em pessoas saudáveis. Nesta pesquisa qualitativa, de cunho exploratório, 20 universitários entre 18 e 25 anos, oriundos de cursos das áreas de saúde e humanas, foram distribuídos em três grupos focais para debater sobre o Aprimoramento Cognitivo Farmacológico. A análise dos dados revelou que entre esses estudantes houve uma maior tolerância aos métodos que alteram a neurobiologia a favor do ideal social de melhoria da performance das pessoas. Contudo, os entrevistados expressaram grande preocupação com a possibilidade de este procedimento vir a intensificar injustiças e desigualdades entre as pessoas, principalmente nas sociedades em que já existem significativas diferenças sociais. Assim, apesar de o tema ser pouco estudado no Brasil, a análise dos dados da presente investigação sugere que o Aprimoramento Cognitivo Farmacológico é um assunto atual e relevante. Não apenas por esta prática estar relacionada à construção e manutenção da subjetividade dos indivíduos em uma sociedade que prioriza a melhoria da performance cognitiva, mas também pelo risco de esta interferir em questões de igualdade e justiça social

A Randomized Trial Comparing Immediate versus Delayed Treatment of Anemia with Once-Weekly Epoetin Alfa in Patients with Non-small Cell Lung Cancer Scheduled to Receive First-Line Chemotherapy

Introduction:This study evaluated the safety/efficacy of once-weekly (QW) epoetin alfa measured by quality of life (QOL), hemoglobin (Hb), transfusion incidence, tumor response, and survival in patients with chemotherapy-naïve, advanced non-small cell lung cancer (NSCLC).Methods:Stage IIIB/IV NSCLC patients with Hb ≥11 to <15 g/dl scheduled for at least 8 weeks of first-line chemotherapy were randomized to subcutaneously receive 40,000 U of epoetin alfa QW at chemotherapy initiation (immediate) or no epoetin alfa unless Hb decreased to ≤10 g/dl (delayed). The primary efficacy variable was change in QOL for immediate versus delayed intervention. Target accrual was 320 patients.Results:The study was terminated early because of slow accrual; of 216 patients enrolled, 211 were evaluable for efficacy. Hb was maintained in the immediate group, but it decreased in the delayed group (12.9 versus 11.6 g/dl final values, respectively). Numerically, fewer immediate patients required transfusions versus delayed patients. Mean QOL scores, modestly declining in both groups from baseline to final measurement, were not significantly different between groups. Tumor response and median overall survival were similar between groups. Epoetin alfa was well tolerated, with a similar thrombovascular event rate between groups.Conclusion:Epoetin alfa in subcutaneous doses of 40,000 U QW, given immediately at chemotherapy initiation for advanced NSCLC, was well tolerated, and it effectively maintained Hb, leading to a reduced transfusion incidence versus delayed epoetin alfa. Overall QOL scores were higher than typical in this population, decreasing slightly during treatment in both groups. Overall survival was similar between groups, with no evidence of a negative effect by early epoetin alfa intervention

The importance of monitoring cerebral oxygenation in non brain injured patients

Over the past few years, the use of non-invasive neuromonitoring in non-brain injured patients has increased, as a result of the recognition that many of these patients are at risk of brain injury in a wide number of clinical scenarios and therefore may benefit from its application which allows interventions to prevent injury and improve outcome. Among these, are post cardiac arrest syndrome, sepsis, liver failure, acute respiratory failure, and the perioperative settings where in the absence of a primary brain injury, certain groups of patients have high risk of neurological complications. While there are many neuromonitoring modalities utilized in brain injured patients, the majority of those are either invasive such as intracranial pressure monitoring, require special skill such as transcranial Doppler ultrasonography, or intermittent such as pupillometry and therefore unable to provide continuous monitoring. Cerebral oximetry using Near infrared Spectroscopy, is a simple non invasive continuous measure of cerebral oxygenation that has been shown to be useful in preventing cerebral hypoxemia both within the intensive care unit and the perioperative settings. At present, current recommendations for standard monitoring during anesthesia or in the general intensive care concentrate mainly on hemodynamic and respiratory monitoring without specific indications regarding the brain, and in particular, brain oximetry. The aim of this manuscript is to provide an up-to-date overview of the pathophysiology and applications of cerebral oxygenation in non brain injured patients as part of non-invasive multimodal neuromonitoring in the early identification and treatment of neurological complications in this population