Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis.

Background: Previous studies found high but very variable levels of tetranor-PGEM and PGDM (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF). This study aims to assess the role of cyclooxygenase COX-1 and COX-2 genetic polymorphisms in PG production and of PG metabolites as potential markers of symptoms' severity and imaging findings. Methods: A total of 30 healthy subjects and 103 pwCF were included in this study. Clinical and radiological CF severity was evaluated using clinical scoring methods and chest computed tomography (CT), respectively. Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. Variants in the COX-1 gene (PTGS1 639 C>A, PTGS1 762+14delA and COX-2 gene: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were also analyzed. Results: PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Conclusions: These results suggest that urinary PG level testing can be used as a biomarker of CF severity. COX genetic polymorphisms are not involved in the variability of PG production.

Glycine transporter-1 inhibition by NFPS promotes neuroprotection against striatal damage models.

The striatum, an essential component of the brain's motor and reward systems, plays a pivotal role in a wide array of cognitive processes. Its dysfunction is a hallmark of neurodegenerative diseases like Parkinson's disease (PD) and Huntington's disease (HD), leading to profound motor and cognitive deficits. These conditions are often related to excitotoxicity, primarily due to overactivation of NMDA receptors (NMDAR). In the synaptic cleft, glycine transporter type 1 (GlyT1) controls the glycine levels, a NMDAR co-agonist, which modulates NMDAR function. This research explored the neuroprotective potential of NFPS, a GlyT1 inhibitor, in murine models of striatal injury. Employing models of neurotoxicity induced by 6-hydroxydopamine (PD model) and quinolinic acid (HD model), we assessed the effectiveness of NFPS pre-treatment in maintaining the integrity of striatal neurons and averting neuronal degeneration. The results indicated that NFPS pre-treatment conferred significant neuroprotection, reducing neuronal degeneration, protecting dopaminergic neurons, and preserving dendritic spines within the striatum. Additionally, this pre-treatment notably mitigated motor impairments resulting from striatal damage. The study revealed that GlyT1 inhibition led to substantial changes in the ratios of NMDAR subunits GluN2A/GluN1 and GluN2B/GluN1, 24 h after NFPS treatment. These findings underscore the neuroprotective efficacy of GlyT1 inhibition, proposing it as a viable therapeutic strategy for striatum-related damage.

Assessment of Cellulose Nanofiber-Based Elastase Biosensors to Inflammatory Disease as a Function of Spacer Length and Fluorescence Response.

Inflammatory disease biomarker detection has become a high priority in point-of-care diagnostic research in relation to chronic wounds, with a variety of sensor-based designs becoming available. Herein, two primary aspects of biosensor design are examined: (1) assessment of a cellulose nanofiber (CNF) matrix derived from cotton ginning byproducts as a sensor transducer surface; and (2) assessment of the relation of spacer length and morphology between the CNF cellulose backbone and peptide fluorophore as a function of sensor activity for porcine pancreatic and human neutrophil elastases. X-ray crystallography, specific surface area, and pore size analyses confirmed the suitability of CNF as a matrix for wound care diagnostics. Based upon the normalized degree of substitution, a pegylated-linker connecting CNF transducer substrate to peptide fluorophore showed the greatest fluorescence response, compared to short- and long-chain alkylated linkers.

Psychometric properties of the Portuguese version of the physical activity parenting practices questionnaire.

BACKGROUND: Adopting a healthy lifestyle, including regular physical activity, is often part of interventions targeting childhood overweight and obesity. However, to properly inform the objectives of the intervention, reliable psychometric measures are needed to better understand children's and their families necessities and characteristics. OBJECTIVES: To evaluate the psychometric properties of the Physical Activity Parenting Practices questionnaire in a community sample of Portuguese parents of children aged 5-10, assess measurement invariance across children's weight status, and construct validity. METHODS: Five hundred three parents completed the Portuguese version of the Physical Activity Parenting Practices (PAPP) questionnaire, a sociodemographic questionnaire, the Comprehensive Feeding Practices Questionnaire, and the Lifestyle Behavior Checklist. A subsample (n = 125) completed the PAPP questionnaire 1 month later. Data analyses were performed using R's lavaan (version 0.6-12) and psych (version 2.2.9) packages. RESULTS: Confirmatory factor analyses revealed good psychometric properties for the PAPP's single-factor Encouragement scale and the three-factor Discouragement scale. Configural, metric, and scalar invariance were found across parents of children with different weight statuses for both scales' factor structures. Internal reliability ranged from α = .64 to α = .89, and test-retest reliability ranged from r = .57 to r = .74. CONCLUSIONS: The constructs evaluated by PAPP questionnaire revealed adequate validity. The Portuguese version of the PAPP questionnaire is a reliable measure to assess relevant physical activity parenting practices, capable of differentiating the practices of parents with children of different weight statuses, and useful for both research and intervention purposes.

Effect of continuous sugarcane bagasse-derived biochar application on rainfed cotton (Gossypium hirsutum L.) growth, yield and lint quality in the humid Mississippi delta.

Optimizing soil health through soil amendments is a promising strategy for enhancing rainwater efficiency for stabilizing crop production. Biochar, obtained by torrefaction of sugarcane bagasse, a byproduct from sugar mills, has a high potential for its use as a soil amendment, which can boost crop yields, but needs further field trials for its adoption in farming systems. A field study was conducted during 2019-2021 at Stoneville, Mississippi, to assess rainfed cotton (Gossypium hirsutum L.) production under four biochar levels (0, 10, 20, and 40 t ha-1) on Dundee silt loam soil. The effects of biochar on cotton growth and lint yield and quality were examined. Biochar levels had no significant impact on cotton lint and seed yield for the first two years. Still, in the third year, a significant increase in lint yield by 13 and 21.7% was recorded at 20 and 40 t ha-1 biochar levels, respectively. In the third year, lint yields were 1523, 1586, 1721, and 1854 kg ha-1 at 0, 10, 20 and 40 t ha-1 biochar levels, respectively. Similarly, cotton seed yield increased by 10.8% and 13.4% in 20 and 40 t ha-1 biochar plots. This study demonstrated that successive biochar applications at 20 or 40 t ha-1 can enhance cotton lint and seed yields under rainfed conditions. These improved yields with biochar did not produce increased net returns due to the increased production costs. Many lint quality parameters were unaffected except for micronaire, fiber strength and fiber length. However, potential long-term benefits of enhanced cotton production from biochar application beyond the length of the study merit further investigation. Additionally, biochar application is more relevant when accrued carbon credits through carbon sequestration outweigh the increased production costs due to biochar application.

First Report of Peach Scab Caused by Cladosporium tenuissimum in Mexico.

Peach (Prunus persica) is one of the most popular stone fruits in the world. From 2019 to 2022, typical scab symptoms were observed on 70% of peach fruits in a commercial orchard in Tepeyahualco, Puebla, Mexico (19°30'38"N 97°30'57"W). Fruit symptoms are black circular lesions of 0.3 mm in diameter. The fungus was isolated from symptomatic fruit pieces that were surface sterilized with 1% sodium hypochlorite for 30 s, rinsed in autoclaved distilled water three times, placed on PDA medium, and incubated at 28°C in darkness for 9 days. Cladosporium-like colonies were isolated. Pure cultures were obtained by single spore culture. Colonies on PDA showed aerial mycelium abundant, smoke-grey, fluffy, and with margin glabrous to feathery. Conidiophores were solitary, long, intercalary conidia narrow erect, macro- and micronematous, straight or slightly flexuous, cylindrical-oblong, olivaceous-brown, and often subnodulose. Conidia (n= 50) catenate in branched chains, obovoid to limoniform, sometimes globose, aseptate, olivaceous-brown, apically rounded, 3.1 to 5.1 × 2.5 to 3.4 µm. Secondary ramoconidia (n= 50) were fusiform to cylindrical, smooth-walled, 0-1-septate, pale brown or pale olivaceous-brown, measuring 9.1 to 20.8 × 2.9 to 4.8 µm. Morphology was consistent to that described for Cladosporium tenuissimum (Bensch et al. 2012; 2018). A representative isolate was deposited in the Culture Collection of Phytopathogenic Fungi of the Department of Agricultural Parasitology at the Chapingo Autonomous University under the accession number UACH-Tepe2. To further confirm the morphological identification, total DNA was extracted using the cetyltrimethylammonium bromide method (Doyle and Doyle 1990). The internal transcribed spacer (ITS) region, partial sequences of the translation elongation factor 1-alpha (EF1-α) and actin (act) genes were amplified by PCR, and sequenced using the primer pairs ITS5/ITS4 (White et al. 1990), EF1-728F/986R, and ACT-512F/783R (Carbone and Kohn 1999), respectively. The sequences were deposited in GenBank under the accession numbers OL851529 (ITS), OM363733 (EF1-α), and OM363734 (act). BLASTn searches in GenBank showed 100% identity with available sequences of Cladosporium tenuissimum accession (ITS: MH810309; EF1-α: OL504967; act: MK314650). A phylogenetic analysis using the maximum likelihood method placed isolate UACH-Tepe2 in the same clade as C. tenuissimum. To verify the pathogenicity of the fungus, 20 healthy peach fruits were inoculated with four drops of 15 µl of a conidial suspension (1 × 106 spores /ml). Ten control fruit were treated with sterilized water. All the fruits were kept in a moist chamber at 25°C for 10 days. Circular and necrotic lesions were produced eight days after inoculation, whereas control fruits remained healthy. Pathogenicity test was conducted three times with similar results. Fungal colonies were reisolated from the artificially inoculated fruit, thus fulfilling Koch's postulates. Cladosporium tenuissimum has been previously reported to cause diseases on strawberry, cashew, papaya, and passionfruit in Brazil (Rosado et al. 2019; Santos et al. 2020), as well as diseases on pitaya, hydrangea, and carnation in China (Xu et al. 2020; Li et al. 2021; Xie et al. 2021). Cladosporium carpophilum is reported as the causal agent of peach scab. The environmental conditions for the development of C. carpophilum are 20-30 °C in warm humid areas (Lawrence and Zehr 1982), however, in this case the infection by C. tenuissinum occurred in a temperate semi-dry climate, with temperatures of 5 -15 °C and R.H. less than 50 % with an incidence of 80 %. To our knowledge, this is the first report of Cladosporium tenuissimum causing peach scab in Mexico and worldwide.

School Psychologists Practice and Profile Indicators Scale / Escala de Indicadores de Perfil e Atuação de Psicólogos Escolares

The purpose of this article is to describe the development process of a research instrument, in the format of a self-report scale, to investigate the school psychologists' profile, their competencies and professional activities indicators. It is based on the historical-cultural psychology, critical school psychology, and competence approach. Method The method used a review of evidence of theoretical and semantic validity of a scale for profile and competencies contains three guiding lines: (a) instructions and sociodemographic characterization of the participant, (b) profile and competencies of the school psychologist (40 items), and (c) school psychology practices (30 items). Several procedures were carried out for the development and validation of the instrument. The initial version was reviewed by two groups of expert judges, from Brazil and Portugal. The judges' review led to the removal of some items. The new version was submitted to pilot studies for theoretical and semantic validation. Results As a result of these validations, the most recent version of the scale was obtained for use in Brazil and Portugal. Conclusion It is expected that the instrument will contribute to the theoretical-conceptual and methodological expansion of the psychologist's profile, affecting how interventions will be carried out in educational and academic spaces from an institutional and collective perspective.

O objetivo deste artigo é descrever o processo de elaboração de um instrumento de pesquisa, no formato de uma escala de autorrelato, para levantamento de indicadores de perfil, competências e principais atividades profissionais do psicólogo escolar. O estudo está fundamentado na psicologia histórico-cultural, na psicologia escolar crítica e na abordagem de competências. Método O método utilizou uma revisão das evidências de validade teórica e semântica de uma escala para perfil e competências contendo três eixos orientadores: (a) instruções e caracterização sociodemográfica do participante, (b) perfil e competências do psicólogo escolar (40 itens) e (c) atuação em psicologia escolar (30 itens). Diversos procedimentos foram realizados para o desenvolvimento e validação do instrumento. A versão inicial foi revisada por dois grupos de juízes especialistas, do Brasil e de Portugal. A revisão dos juízes levou à retirada de alguns itens. A nova versão foi submetida a estudos pilotos para validação teórica e semântica. Resultados Como resultado dessas validações, obteve-se a versão mais recente da escala para uso no Brasil e em Portugal. Conclusão Espera-se que o instrumento contribua para a ampliação teórico-conceitual e metodológica acerca do perfil do psicólogo, impactando no olhar sobre intervenções realizadas nos espaços educativos e acadêmicos em uma perspectiva institucional e coletiva.

Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.

BACKGROUND: The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ). METHODS: We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number. RESULTS: PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects. CONCLUSION: Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.

Group Triple P Intervention Effects on Children and Parents: A Systematic Review and Meta-Analysis.

Supporting parents through the delivery of evidence-based parenting interventions (EBPI) is a way of promoting children's rights, given the known benefits to child development and family wellbeing. Group Triple P (GTP) is an EBPI suitable for parents of children aged 2-12 years, who experience parenting difficulties, and/or child behavior problems. Even though GTP has been intensively studied, information lacks on the magnitude of its effects, considering the risk of bias within and across prior research. To address this, a systematic review and meta-analysis (PROSPERO registration CRD42019085360) to evaluate the effects of GTP on child and parent outcomes at short- and longer-term was performed. Through a systematic search of a set of databases, 737 research papers were identified, and 11 trials were selected. The risk of bias within and across studies was evaluated. Significant positive effects of GTP were found immediately after the intervention for child behavior problems, dysfunctional parenting practices, parenting sense of competence, psychological adjustment, parental stress levels, conflict, and relationship quality. Six months after the intervention, positive effects were found only for child behavior problems. Data suggest that GTP might be an effective EBPI leading to positive family outcomes. Substantial risk of bias was found, highlighting the importance of improving the quality of research.

ROS-scavenging-associated transcriptional and biochemical shifts during nectarine fruit development and ripening.

ROS are known as toxic by-products but also as important signaling molecules playing a key role in fruit development and ripening. To counteract the negative effects of ROS, plants and fruit own multiple ROS-scavenging mechanisms aiming to ensure a balanced ROS homeostasis. In the present study, changes in specific ROS (i.e. H2O2) as well as enzymatic (SOD, CAT, POX, APX) and non-enzymatic (phenylpropanoids, carotenoids and ascorbate) ROS-scavenging systems were investigated along four different stages of nectarine (cv. 'Diamond Ray') fruit development and ripening (39, 70, 94 and 121 DAFB) both at the metabolic (28 individual metabolites or enzymes) and transcriptional level (24 genes). Overall, our results demonstrate a complex ROS-related transcriptome and metabolome reprogramming during fruit development and ripening. At earlier fruit developmental stages an increase on the respiration rate is likely triggering an oxidative burst and resulting in the activation of specific ethylene response factors (ERF1). In turn, ROS-responsive genes or the biosynthesis of specific antioxidant compounds (i.e. phenylpropanoids) were highly expressed or accumulated at earlier fruit developmental stages (39-70 DAFB). Nonetheless, as the fruit develops, the decrease in the fruit respiration rate and the reduction of ERF1 genes leads to lower levels of most non-enzymatic antioxidants and higher accumulation of H2O2. Based on available literature and the observed accumulation dynamics of H2O2, it is anticipated that this compound may not only be a by-product of ROS-scavenging but also a signaling molecule accumulated during the ripening of nectarine fruit.

Análise política da atuação do Conselho Nacional de Saúde na construção da política de saúde no Brasil no período de 2014-2017 / Análisis político de actuación del Consejo Nacional de Salud en la construcción de la política de salud en Brasil en el período de 2014/2017 / Political analysis of the National Health Council's performance in the construction of health policy in Brazil in the period 2014-2017

Objetivou-se analisar a atuação do Conselho Nacional de Saúde no núcleo do processo decisório da política de saúde entre 2014-2017. A análise foi baseada nos projetos políticos em disputa na arena política da saúde e nos projetos dos governos de Dilma e de Temer. Com a mudança no projeto de governo, o Conselho passou a atuar pela via judicial, além de pelas vias social e parlamentar, passando do alinhamento (crítico) à franca oposição, até sua neutralização com o boicote da participação do Conselho nas discussões de pautas da política de saúde nos anos 2016-2017. Embora não tenha tido poder suficiente para mudar a correlação de forças em torno do desmonte do Sistema Único de Saúde (SUS), o Conselho figurou-se em um bloco político de resistência e de enfrentamento em defesa do SUS constitucional. (AU)

El objetivo fue el análisis de la actuación del Consejo Nacional de Salud en el núcleo del proceso de decisión de la política de salud entre 2014-2017. El análisis tuvo como base los proyectos políticos en disputa en la arena política de la salud y en los proyectos de los gobiernos Dilma y Temer. Con el cambio en el proyecto de gobierno, el Consejo pasó a actuar, además de en las vías social y parlamentaria, en la vía judicial, pasando del alineamiento (crítico) a la franca oposición, hasta su neutralización, con el boicot de la participación del Consejo en las discusiones de pautas de la política de salud en los años 2016-2017. Aunque no haya tenido poder suficiente para cambiar la correlación de fuerzas alrededor del desmontaje del Sistema Brasileño de Salud (SUS), el Consejo se configuró como un bloque político de resistencia y de enfrentamiento, en defensa del SUS constitucional. (AU)

This study aimed to analyze the role of the National Health Council in the core of the decision-making process of health policy in the period 2014-2017. The analysis was based on the political disputed projects in the health policy sphere and on the government projects of former Presidents Dilma Rousseff and Michel Temer. Due to the government's project change, in addition to the social and parliamentary channels, the Council started to act through the judicial channel as well, moving from critical alignment to outright opposition until its neutralization, with the Council's participation boycott in the health policy agenda discussions in the period 2016-2017. Although it did not have enough power to change the balance of forces surrounding the deconstruction of the Brazilian National Health System (SUS), the Council was part of a political bloc of resistance and confrontation in defense of the constitutional SUS. (AU)

Health councils and conferences in Brazil: an integrative review. / Conselhos e conferências de saúde no Brasil: uma revisão integrativa.

This paper aimed to identify the thinking currents used for scientific production on health councils and conferences, from 1990 to 2017. This is an integrative review of literature carried out at the SciELO, LILACS and CAPES journals portals that resulted in the selection of 152 papers. They were analyzed by year of publication, author's institutional origin, dissemination media, object and type of study and theoretical approach. We identified that a gradual increase occurred in the number of publications over the study period and most empirical studies (92.8%) do not explicitly state the use of any theoretical approach in data analysis. The structuralist, post-structuralist and neo-institutionalist approaches used were mediated by a theoretical model, medium-range theories and concepts of authors of the European, North American and Latin American traditions. The knowledge produced about health council and conference in Brazil may benefit even more from the density of theoretical approaches to social and political sciences.

O objetivo desse artigo consiste em identificar as correntes de pensamento utilizadas para a produção científica sobre conselhos e conferências de saúde, no período de 1990 a 2017. Trata-se de uma revisão integrativa de literatura realizada nas bases SciELO, LILACS e portal de periódicos da CAPES que resultou na seleção de 152 trabalhos. Estes foram analisados segundo ano de publicação, procedência institucional dos autores, veículo de divulgação, objeto e tipo de estudo e abordagem teórica. Identificou-se um aumento gradativo no número de publicações ao longo do período estudado, sendo que a maioria dos estudos com base empírica (92,8%) não explicita, nominalmente, a utilização de qualquer abordagem teórica na análise dos dados. As abordagens estruturalista, pós-estruturalista e neo-institucionalista utilizadas foram mediadas por modelo teórico, teorias de médio alcance e conceitos de autores da tradição européia, norte-americana e latino-americana. O conhecimento produzido sobre conselho e conferência de saúde no Brasil pode se beneficiar ainda mais da densidade das abordagens teóricas das ciências sociais e políticas.

Conselhos e conferências de saúde no Brasil: uma revisão integrativa / Health councils and conferences in Brazil: an integrative review

Resumo O objetivo desse artigo consiste em identificar as correntes de pensamento utilizadas para a produção científica sobre conselhos e conferências de saúde, no período de 1990 a 2017. Trata-se de uma revisão integrativa de literatura realizada nas bases SciELO, LILACS e portal de periódicos da CAPES que resultou na seleção de 152 trabalhos. Estes foram analisados segundo ano de publicação, procedência institucional dos autores, veículo de divulgação, objeto e tipo de estudo e abordagem teórica. Identificou-se um aumento gradativo no número de publicações ao longo do período estudado, sendo que a maioria dos estudos com base empírica (92,8%) não explicita, nominalmente, a utilização de qualquer abordagem teórica na análise dos dados. As abordagens estruturalista, pós-estruturalista e neo-institucionalista utilizadas foram mediadas por modelo teórico, teorias de médio alcance e conceitos de autores da tradição européia, norte-americana e latino-americana. O conhecimento produzido sobre conselho e conferência de saúde no Brasil pode se beneficiar ainda mais da densidade das abordagens teóricas das ciências sociais e políticas.

Abstract This paper aimed to identify the thinking currents used for scientific production on health councils and conferences, from 1990 to 2017. This is an integrative review of literature carried out at the SciELO, LILACS and CAPES journals portals that resulted in the selection of 152 papers. They were analyzed by year of publication, author's institutional origin, dissemination media, object and type of study and theoretical approach. We identified that a gradual increase occurred in the number of publications over the study period and most empirical studies (92.8%) do not explicitly state the use of any theoretical approach in data analysis. The structuralist, post-structuralist and neo-institutionalist approaches used were mediated by a theoretical model, medium-range theories and concepts of authors of the European, North American and Latin American traditions. The knowledge produced about health council and conference in Brazil may benefit even more from the density of theoretical approaches to social and political sciences.

A new lipophilic amino alcohol, chemically similar to compound FTY720, attenuates the pathogenesis of experimental autoimmune encephalomyelitis by PI3K/Akt pathway inhibition.

Experimental autoimmune encephalomyelitis (EAE) is one of the main animal models used for the study of Multiple Sclerosis (MS). Long-chain lipophilic amino alcohols with immunoregulatory activities have already been studied in some models of inflammatory diseases, but the action of these compounds in EAE and MS is still unknown. In this study, we investigated whether the lipophilic amino alcohol 4b would act to improve the clinical signs of EAE and reduce the demyelination process and the neuroinflammatory parameters in the spinal cord, as well as the inflammatory process in the inguinal lymph nodes, of C57Bl/6 mice induced with EAE after stimulation with MOG35-55 and pertussis toxin. The 4b treatment (1.0 mg/kg/day) was orally administered, starting on the day of onset of clinical signs of the disease (10th) and ending on the 20th day after immunization. This treatment was able to reduce the cell count on the inguinal lymph nodes, the migration of inflammatory cells into the central nervous system (CNS), as well as the processes of microgliosis, astrogliosis, and the production of chemokines and pro-inflammatory cytokines, thus increasing the IL-10 anti-inflammatory cytokine levels in EAE mice. The inhibition of Akt phosphorylation in the CNS of EAE mice after treatment with 4b indicates that the immunoregulatory action of 4b is related to the PI3K/Akt signaling pathway. Our results indicate the immunoregulatory efficacy of the new compound 4b in the control of some inflammatory parameters and in the glial proliferation. In addition, 4b was able to reduce the demyelination of neurons and the worsening of clinical signs of EAE as effectively as the compound FTY720, the first oral drug approved by the FDA for the treatment of MS.

Cannabidiol anticonvulsant effect is mediated by the PI3Kγ pathway.

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mechanistic target of rapamycin (mTOR) signaling pathway has been associated with several pathologies in the central nervous system (CNS), including epilepsy. There is evidence supporting the hypothesis that the PI3Kγ signaling pathway may mediate the powerful anticonvulsant properties associated with the cannabinoidergic system. This work aims to investigate if the anticonvulsant and neuroprotective effects of cannabidiol (CBD) are mediated by PI3Kγ. In vitro and in vivo experiments were performed on C57Bl/6 wild-type (WT) and PI3Kγ-/- mice. Behavioral seizures were induced by bilateral intra-hippocampal pilocarpine microinjection. Twenty-four hours after the first behavioral seizure, animals were perfused and their brains removed and processed, for histological analysis of neurodegeneration, microgliosis and astrocytosis. Primary cultures of hippocampal neurons were used for glutamate-induced cell death assay. CDB increased latency and reduced the severity of pilocarpine-induced behavioral seizures, as well as prevented postictal changes, such as neurodegeneration, microgliosis and astrocytosis, in WT animals, but not in PI3Kγ-/-. CBD in vivo effects were abolished by pharmacological inhibition of cannabinoid receptor or mTOR. In vitro, PI3Kγ inhibition or deficiency also changed CBD protection observed in glutamate-induced cell death assay. Thus, we suggest that the modulation of PI3K/mTOR signaling pathway is involved in the anticonvulsant and neuroprotective effects of CBD. These findings are important not only for the elucidation of the mechanisms of action of CBD, which are currently poorly understood, but also to allow the prediction of therapeutic and side effects, ensuring efficacy and safety in the treatment of patients with epilepsy.

New multifunctional AChE inhibitor drug prototypes protect against Aß-induced memory deficit.

Alzheimer's disease (AD) is the most incident neurodegenerative disorder, characterized by accumulation of extracellular amyloid-ß (Aß), intracellular neurofibrillary tangles, and cognitive impairment. The current available treatments are mainly based on the use of reversible acetylcholinesterase (AChE) inhibitors, which only ameliorate the cognitive deficits. However, it is important to develop disease-modifying drugs with neuroprotective effects in order to hamper the progression of the disease. Here, we describe the effect of four promising new drugs with additional protective characteristics on AD-associated memory changes. C57Bl/6 mice treated with the compounds received an intra-hippocampal injection of Aß1-40 and were submitted to the novel object recognition test, to evaluate memory recovery. All the compounds prevented memory loss. Compounds PQM-56 (4c) and PQM-67 (4g) showed the best profile of memory recovery, representing potential drug candidates for AD treatment.

Children in Situation of Intra-Family Violence: Concepts, Personal Experiences and Feelings of Undergraduate Medical Students / Crianças em Situação de Violência Intrafamiliar: Conceitos, Vivências e Sentimentos de Graduandos de Medicina

ABSTRACT: Introduction: The objective of the study was to learn about the concepts of violence among medical undergraduate students in the state of Bahia, their personal experiences with the phenomenon and advice regarding case referral. Method: a qualitative research was carried out with 20 undergraduate medical students from public institutions in the state of Bahia. The data were collected via the web through an electronic file made available by Google Forms. The students were informed about the page address through an e-mail. Results: Most of the students said that the topic of "Violence against Children" was addressed during their undergraduate years. Shared conceptions by most of the students on the subject are related to the definitions of violence as physical injuries inflicted on the victims, but broader definitions of social and subjective perception, encompassing different dimensions of the phenomenon were also identified. The most frequently cited feelings experienced in situations of violence were the following: helplessness, fear, sadness, unpreparedness, compassion, empathy, anger and rage. The difficulties that the students encountered in approaching the victims of violence stem from the lack of preparation in the training and from the positions related to the physicians themselves, such as fear of involvement and accountability. The inherent characteristics of children and distrust in protective services were also mentioned. Conclusion: Although the students reported having contact with the topic during graduation, most of them evaluated the training as insufficient. The lack of professional preparation to approach the medical-social issues, such as violence, has been partially attributed to the biologicist bias of the medical training. In this sense, we highlight the understanding of violence as an essentially social and historical phenomenon, to the detriment of the different dimensions of the illness that imply in the health-disease process. From this perspective, this bias obscure the recognition of the different manifestations of violence as objects of healthcare work, suggesting a need for a broader approach in medical education, which can help to contemplate the complexity of the subject.

Resumo: Introdução: O objetivo do estudo foi conhecer as concepções de violência entre acadêmicos dos cursos de Medicina do estado da Bahia, suas vivências com o fenômeno e orientação quanto ao encaminhamento dos casos. Métodos: Trata-se de uma pesquisa qualitativa realizada com 20 graduandos de cursos de Medicina de instituições públicas do estado da Bahia. Coletaram-se os dados por meio de um formulário eletrônico via web, disponibilizado no Google Forms, e os discentes foram informados sobre o endereço da página por meio de e-mail. Resultados: A maioria dos discentes afirmou que o tema violência contra a criança foi abordado durante a graduação. Concepções compartilhadas pela maioria dos discentes sobre o tema estão relacionadas às definições da violência como agravos físicos infringidos às vítimas, porém identificaram-se, além de aspectos subjetivos, definições mais amplas da percepção social, contemplando diferentes dimensões do fenômeno. Os sentimentos vivenciados em face de situações de violência mais frequentemente citados foram impotência, medo, tristeza, despreparo, compaixão, empatia, revolta e raiva. Para os discentes, as dificuldades encontradas na abordagem das vítimas da violência decorrem da falta de preparo na formação e de posicionamentos relacionados ao próprio médico, como medo de envolvimento e responsabilização. Mencionaram-se ainda características inerentes às crianças e descrença nos órgãos de proteção. Conclusão: Embora os discentes tenham relatado contato com o tema durante a graduação, a maioria avaliou a formação como insuficiente. O despreparo profissional para a abordagem de temas médico-sociais, a exemplo da violência, tem sido atribuído em parte ao viés biologicista da formação médica. Nesse sentido, destaca-se a compreensão da violência como fenômeno essencialmente sócio-histórico, em detrimento das diferentes dimensões do agravo que implicam o processo saúde-doença. Nessa perspectiva, tal viés obscurece o reconhecimento das diversas manifestações da violência como objeto do trabalho em saúde, sugerindo a necessidade de uma abordagem ampliada na formação médica que possa contemplar a complexidade do tema.

O acesso a medicamentos em sistemas universais de saúde - perspectivas e desafios / Access to medication in universal health systems - perspectives and challenges

RESUMO Este estudo objetivou analisar os desafios do acesso a medicamentos em quatro sistemas universais de saúde da Austrália, do Brasil, do Canadá e do Reino Unido. Estudo qualitativo crítico-reflexivo por meio de revisão integrativa da literatura. Um dos grandes desafios dos sistemas estudados é o da incorporação de medicamentos de alto custo, via análises de custo-efetividade para cumprir a difícil tarefa de conciliar a justiça social e a equidade no acesso com sustentabilidade econômica. Particularmente o Canadá, mesmo sendo um país desenvolvido, ainda vive o dilema de como financiar um sistema de saúde no qual o acesso a medicamentos também seja universal. O Brasil convive com duas realidades problemáticas: primeiro, dar acesso a medicamentos, já padronizados pelo Sistema Único de Saúde (SUS), diante de um financiamento diminuto, segundo, de maneira semelhante aos sistemas australiano, canadense e inglês, vive o dilema de como incorporar novos medicamentos eficazes e com viabilidade econômica, além da questão da judicialização da saúde, um fenômeno complexo resultante da fragilidade pública na organização, financiamento, consolidação do SUS.

ABSTRACT This study aimed to analyze the challenges of access to medicines in four universal health systems in Australia, Brazil, Canada and the United Kingdom. Critical-reflexive qualitative study through Integrative Literature Review. The great challenge of the systems studied is the incorporation of high-cost drugs, through cost-effectiveness analyses to fulfill the difficult task of reconciling social justice and access equity with economic sustainability. Canada, in particular, despite being a developed country, still deals with the dilemma of how to finance a health system in which access to medicines is also universal. Brazil deals with two problematic realities: first, to grant access to medicines that are already standardized by the Unified Health System (SUS), in the face of insufficient funding. Secondly, similarly to the Australian, Canadian, and English systems, the dilemma of how to incorporate new efficient medicines considering its economic feasibility, as well as the issue of health judicialization, a complex phenomenon resulting from public fragility in the organization, financing, and consolidation of the SUS.

A positive allosteric modulator of mGluR5 promotes neuroprotective effects in mouse models of Alzheimer's disease.

Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder. Despite advances in the understanding of its pathophysiology, none of the available therapies prevents disease progression. Excess glutamate plays an important role in excitotoxicity by activating ionotropic receptors. However, the mechanisms modulating neuronal cell survival/death via metabotropic glutamate receptors (mGluRs) are not completely understood. Recent data indicates that CDPPB, a positive allosteric modulator of mGluR5, has neuroprotective effects. Thus, this work aimed to investigate CDPPB treatment effects on amyloid-ß (Aß) induced pathological alterations in vitro and in vivo and in a transgenic mouse model of AD (T41 mice). Aß induced cell death in primary cultures of hippocampal neurons, which was prevented by CDPPB. Male C57BL/6 mice underwent stereotaxic surgery for unilateral intra-hippocampal Aß injection, which induced memory deficits, neurodegeneration, neuronal viability reduction and decrease of doublecortin-positive cells, a marker of immature neurons and neuronal proliferation. Treatment with CDPPB for 8 days reversed neurodegeneration and doublecortin-positive cells loss and recovered memory function. Fourteen months old T41 mice presented cognitive deficits, neuronal viability reduction, gliosis and Aß accumulation. Treatment with CDPPB for 28 days increased neuronal viability (32.2% increase in NeuN+ cells) and reduced gliosis in CA1 region (Iba-1+ area by 31.3% and GFAP+ area by 37.5%) in transgenic animals, without inducing hepatotoxicity. However, it did not reverse cognitive deficit. Despite a four-week treatment did not prevent memory loss in aged transgenic mice, CDPPB is protective against Aß stimulus. Therefore, this drug represents a potential candidate for further investigations as AD treatment.

15a Conferência Nacional de Saúde: um estudo de caso / 15th National Health Conference: a case study

Resumo O objetivo deste artigo é analisar a participação do Conselho Nacional na construção e realização da 15ª Conferência Nacional de Saúde (CNS), bem como os principais componentes desse evento, o desenho institucional, no que se refere a sua dinâmica participativa, e as propostas e diretrizes aprovadas, e relacionar esse fenômeno político à conjuntura brasileira. Este estudo de caso sobre a 15ª CNS teve como fonte de produção de dados entrevistas com 27 conselheiros nacionais e a revisão documental de atas, notícias e outras fontes do Conselho relacionadas à 15ª Conferência. O Conselho Nacional desenvolveu estratégias para politizar a elaboração das diretrizes e intensificou a participação da sociedade por meio das conferências livres. O debate em torno da saúde em 2015 envolveu milhares de pessoas no país - afinal, foram realizadas 4.706 conferências municipais, 26 estaduais, a conferência distrital e a nacional. As principais pautas da 15ª Conferência foram a defesa da democracia e o financiamento público da saúde. A 15ª CNS ainda prevaleceu com o formato burocrático. Além das inovações na forma das conferências, é necessário ampliar a permeabilidade dos tomadores de decisão à participação social e democratizar o processo de planejamento e a gestão em saúde.

Abstract This article aims to analyze the participation of the National Council in the construction and realization of the 15th National Health Conference (CNS), as well as the main components of this event, the institutional design regarding its participatory dynamics, and the approved proposals and guidelines, relating this political phenomenon to the Brazilian context. This case study on the 15th CNS had, as data sources, the interviews with 27 national counselors and the documentary review of minutes, news and other sources of the Council related to the 15th Conference. The National Council developed strategies to politicize the elaboration of guidelines and intensified society participation through free conferences. The Health debate in 2015 involved thousands of people in the country - after all, 4,706 municipal and 26 state, district and national conferences were held. The main agendas of the 15th Conference were the defense of democracy and the public financing of health. Nonetheless, the bureaucratic format still prevailed in the 15th CNS. In addition to innovations in the form of conferences, one must increase the permeability of decision-makers to social participation and democratize the health planning and management process.