Interleukin 1ß triggers synaptic and memory deficits in Herpes simplex virus type-1-infected mice by downregulating the expression of synaptic plasticity-related genes via the epigenetic MeCP2/HDAC4 complex.

Extensive research provides evidence that neuroinflammation underlies numerous brain disorders. However, the molecular mechanisms by which inflammatory mediators determine synaptic and cognitive dysfunction occurring in neurodegenerative diseases (e.g., Alzheimer's disease) are far from being fully understood. Here we investigated the role of interleukin 1ß (IL-1ß), and the molecular cascade downstream the activation of its receptor, to the synaptic dysfunction occurring in the mouse model of multiple Herpes simplex virus type-1 (HSV-1) reactivations within the brain. These mice are characterized by neuroinflammation and memory deficits associated with a progressive accumulation of neurodegenerative hallmarks (e.g., amyloid-ß protein and tau hyperphosphorylation). Here we show that mice undergone two HSV-1 reactivations in the brain exhibited increased levels of IL-1ß along with significant alterations of: (1) cognitive performances; (2) hippocampal long-term potentiation; (3) expression synaptic-related genes and pre- and post-synaptic proteins; (4) dendritic spine density and morphology. These effects correlated with activation of the epigenetic repressor MeCP2 that, in association with HDAC4, affected the expression of synaptic plasticity-related genes. Specifically, in response to HSV-1 infection, HDAC4 accumulated in the nucleus and promoted MeCP2 SUMOylation that is a post-translational modification critically affecting the repressive activity of MeCP2. The blockade of IL-1 receptors by the specific antagonist Anakinra prevented the MeCP2 increase and the consequent downregulation of gene expression along with rescuing structural and functional indices of neurodegeneration. Collectively, our findings provide novel mechanistic evidence on the role played by HSV-1-activated IL-1ß signaling pathways in synaptic deficits leading to cognitive impairment.

Cytoplasmic HDAC4 recovers synaptic function in the 3×Tg mouse model of Alzheimer's disease.

AIMS: Early dysfunction in Alzheimer's disease (AD) is characterised by alterations of synapse structure and function leading to dysmorphic neurites, decreased spine density, impaired synaptic plasticity and cognitive deficits. The class II member HDAC4, which recently emerged as a crucial factor in shaping synaptic plasticity and memory, was found to be altered in AD. We investigated how the modulation of HDAC4 may contribute to counteracting AD pathogenesis. METHODS: Using a cytoplasmic HDAC4 mutant (HDAC4SD ), we studied the recovery of synaptic function in hippocampal tissue and primary neurons from the triple-transgenic mouse model of AD (3×Tg-AD). RESULTS: Here, we report that in wild-type mice, HDAC4 is localised at synapses and interacts with postsynaptic proteins, whereas in the 3×Tg-AD, it undergoes nuclear import, reducing its interaction with synaptic proteins. Of note, HDAC4 delocalisation was induced by both amyloid-ß and tau accumulation. Overexpression of the HDAC4SD mutant in CA1 pyramidal neurons of organotypic hippocampal slices obtained from 3×Tg-AD mice increased dendritic length and promoted the enrichment of N-cadherin, GluA1, PSD95 and CaMKII proteins at the synaptic level compared with AD neurons transfected with the empty vector. Moreover, HDAC4 overexpression recovered the level of SUMO2/3ylation of PSD95 in AD hippocampal tissue, and in AD organotypic hippocampal slices, the HDAC4SD rescued spine density and synaptic transmission. CONCLUSIONS: These results highlight a new role of cytoplasmic HDAC4 in providing a structural and enzymatic regulation of postsynaptic proteins. Our findings suggest that controlling HDAC4 localisation may represent a promising strategy to rescue synaptic function in AD, potentially leading to memory improvement.

Estudo de avaliabilidade das ações para detecção precoce do câncer de mama na atenção primária / Evaluability study of actions for early detection of breast cancer in primary care

RESUMO O artigo tem como objetivo desenvolver um modelo avaliativo das ações de detecção precoce do câncer de mama na atenção primária. Trata-se de um estudo de avaliabilidade, realizado pelas etapas de análise documental, revisão de literatura e reunião de consenso para elaboração da matriz avaliativa. O resultado obtido foi o desenvolvimento da Matriz de Análise e Julgamento, composta por 14 indicadores, agregados em duas dimensões. A aplicação do modelo avaliativo permitirá a identificação das fragilidades e potencialidades das ações de detecção precoce do câncer de mama.

ABSTRACT The article aims to develop an evaluative model of actions for the early detection of breast cancer in primary care. This evaluability study was conducted through document analysis, literature review, and consensus meeting stages to prepare the evaluative matrix. The result was the development of the Analysis and Judgment Matrix, composed of 14 indicators aggregated into two dimensions. Applying the evaluative model will allow the identification of the weaknesses and strengths of actions for the early detection of breast cancer.

How Brazilian oral health care workers face COVID-19: surveillance, biosafety, and education strategies

Aim: To investigate surveillance, biosafety, and education strategies of Brazilian oral health care workers (OHCWs) during the first wave of the COVID-19 outbreak. Methods: This was a cross-sectional study covering OHCWs from a single multicenter research centre. A self-administered and validated online questionnaire was used for data collection, including the following variables: sociodemographic, medical history, biosafety, professional experience, surveillance, and education. Results: The sample consisted of 644 OHCWs (82.5% dentists, 13.2% dental assistants and 4.3% technicians), most without comorbidities (84.8%), from the public (51.7%) and private (48.3%) health systems, in 140 cities of a southern state. The most prominent measures of surveillance were waiting room distancing and visual alerts, symptom assessment, and availability of guidelines on COVID-19. Regarding biosafety measures, the lowest adherence was related to intraoral radiographs (2.7±1.4; 95%CI: 2.6­2.9), use of dental dams (2.1±1.4; 95%CI: 2.0­2.2), and availability of high-power suction systems (2.5±1.7; 95%CI: 2.3­2.6). Among OHCWs, 52.6% received guidance on measures to take during dental care in the workplace. Continuing education was mainly through documents from non-governmental health authorities (77.4%). Conclusion: Surveillance and biosafety measures were adopted, but activities that reduce the spread of aerosols had less adherence. These findings underscore the importance of considering dental practices, and surveillance and education strategies to formulate policies and relevant support to address health system challenges during the COVID-19 pandemic. A coordinated action of permanent education by policymakers is necessary

Percepção dos estudantes de odontologia sobre o abuso infantil na cidade de Florianópolis (SC), Brasil / Perception of dental students about child abuse in the city of Florianópolis (SC), Brazil

O abuso infantil é, ainda, um dos grandes problemas de saúde pública no Brasil e no mundo, sendo que em 2020, houve o registro de mais de 75 mil notificações no Brasil. É de suma importância que os profissionais de saúde, sobretudo, cirurgiões-dentistas, estejam capacitados para fazer a identificação e notificação de suspeitas e casos de abuso infantil. Esta pesquisa analisou a percepção dos estudantes de odontologia da Universidade Federal de Santa Catarina (UFSC) sobre o abuso infantil e instrução destes para a realização da notificação compulsória às autoridades na cidade de Florianópolis. Foi aplicado um questionário eletrônico com dezesseis questões abertas e fechadas, previamente estabelecidas pelos autores, tendo como base estudos anteriores sobre o tema. A amostra não-probabilística composta por 69 participantes de todas as fases do curso de graduação em odontologia da UFSC por meio de um estudo transversal. Mais de 97% (n=67) dos entrevistados afirmaram saber o que é abuso infantil, no entanto, aproximadamente 80% (n=54) afirmaram não saber proceder frente a um caso, cerca de 90% (n=62) afirmaram não conhecer a legislação sobre notificação compulsória e 80% (n=57) afirmaram haver interesse em buscar informações sobre o tema. É imprescindível que estudantes de odontologia e cirurgiões-dentistas sejam capazes não só identificar casos de abuso infantil, mas como proceder e mitigar o ciclo de violência no qual esta criança está inserida

Child abuse is still a major public health problem in Brazil and worldwide, with more than 75,000 notifications in Brazil in 2020. It is of utmost importance that health professionals, especially dentists, are trained to identify and report suspected and reported cases of child abuse. This study analyzed the perception of dental students at the Federal University of Santa Catarina (UFSC) about child abuse and their instruction to make the compulsory notification to the authorities in the city of Florianópolis. An electronic questionnaire with sixteen open and closed questions previously established by the authors based on previous studies on the subject was applied to a non-probabilistic sample consisting of 69 participants from all stages of the undergraduate dental course at UFSC. More than 97% (n=67) of the participants said they knew what child abuse was, however, approximately 80% (n=54) said they did not know how to proceed when faced with a case and about 90% (n=62) said they did not know the legislation about compulsory notification and 80% (n=57) said they were interested in seeking information on the subject. It is essential that dental students and dentists are able not only to identify cases of child abuse, but how to proceed and mitigate the cycle of violence in which this child is inserted

Acute restraint stress impairs histamine type 2 receptor ability to increase the excitability of medium spiny neurons in the nucleus accumbens.

Histamine, a monoamine implicated in stress-related arousal states, is synthesized in neurons exclusively located in the hypothalamic tuberomammillary nucleus (TMN) from where they diffusely innervate striatal and mesolimbic networks including the nucleus accumbens (NAc), a vital node in the limbic loop. Since histamine-containing TMN neuron output increases during stress, we hypothesized that exposure of mice to acute restrain stress (ARS) recruits endogenous histamine type 2 receptor (H2R) signaling in the NAc, whose activation increases medium spiny neurons (MSNs) intrinsic excitability via downregulation of A-type K+ currents. We employed an ARS paradigm in which mice were restrained for 120 min, followed by a 20-min recovery period, after which brain slices were prepared for ex vivo electrophysiology. Using whole-cell patch-clamp recordings, we found that pharmacological activation of H2R failed to affect MSN excitability and A-type K+ currents in mice that underwent ARS. Interestingly, in mice treated with H2R-antagonist prior to ARS paradigm, H2R activation increased evoked firing and decreased A-type K+ currents similarly to what observed in control mice. Furthermore, H2R-antagonist treatment ameliorated anxiety-like behavior in ARS mice. Together, our findings indicate that ARS paradigm recruits endogenous H2R signaling in MSNs and suggest the involvement of H2R signaling in stress-related motivational states.

Activation of histamine type 2 receptors enhances intrinsic excitability of medium spiny neurons in the nucleus accumbens.

Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, from where they project to many brain areas including the nucleus accumbens (NAc), a brain area that integrates diverse monoaminergic inputs to coordinate motivated behaviours. While the NAc expresses various histamine receptor subtypes, the mechanisms by which histamine modulates NAc activity are still poorly understood. Using whole-cell patch-clamp recordings, we found that pharmacological activation of histamine 2 (H2) receptors elevates the excitability of NAc medium spiny neurons (MSNs), while activation of H1 receptors failed to significantly affect MSN excitability. The evoked firing of MSNs increased after seconds of local H2 agonist administration and remained elevated for minutes. H2 receptor (H2R) activation accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, diminished action potential afterhyperpolarization and increased the action potential half-width. The increased excitability was protein kinase A-dependent and associated with decreased A-type K+ currents. In addition, selective pharmacological inhibition of the Kv4.2 channel, the main molecular determinant of A-type K+ currents in MSNs, mimicked and occluded the increased excitability induced by H2R activation. Our results indicate that histaminergic transmission in the NAc increases MSN intrinsic excitability through H2R-dependent modulation of Kv4.2 channels. Activation of H2R will significantly alter spike firing in MSNs in vivo, and this effect could be an important mechanism by which these receptors mediate certain aspects of goal-induced behaviours. KEY POINTS: Histamine is synthesized and released by hypothalamic neurons of the tuberomammillary nucleus and serves as a general modulator for whole-brain activity including the nucleus accumbens. Histamine receptors type 2 (HR2), which are expressed in the nucleus accumbens, couple to Gαs/off proteins which elevate cyclic adenosine monophosphate levels and activate protein kinase A. Whole-cell patch-clamp recordings revealed that H2R activation increased the evoked firing in medium spiny neurons of the nucleus accumbens via protein kinase A-dependent mechanisms. HR2 activation accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, diminished action potential medium after-hyperpolarization and increased the action potential half-width. HR2 activation also reduced A-type potassium current. Selective pharmacological inhibition of the Kv4.2 channel mimicked and occluded the increased excitability induced by H2R activation.

Access to high-priced medicines: inequalities in the organization and the results among Brazilian states. / Acesso a medicamentos de alto preço: desigualdades na organização e resultados entre estados brasileiros.

This case study aimed to characterize the Specialized Component of Pharmaceutical Services (CEAF) organization in four Brazilian states from diverse regions of the country. Data were collected with representatives of CEAF management from states in different regions, who answered a 21-question questionnaire on scope, organization, financing, hurdles, and facilitators. This information was complemented with data from national health surveys, DataSUS, the applied resources, and socioeconomic indicators. Differences were observed between states on issues such as the proportion of users and the decentralization of services. These characteristics seem to be related to the level of development concerning the socioeconomic indicators used. Advances in access to medicines were highlighted, despite the difficulties complying with the CEAF's objectives, such as insufficient resources, the qualification of human resources, and the provision of necessary visits and exams. The results point to advances, different forms of organization and highlight the need for more in-depth studies on the clinical and economic outcomes achieved as a strategy to outline solutions to achieve the comprehensive and equal care for users.

Este estudo de caso visou caracterizar a organização do Componente Especializado da Assistência Farmacêutica (CEAF) em quatro estados, de diferentes regiões do país. A coleta de dados foi realizada junto a representantes da gestão do CEAF, os quais responderam um questionário com 20 perguntas sobre: abrangência, organização, financiamento, barreiras e facilitadores. Essas informações foram complementadas com dados de inquéritos nacionais de saúde, do DataSUS, os valores investidos e indicadores socioeconômicos. Observaram-se diferenças entre os estados em questões como a proporção de usuários e a descentralização dos serviços. Estas características parecem estar relacionadas com o grau de desenvolvimento em termos dos indicadores socioeconômicos utilizados. Destacaram-se avanços no acesso a medicamentos, apesar das dificuldades para o cumprimento dos objetivos do CEAF, como a insuficiência de recursos, de qualificação da força de trabalho e da oferta de consultas e exames necessários. Os resultados indicam avanços, diferentes formas de organização e destacam a necessidade de estudos mais aprofundados relativos aos resultados clínicos e econômicos alcançados, como uma estratégia para traçar soluções para o atendimento integral e equânime dos usuários.

Acesso a medicamentos de alto preço: desigualdades na organização e resultados entre estados brasileiros / Access to high-priced medicines: inequalities in the organization and the results among Brazilian states

Resumo Este estudo de caso visou caracterizar a organização do Componente Especializado da Assistência Farmacêutica (CEAF) em quatro estados, de diferentes regiões do país. A coleta de dados foi realizada junto a representantes da gestão do CEAF, os quais responderam um questionário com 20 perguntas sobre: abrangência, organização, financiamento, barreiras e facilitadores. Essas informações foram complementadas com dados de inquéritos nacionais de saúde, do DataSUS, os valores investidos e indicadores socioeconômicos. Observaram-se diferenças entre os estados em questões como a proporção de usuários e a descentralização dos serviços. Estas características parecem estar relacionadas com o grau de desenvolvimento em termos dos indicadores socioeconômicos utilizados. Destacaram-se avanços no acesso a medicamentos, apesar das dificuldades para o cumprimento dos objetivos do CEAF, como a insuficiência de recursos, de qualificação da força de trabalho e da oferta de consultas e exames necessários. Os resultados indicam avanços, diferentes formas de organização e destacam a necessidade de estudos mais aprofundados relativos aos resultados clínicos e econômicos alcançados, como uma estratégia para traçar soluções para o atendimento integral e equânime dos usuários.

Abstract This case study aimed to characterize the Specialized Component of Pharmaceutical Services (CEAF) organization in four Brazilian states from diverse regions of the country. Data were collected with representatives of CEAF management from states in different regions, who answered a 21-question questionnaire on scope, organization, financing, hurdles, and facilitators. This information was complemented with data from national health surveys, DataSUS, the applied resources, and socioeconomic indicators. Differences were observed between states on issues such as the proportion of users and the decentralization of services. These characteristics seem to be related to the level of development concerning the socioeconomic indicators used. Advances in access to medicines were highlighted, despite the difficulties complying with the CEAF's objectives, such as insufficient resources, the qualification of human resources, and the provision of necessary visits and exams. The results point to advances, different forms of organization and highlight the need for more in-depth studies on the clinical and economic outcomes achieved as a strategy to outline solutions to achieve the comprehensive and equal care for users.

[Evaluability study of the Multicenter Program for Professional Qualification in Distance Home Care (PMQPAD)]. / Estudo de avaliabilidade do Programa Multicêntrico de Qualificação Profissional em Atenção Domiciliar a Distância (PMQPAD).

With the implementation of home care in the Brazilian Unified National Health System (SUS), the need to train administrators and health workers led to the creation of the Multicenter Program for Professional Qualification in Distance Home Care (PMQPAD) in a partnership between the SUS Open University and the General Coordinating Division for Home Care, of the Brazilian Ministry of Health. Through courses in specialization, improvement, and self-instruction, the program achieved wide capillarity and scope in the country, with nearly 300,000 enrollments across all states of Brazil. The current study aimed to structure a model to assess the PMQPAD through an evaluability study with participation by the program's administrators. We used the methodology developed by Thurston & Ramaliu, the stages of which allowed describing the program, representing it with a log frame model, and developing a evaluation matrix. We conducted document analysis, semi-structured interviews, and consensus workshops for the model's validation. The process resulted in the development of three evaluation matrices, one for each of the program's course modalities, with four analytical dimensions in common (Course characteristics and educational resources; Institutional aspects; Results; Impacts). The primary data sources for the evaluation indicators were the students, tutors, and administrators. The study drew on stakeholders' participation and proved appropriate for the development of the evaluation proposal. The results highlight the potential for use of evaluation matrices developed for the assessment of other distance training programs under the SUS.

Com a implantação da atenção domiciliar no âmbito do Sistema Único de Saúde (SUS), diante da necessidade de capacitação de gestores e profissionais, criou-se o Programa Multicêntrico de Qualificação Profissional em Atenção Domiciliar a Distância (PMQPAD) numa parceria entre a Universidade Aberta do SUS e a Coordenação Geral de Atenção Domiciliar do Ministério da Saúde. Por meio de cursos de especialização, aperfeiçoamento e autoinstrucionais, o programa teve grande capilaridade e alcance no país, com quase 300 mil matrículas distribuídas em todos os estados brasileiros. O objetivo do presente estudo foi estruturar um modelo avaliativo do PMQPAD, por meio de um estudo de avaliabilidade, com a participação dos gestores do programa. Foi utilizada a metodologia desenvolvida por Thurston & Ramaliu, cujas etapas permitiram descrever o programa, representá-lo por meio de um modelo lógico e desenvolver uma matriz avaliativa. Foram realizadas análise documental, entrevistas semiestruturadas e oficinas de consenso para validação do modelo. O processo resultou no desenvolvimento de três matrizes avaliativas, uma para cada modalidade de curso do programa, com quatro dimensões de análise em comum (Características do curso e recursos educacionais; Aspectos institucionais; Resultados; Impactos). Os indicadores avaliativos tiveram, como fontes de dados primários, os alunos, os tutores e os gestores do curso. O estudo contou com a participação dos stakeholders e mostrou-se apropriado para o desenvolvimento da proposta avaliativa. Destaca-se o potencial de utilização das matrizes avaliativas desenvolvidas para a avaliação de outros programas de formação a distância no âmbito do SUS.

Con la implantación de la atención domiciliaria en el ámbito del Sistema Único de Salud (SUS), ante la necesidad de la capacitación de gestores y profesionales, se creó el Programa Multicéntrico de Cualificación Profesional en Atención Domiciliaria a Distancia (PMQPAD), en una colaboración entre la Universidad Abierta del SUS y la Coordinación General de Atención Domiciliaria del Ministerio de Salud de Brasil. A través de cursos de especialización, perfeccionamiento y de autoaprendizaje, el programa tuvo una gran capilaridad y alcance en el país, con casi 300 mil matrículas, distribuidas por todos los estados brasileños. El objetivo del presente estudio fue estructurar un modelo evaluativo del PMQPAD, a través de un estudio de disponibilidad, con la participación de los gestores del programa. Se utilizó la metodología desarrollada por Thurston & Ramaliu, cuyas etapas permitieron describir el programa, representarlo a través de un modelo lógico, y desarrollar una matriz evaluativa. Se realizó un análisis documental, entrevistas semiestructuradas y talleres de consenso para la validación del modelo. El proceso resultó en el desarrollo de tres matrices evaluativas, una para cada modalidad de curso del programa, con cuatro dimensiones de análisis en común (Características del curso y recursos educacionales; Aspectos institucionales; Resultados; Impactos). Los indicadores evaluativos tuvieron como fuentes de datos primarios los alumnos, los tutores y los gestores del curso. El estudio contó con la participación de los stakeholders, y se mostró apropiado para el desarrollo de la propuesta evaluativa. Se destaca el potencial de utilización de las matrices evaluativas desarrolladas para la evaluación de otros programas de formación a distancia en el ámbito del SUS.

Connexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing.

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca2+) waves propagated from irradiated to bystander cells promoting intracellular Ca2+ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of apoptotic pathways. Combination treatment with S-nitrosoglutathione (GSNO), an endogenous nitric oxide (NO) donor that biases HCs towards the open state, greatly potentiated anti-tumor bystander killing via enhanced Ca2+ signaling, leading to a significant reduction of post-irradiation tumor mass. Our results demonstrate that HCs can be exploited to dramatically increase cytotoxic bystander effects and reveal a previously unappreciated role for HCs in tumor eradication promoted by PDT.

Epigenetic regulation of neural stem cells: The emerging role of nucleoporins.

Nucleoporins (Nups) are components of the nuclear pore complex that, besides regulating nucleus-cytoplasmic transport, emerged as a hub for chromatin interaction and gene expression modulation. Specifically, Nups act in a dynamic manner both at specific gene level and in the topological organization of chromatin domains. As such, they play a fundamental role during development and determination of stemness/differentiation balance in stem cells. An increasing number of reports indicate the implication of Nups in many central nervous system functions with great impact on neurogenesis, neurophysiology, and neurological disorders. Nevertheless, the role of Nup-mediated epigenetic regulation in embryonic and adult neural stem cells (NSCs) is a field largely unexplored and the comprehension of their mechanisms of action is only beginning to be unveiled. After a brief overview of epigenetic mechanisms, we will present and discuss the emerging role of Nups as new effectors of neuroepigenetics and as dynamic platform for chromatin function with specific reference to the biology of NSCs.

[Financing and management: the technical efficiency in public health expenditures of small-scale municipalities in the state of Santa Catarina]. / Financiamento e gestão: a eficiência técnica dos municípios catarinenses de pequeno porte nos gastos públicos com saúde.

In a context of budget constraints and fiscal austerity measures, the discussion of issues related to the efficient management of public resources is a major challenge. The scope of this study was to assess the technical efficiency of municipalities of the State of Santa Catarina in public health expenditures and its relationship with health management conditions in the years 2009 and 2015. In order to measure efficiency, the decision was made to use Data Envelopment Analysis. The G Index was used to analyze the spatial efficiency autocorrelation. For the evaluation of the conditions for health management, the model proposed by Calvo et al. was adopted. Of the total number of municipalities analyzed, 35.5% and 29% were considered efficient, for the years 2009 and 2015, respectively. The results suggest that there is no association between the conditions for health management and technical efficiency in the State of Santa Catarina. The study revealed the need to move forward in the quest for better results in terms of efficiency in the State of Santa Catarina, taking into consideration the spatial distribution of these results over the territory, focusing on clusters of inefficiency that may explain the poor performance in health of some regions of the state.

Em um contexto de restrição orçamentária e de medidas de austeridade fiscal, discutir aspectos relacionados à gestão eficiente dos recursos públicos é um desafio. O objetivo deste estudo foi avaliar a eficiência técnica de municípios catarinenses nos gastos públicos com saúde e sua relação com as condições para a gestão em saúde nos anos de 2009 e 2015. Para medir a eficiência, optou-se pela Análise Envoltória de Dados. O Índice G foi empregado para analisar a autocorrelação espacial da eficiência. Para a avaliação das condições para a gestão em saúde, adotou-se o modelo proposto por Calvo et al. Do total de municípios analisados, 35,5% e 29% foram considerados eficientes, respectivamente para os anos de 2009 e 2015. Os resultados sugerem não haver associação entre as condições para a gestão em saúde e a eficiência técnica no estado de Santa Catarina. O estudo revelou a necessidade de se avançar na busca por melhores resultados de eficiência em Santa Catarina, devendo ser considerada a distribuição espacial destes resultados sobre o território, com enfoque sobre os clusters de ineficiência que podem explicar o fraco desempenho em saúde de algumas regiões do estado.

Structure and work process for food and nutrition actions in Primary Health Care in Brazil, 2014. / Estrutura e processo de trabalho para as ações de alimentação e nutrição na Atenção Primária à Saúde no Brasil, 2014.

OBJECTIVE: To evaluate the conditions of structure and work process for food and nutrition actions in Primary Health Care in Brazil. METHODS: This was a cross-sectional study with secondary data from the Program for Primary Health Care Access and Quality Improvement. The proportions of Primary Health Care Center (PHCC) and health team adequacy were described according to organizational variables, using prevalence ratios and Poisson regression. RESULTS: 19,793 PHCCs and 24,549 teams were analyzed; 35.0% (n=6,928) of PHCCs were considered adequate in relation to structure and 7.9% (n=1,934) of the teams had adequate work process. Standing out in the analyses of association are PHCCs in the Southern region (44.7%) and teams in the Southeastern region (10.9%), in addition to municipalities with more than 300,000 inhabitants. CONCLUSION: The PHCCs and teams analyzed presented a low proportion of adequacy for structure and work process for food and nutrition actions.

Financiamento e gestão: a eficiência técnica dos municípios catarinenses de pequeno porte nos gastos públicos com saúde / Financing and management: the technical efficiency in public health expenditures of small-scale municipalities in the state of Santa Catarina

Resumo Em um contexto de restrição orçamentária e de medidas de austeridade fiscal, discutir aspectos relacionados à gestão eficiente dos recursos públicos é um desafio. O objetivo deste estudo foi avaliar a eficiência técnica de municípios catarinenses nos gastos públicos com saúde e sua relação com as condições para a gestão em saúde nos anos de 2009 e 2015. Para medir a eficiência, optou-se pela Análise Envoltória de Dados. O Índice G foi empregado para analisar a autocorrelação espacial da eficiência. Para a avaliação das condições para a gestão em saúde, adotou-se o modelo proposto por Calvo et al. Do total de municípios analisados, 35,5% e 29% foram considerados eficientes, respectivamente para os anos de 2009 e 2015. Os resultados sugerem não haver associação entre as condições para a gestão em saúde e a eficiência técnica no estado de Santa Catarina. O estudo revelou a necessidade de se avançar na busca por melhores resultados de eficiência em Santa Catarina, devendo ser considerada a distribuição espacial destes resultados sobre o território, com enfoque sobre os clusters de ineficiência que podem explicar o fraco desempenho em saúde de algumas regiões do estado.

Abstract In a context of budget constraints and fiscal austerity measures, the discussion of issues related to the efficient management of public resources is a major challenge. The scope of this study was to assess the technical efficiency of municipalities of the State of Santa Catarina in public health expenditures and its relationship with health management conditions in the years 2009 and 2015. In order to measure efficiency, the decision was made to use Data Envelopment Analysis. The G Index was used to analyze the spatial efficiency autocorrelation. For the evaluation of the conditions for health management, the model proposed by Calvo et al. was adopted. Of the total number of municipalities analyzed, 35.5% and 29% were considered efficient, for the years 2009 and 2015, respectively. The results suggest that there is no association between the conditions for health management and technical efficiency in the State of Santa Catarina. The study revealed the need to move forward in the quest for better results in terms of efficiency in the State of Santa Catarina, taking into consideration the spatial distribution of these results over the territory, focusing on clusters of inefficiency that may explain the poor performance in health of some regions of the state.

Structure and work process for the actions of food and nutrition in Primary Health Care in Brazil, 2014 / Estructura y proceso de trabajo para acciones de alimentación y nutrición en Atención Primaria de Salud en Brasil 2014 / Estrutura e processo de trabalho para as ações de alimentação e nutrição na Atenção Primária à Saúde no Brasil, 2014

Objective: To evaluate the conditions of structure and work process for food and nutrition actions in primary health care in Brazil. Methods: Cross-sectional study with secondary data from the Program for Improving Access and Quality in Primary Care. The proportions of adequacy of the Basic Health Units (UBS) and health teams were described according to organizational variables for the reason of the prevalence and Poisson Regression. Results: 19,793 UBS and 24,549 teams were analyzed; 35.0% (n=6.928) of the UBS were considered adequate for the structure and 7.9% (n=1,934) of the appropriate teams in the work process. In the association analyzes, the UBS in the South region (44.7%) and the teams in the Southeast region (10.9%) stand out, in addition to municipalities with more than 300 thousand inhabitants. Conclusion: The UBS and teams analyzed presented a low proportion of adquacy for structure and work process for the actions of food and nutrition.

Objetivo:  Avaliar as condições de estrutura e de processo de trabalho para as ações de alimentação e nutrição na Atenção Primária à Saúde, no Brasil. Métodos: Estudo transversal, sobre dados secundários do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica. Foram descritas as proporções de adequação das unidades básicas de saúde (UBS) e equipes de saúde segundo variáveis organizacionais, pela razão da prevalência e regressão de Poisson. Resultados: Foram analisadas 19.793 UBS e 24.549 equipes; 35,0% (n=6.928) das UBS mostraram-se adequadas na estrutura e 7,9% (n=1.934) das equipes adequadas ao processo de trabalho. Nas análises de associação, destacaram-se as UBS da região Sul (44,7%) e as equipes da região Sudeste (10,9%), além de municípios com mais de 300 mil habitantes. Conclusão: As UBS e equipes analisadas apresentaram baixas proporções de adequação de estrutura e de processo de trabalho para as ações de alimentação e nutrição.

Estrutura e processo de trabalho para as ações de alimentação e nutrição na Atenção Primária à Saúde no Brasil, 2014 / Estructura y proceso de trabajo para las acciones de alimentación y nutrición en la Atención Primaria de Salud en Brasil, 2014 / Structure and work process for food and nutrition actions in Primary Health Care in Brazil, 2014

Objetivo: Avaliar as condições de estrutura e de processo de trabalho para as ações de alimentação e nutrição na Atenção Primária à Saúde, no Brasil. Métodos: Estudo transversal, sobre dados secundários do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica. Foram descritas as proporções de adequação das unidades básicas de saúde (UBS) e equipes de saúde segundo variáveis organizacionais, pela razão da prevalência e regressão de Poisson. Resultados: Foram analisadas 19.793 UBS e 24.549 equipes; 35,0% (n=6.928) das UBS mostraram-se adequadas na estrutura e 7,9% (n=1.934) das equipes adequadas ao processo de trabalho. Nas análises de associação, destacaram-se as UBS da região Sul (44,7%) e as equipes da região Sudeste (10,9%), além de municípios com mais de 300 mil habitantes. Conclusão: As UBS e equipes analisadas apresentaram baixas proporções de adequação de estrutura e de processo de trabalho para as ações de alimentação e nutrição.

Objetivo: Evaluar las condiciones de estructura y proceso de trabajo de las acciones de alimentación y nutrición en la Atención Primaria de Salud en Brasil. Métodos: Estudio transversal con datos del Programa de Mejoramiento del Acceso y la Calidad en la Atención Primaria. Se describieron las proporciones de adecuación de las Unidades Básicas de Salud (UBS) y equipos de salud según variables organizacionales por la razón de prevalencia y regresión de Poisson. Resultados: Se analizaron 19.793 UBS y 24.549 equipos. El 35,0% (n=6.928) de las UBS se consideraron adecuadas en la estructura y el 7,9% (n=1.934) de los equipos adecuados al proceso de trabajo. En los análisis asociativos se destacaron las UBS de la región Sur (44,7%) y los equipos de la región Sudeste (10,9%), además de los municipios con más de 300 mil habitantes. Conclusión: Las UBS y los equipos analizados presentaron bajas proporciones de adecuación para la estructura y el proceso de trabajo para las acciones de alimentación y nutrición.

Objective: To evaluate the conditions of structure and work process for food and nutrition actions in Primary Health Care in Brazil. Methods: This was a cross-sectional study with secondary data from the Program for Primary Health Care Access and Quality Improvement. The proportions of Primary Health Care Center (PHCC) and health team adequacy were described according to organizational variables, using prevalence ratios and Poisson regression. Results: 19,793 PHCCs and 24,549 teams were analyzed; 35.0% (n=6,928) of PHCCs were considered adequate in relation to structure and 7.9% (n=1,934) of the teams had adequate work process. Standing out in the analyses of association are PHCCs in the Southern region (44.7%) and teams in the Southeastern region (10.9%), in addition to municipalities with more than 300,000 inhabitants. Conclusion: The PHCCs and teams analyzed presented a low proportion of adequacy for structure and work process for food and nutrition actions.

Estudo de avaliabilidade do Programa Multicêntrico de Qualificação Profissional em Atenção Domiciliar a Distância (PMQPAD) / Evaluability study of the Multicenter Program for Professional Qualification in Distance Home Care (PMQPAD) / Estudio de disponibilidad del Programa Multicéntrico de Cualificación Profesional en la Atención Domiciliaria a Distancia (PMQPAD)

Resumo: Com a implantação da atenção domiciliar no âmbito do Sistema Único de Saúde (SUS), diante da necessidade de capacitação de gestores e profissionais, criou-se o Programa Multicêntrico de Qualificação Profissional em Atenção Domiciliar a Distância (PMQPAD) numa parceria entre a Universidade Aberta do SUS e a Coordenação Geral de Atenção Domiciliar do Ministério da Saúde. Por meio de cursos de especialização, aperfeiçoamento e autoinstrucionais, o programa teve grande capilaridade e alcance no país, com quase 300 mil matrículas distribuídas em todos os estados brasileiros. O objetivo do presente estudo foi estruturar um modelo avaliativo do PMQPAD, por meio de um estudo de avaliabilidade, com a participação dos gestores do programa. Foi utilizada a metodologia desenvolvida por Thurston & Ramaliu, cujas etapas permitiram descrever o programa, representá-lo por meio de um modelo lógico e desenvolver uma matriz avaliativa. Foram realizadas análise documental, entrevistas semiestruturadas e oficinas de consenso para validação do modelo. O processo resultou no desenvolvimento de três matrizes avaliativas, uma para cada modalidade de curso do programa, com quatro dimensões de análise em comum (Características do curso e recursos educacionais; Aspectos institucionais; Resultados; Impactos). Os indicadores avaliativos tiveram, como fontes de dados primários, os alunos, os tutores e os gestores do curso. O estudo contou com a participação dos stakeholders e mostrou-se apropriado para o desenvolvimento da proposta avaliativa. Destaca-se o potencial de utilização das matrizes avaliativas desenvolvidas para a avaliação de outros programas de formação a distância no âmbito do SUS.

Abstract: With the implementation of home care in the Brazilian Unified National Health System (SUS), the need to train administrators and health workers led to the creation of the Multicenter Program for Professional Qualification in Distance Home Care (PMQPAD) in a partnership between the SUS Open University and the General Coordinating Division for Home Care, of the Brazilian Ministry of Health. Through courses in specialization, improvement, and self-instruction, the program achieved wide capillarity and scope in the country, with nearly 300,000 enrollments across all states of Brazil. The current study aimed to structure a model to assess the PMQPAD through an evaluability study with participation by the program's administrators. We used the methodology developed by Thurston & Ramaliu, the stages of which allowed describing the program, representing it with a log frame model, and developing a evaluation matrix. We conducted document analysis, semi-structured interviews, and consensus workshops for the model's validation. The process resulted in the development of three evaluation matrices, one for each of the program's course modalities, with four analytical dimensions in common (Course characteristics and educational resources; Institutional aspects; Results; Impacts). The primary data sources for the evaluation indicators were the students, tutors, and administrators. The study drew on stakeholders' participation and proved appropriate for the development of the evaluation proposal. The results highlight the potential for use of evaluation matrices developed for the assessment of other distance training programs under the SUS.

Resumen: Con la implantación de la atención domiciliaria en el ámbito del Sistema Único de Salud (SUS), ante la necesidad de la capacitación de gestores y profesionales, se creó el Programa Multicéntrico de Cualificación Profesional en Atención Domiciliaria a Distancia (PMQPAD), en una colaboración entre la Universidad Abierta del SUS y la Coordinación General de Atención Domiciliaria del Ministerio de Salud de Brasil. A través de cursos de especialización, perfeccionamiento y de autoaprendizaje, el programa tuvo una gran capilaridad y alcance en el país, con casi 300 mil matrículas, distribuidas por todos los estados brasileños. El objetivo del presente estudio fue estructurar un modelo evaluativo del PMQPAD, a través de un estudio de disponibilidad, con la participación de los gestores del programa. Se utilizó la metodología desarrollada por Thurston & Ramaliu, cuyas etapas permitieron describir el programa, representarlo a través de un modelo lógico, y desarrollar una matriz evaluativa. Se realizó un análisis documental, entrevistas semiestructuradas y talleres de consenso para la validación del modelo. El proceso resultó en el desarrollo de tres matrices evaluativas, una para cada modalidad de curso del programa, con cuatro dimensiones de análisis en común (Características del curso y recursos educacionales; Aspectos institucionales; Resultados; Impactos). Los indicadores evaluativos tuvieron como fuentes de datos primarios los alumnos, los tutores y los gestores del curso. El estudio contó con la participación de los stakeholders, y se mostró apropiado para el desarrollo de la propuesta evaluativa. Se destaca el potencial de utilización de las matrices evaluativas desarrolladas para la evaluación de otros programas de formación a distancia en el ámbito del SUS.

Análise dos instrumentos de gestão elaborados pelas Secretarias Municipais de Saúde de Santa Catarina no período de 2014 a 2017 / Analysis of management tools elaborated by the Municipal Health Departments of Santa Catarina from 2014 to 2017

RESUMO Os instrumentos de gestão foram instituídos no Sistema Único de Saúde como ferramentas norteadoras da gestão, assegurando a participação social na sua elaboração e apreciação. O Plano de Saúde, a Programação Anual de Saúde (PAS) e o Relatório Anual de Gestão (RAG) devem ser elaborados conforme estrutura e prazos definidos pelo Sistema de Planejamento do SUS. Considerando sua importância, o objetivo deste estudo foi analisar a estrutura mínima dos instrumentos de gestão elaborados pelas Secretarias Municipais de Saúde do estado de Santa Catarina. Trata-se de uma pesquisa exploratória, quantitativa, realizada por meio de análise documental. Foram analisados o Plano Municipal de Saúde de 2014 a 2017; a PAS e o RAG referentes ao ano de 2017, anexados ao Sistema de Apoio à Construção do Relatório de Gestão. No total, 288 municípios possuíam o PMS, e, destes, 136 a estrutura mínima. Quanto ao RAG, 248 municípios apresentaram o instrumento, dos quais, 125 possuíam a PAS. Identificou-se que a maior parte dos municípios não construiu adequadamente os instrumentos de gestão ou não os enviou nos prazos estabelecidos. A falta de resoluções de aprovação dos instrumentos por parte dos Conselhos de Saúde denota a fragilidade da participação social na construção e no acompanhamento da execução desses instrumentos.

ABSTRACT The management tools were established in the Unified Health System as guiding management tools, ensuring social participation in its elaboration and appreciation. The Health Plan, the Annual Health Schedule (AHS) and the Annual Health Report (AHR) must be prepared according to the structure and deadlines defined in the SUS Planning System. Considering its importance, the objective of this study was to analyze the minimum structure of the management tools elaborated by the Municipal Health Departments of the state of Santa Catarina. This is an exploratory, quantitative research, carried out through document analysis. The Municipal Health Plan from 2014 to 2017; the AHS and the AHR, relating to the year 2017 were analyzed, attached to the Management Report Construction Support System. In total, 288 counties had the MHP and, of these, 136 had the minimum structure. Regarding the AHR, 248 cities presented the tool, of which 125 had the AHS. It was identified that most cities did not properly build management tools or sent them within the set deadlines. The lack of resolutions approving the instruments by the Health Councils indicates the fragility of social participation in the construction and monitoring of the implementation of these tools.

Chronic mild stress alters synaptic plasticity in the nucleus accumbens through GSK3ß-dependent modulation of Kv4.2 channels.

Although major depressive disorder (MDD) is highly prevalent, its pathophysiology is poorly understood. Recent evidence suggests that glycogen-synthase kinase 3ß (GSK3ß) plays a key role in memory formation, yet its role in mood regulation remains controversial. Here, we investigated whether GSK3ß activity in the nucleus accumbens (NAc) is associated with depression-like behaviors and synaptic plasticity. We performed whole-cell patch-clamp recordings of medium spiny neurons (MSNs) in the NAc and determined the role of GSK3ß in spike timing-dependent long-term potentiation (tLTP) in the chronic unpredictable mild stress (CUMS) mouse model of depression. To assess the specific role of GSK3ß in tLTP, we used in vivo genetic silencing by an adeno-associated viral vector (AAV2) short hairpin RNA against GSK3ß. In addition, we examined the role of the voltage-gated potassium Kv4.2 subunit, a molecular determinant of A-type K+ currents, as a potential downstream target of GSK3ß. We found increased levels of active GSK3ß and augmented tLTP in CUMS mice, a phenotype that was prevented by selective GSK3ß knockdown. Furthermore, knockdown of GSK3ß in the NAc ameliorated depressive-like behavior in CUMS mice. Electrophysiological, immunohistochemical, biochemical, and pharmacological experiments revealed that inhibition of the Kv4.2 channel through direct phosphorylation at Ser-616 mediated the GSK3ß-dependent tLTP changes in CUMS mice. Our results identify GSK3ß regulation of Kv4.2 channels as a molecular mechanism of MSN maladaptive plasticity underlying depression-like behaviors and suggest that the GSK3ß-Kv4.2 axis may be an attractive therapeutic target for MDD.