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The recently proposed nonadditive stochastic model (NSM) offers a coherent physical interpretation for diffusive phenomena in glass-forming systems. This model presents nonexponential relationships between viscosity, activation energy, and temperature, characterizing the non-Arrhenius behavior observed in supercooled liquids. In this work, we fit the NSM viscosity equation to experimental temperature-dependent viscosity data corresponding to 25 glass-forming liquids and compare the fit parameters with those obtained using the Vogel-Fulcher-Tammann (VFT), Avramov-Milchev (AM), and Mauro-Yue-Ellison-Gupta-Allan (MYEGA) models. The results demonstrate that the NSM provides an effective fitting equation for modeling viscosity experimental data in comparison with other established models (VFT, AM, and MYEGA), characterizing the activation energy in fragile liquids, presenting a reliable indicator of the degree of fragility of the glass-forming liquids.
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The design of complex health systems interventions, such as pay for performance (P4P), can be critical to determining such programmes' success. In P4P programmes, the design of financial incentives is crucial in shaping how these programmes work. However, the design of such schemes is usually homogenous across providers within a given scheme. Consequently, there is a limited understanding of the strengths and weaknesses of P4P design elements from the implementers' perspective. This study takes advantage of the unique context of Brazil, where municipalities adapted the federal incentive design, resulting in variations in incentive design across municipalities. The study aims to understand why municipalities in Brazil chose certain P4P design features, the associated challenges and the local adaptations made to address problems in scheme design. This study was a multiple case study design relying on qualitative data from 20 municipalities from two states in Northeastern Brazil. We conducted two key informant interviews with municipal-level stakeholders and focus group discussions with primary care providers. We also reviewed municipal Primary Care Access and Quality laws in each municipality. We found substantial variation in the design choices made by municipalities regarding 'who was incentivized', the 'payment size' and 'frequency'. Design choices affected relationships within municipalities and within teams. Challenges were chiefly associated with fairness relating to 'who received the incentive', 'what is incentivized' and the 'incentive size'. Adaptations were made to improve fairness, mostly in response to pressure from the healthcare workers. The significant variation in design choices across municipalities and providers' response to them highlights the importance of considering local context in the design and implementation of P4P schemes and ensuring flexibility to accommodate local preferences and emerging needs. Attention is needed to ensure that the choice of 'who is incentivized' and the 'size of incentives' are inclusive and fair and the allocation and 'use of funds' are transparent.
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Atención Primaria de Salud , Reembolso de Incentivo , Brasil , Humanos , Atención Primaria de Salud/economía , Grupos Focales , Ciudades , Accesibilidad a los Servicios de Salud , Investigación Cualitativa , Entrevistas como Asunto , Gobierno Local , Calidad de la Atención de Salud , MotivaciónRESUMEN
Studies reporting the expression of hepatitis A virus (HAV) structural proteins, specifically recombinant VP1-2A containing an immunogenic activity, use the Escherichia coli system. Recombinant HAV proteins may represent a source of less expensive antigens for application in different diagnostic platforms. However, the formation of insoluble aggregates is an obstacle to obtaining large amounts of HAV proteins in their native form. To overcome this obstacle, some approaches were applied in this study to improve purification, solubility, and protein expression levels. Critical properties were evaluated. The introduction of another insertion codon to increase the protein concentration and vector activity was observed and verified by SDS-PAGE. The expression was established with 0.4 mM IPTG for 4 h at 37 °C. The VP1 protein was partially soluble at an isoeletric point (pI) of 6.45. The majority of HAV VP1-2A proteins measured 45.19 kDa in size and had a homogeneity of 53.58%. Multi-antigen print immunoassay (MAPIA) showed antigenicity at different HAV VP1-2A concentrations, and microsphere-based immunoassays showed a specificity of 100% and a sensitivity of 84%. HAV VP1-2A was characterized using different sensitivity methods to prove its biological activity, indicating its use as a tool for the diagnosis of Hepatitis A virus infection.
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Virus de la Hepatitis A , Hepatitis A , Humanos , Virus de la Hepatitis A/genética , Proteínas Recombinantes , Hepatitis A/diagnósticoRESUMEN
O estudo buscou compreender a influência da estratégia do Pay for Performance (P4P), por meio do Programa Nacional de Melhoria do Acesso e Qualidade da Atenção Básica (PMAQ-AB), na atuação do(a)s trabalhadore(a)s. Trata-se de um estudo de caso qualitativo realizado com o(a)s trabalhadore(a)s das Estratégias de Saúde da Família. A análise foi realizada mediante a técnica de construção de narrativas. Constatou-se que o P4P contribuiu para qualificação do processo de trabalho, ao mesmo tempo que estimulou competição e conflito entre as equipes, aflorando sentimentos de culpa e injustiça e, devido à precarização do trabalho, o estímulo financeiro se descaracteriza, tornando-se complemento salarial. Problemas macroestruturais afetam as condições de trabalho e a motivação do(a)s trabalhadore(a)s, de modo que modelos de incentivo financeiro, isoladamente, não são suficientes para reverter tal cenário.
This study sought to understand the influence of pay-for-performance (P4P) on worker performance using data from the National Program for Improving Primary Care Access and Quality (PMAQ-AB). We conducted a qualitative case study with professionals working in family health strategy teams. The data were analyzed using the narrative construction technique. The findings show that P4P contributed to the improvement of work processes, while at the same time stimulating competition and conflict between the teams, causing feelings of guilt and injustice. However, the original purpose of the financial incentive is defeated due to poor working terms and conditions, becoming akin to a salary supplement. Macrostructural problems affect working conditions and worker motivation, showing that financial incentive models alone are not sufficient to reverse this situation.
El estudio buscó comprender la influencia de la estrategia Pay for Performance (P4P), por medio del Programa de Mejora del Acceso y Calidad de la Atención Básica (Pmaq-AB), en la actuación de los trabajadores y las trabajadoras. Se trata de un estudio de caso, cualitativo, realizado con los trabajadores y las trabajadoras de las Estrategias de Salud de la Familia. El análisis se realizó mediante la construcción de narrativas. Se constató que el P4P contribuyó para la calificación del proceso de trabajo, al mismo tiempo que incentivó competencia y conflicto entre los equipos, haciendo aflorar los sentimientos de culpa e injusticia y, debido a la precarización del trabajo, el incentivo financiero se descaracteriza pasando a ser complemento salarial. Problemas macroestructurales afectan las condiciones de trabajo y la motivación de los trabajadores y de las trabajadoras, de modo que los modelos de incentivo económico, aisladamente, no son suficientes para revertir ese escenario.
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Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
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Pay-for-performance (P4P) has been widely applied in OECD countries to improve the quality of both primary and secondary care, and is increasingly being implemented in low- and middle-income countries. In 2011, Brazil introduced one of the largest P4P schemes in the world, the National Programme for Improving Primary Care Access and Quality (PMAQ). We critically assess the design of PMAQ, drawing on a comparison with England's quality and outcome framework which, like PMAQ, was implemented at scale relatively rapidly within a nationalised health system. A key feature of PMAQ was that payment was based on the performance of primary care teams but rewards were given to municipalities, who had autonomy in how the funds could be used. This meant the incentives felt by family health teams were contingent on municipality decisions on whether to pass the funds on as bonuses and the basis upon which they allocated the funds between and within teams. Compared with England's P4P scheme, performance measurement under PMAQ focused more on structural rather than process quality of care, relied on many more indicators, and was less regular. While PMAQ represented an important new funding stream for primary health care, our review suggests that theoretical incentives generated were unclear and could have been better structured to direct health providers towards improvements in quality of care.
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Calidad de la Atención de Salud , Reembolso de Incentivo , Humanos , Brasil , Atención Primaria de Salud , InglaterraRESUMEN
RESUMO Esta pesquisa teve como objetivo compreender como as teorias que sustentam a chamada epistemologia da prática se fazem presentes no debate acadêmico sobre a formação de professores de Educação Física. Trata-se de uma pesquisa do tipo bibliográfica, que buscou investigar as produções acadêmicas stricto sensu, selecionadas no Catálogo de Teses e Dissertações da Capes, produzidas nos últimos dez anos e que versam sobre formação de professores de Educação Física. Apesar de identificarmos produções onde o caráter ideológico de tais teorias é questionado, a análise nos permitiu compreender que as teorias que sustentam a epistemologia da prática se fazem presentes na maior parte das produções acadêmicas, reforçando a finalidade pragmática sobre o trabalho docente.
ABSTRACT This research aimed to understand how the theories that support the so-called epistemology of practice are present in the academic debate on the training of Physical Education teachers. This is a bibliographical research, which sought to investigate stricto sensu academic productions, selected in the Catalog of theses and dissertations of Capes, produced in the last ten years and that deal with the training of Physical Education teachers. Despite identifying productions where the ideological character of such theories is questioned, the analysis allowed us to understand that the theories that support the epistemology of practice are present in most academic productions, reinforcing the pragmatic purpose of teaching work.
RESUMEN Esta investigación tuvo como objetivo comprender cómo las teorías que sustentan la llamada epistemología de la práctica están presentes en el debate académico sobre la formación de profesores de Educación Física. Se trata de una investigación bibliográfica, que buscó investigar producciones académicas estricto sensu, seleccionadas en el Catálogo de tesis y disertaciones de la Capes, producidas en los últimos diez años y que versan sobre la formación de profesores de Educación Física. A pesar de identificar producciones donde se cuestiona el carácter ideológico de tales teorías, el análisis permitió comprender que las teorías que sustentan la epistemología de la práctica están presentes en la mayoría de las producciones académicas, reforzando el propósito pragmático del trabajo docente.
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Este artigo analisa a execução do PMAQ-AB a partir de sua contextualização em um cenário político nacional de profundas transformações, desde o reformismo fraco que promoveu lenta extensão de direitos até o contrarreformismo forte da restauração neoliberal. Para debater os elementos relacionados ao trabalho e às disputas pela distribuição dos recursos públicos, foi realizado estudo de caso com trabalhadores, gestores e conselheiros de saúde em duas capitais do nordeste brasileiro. Os resultados evidenciam o acirramento do conflito distributivo e o resultado desfavorável aos trabalhadores no contexto pós-golpe parlamentar de 2016. As dinâmicas locais expõem processos de contração salarial e individualização das relações de trabalho e a reafirmação da meritocracia como justificativa ideológica da precarização. A isso, trabalhadores se contrapõem pela reafirmação de sua condição coletiva de classe, em favor de benefícios derivados do PMAQ, como recomposição salarial para todos.(AU)
Este artículo analiza la realización del PMAQ-AB a partir de su contextualización en un escenario político nacional de profundas transformaciones, desde el reformismo débil que promovió una lenta extensión de derechos contra el reformismo fuerte de la restauración neoliberal. Para discutir los elementos relacionados al trabajo y a las disputas por la distribución en los recursos públicos se realizó un estudio de caso con trabajadores, gestores y consejeros de salud en dos capitales del nordeste brasileño. Los resultados ponen en evidencia el recrudecimiento del conflicto distributivo y el resultado desfavorable para los trabajadores en el contexto post-golpe parlamentario de 2016. Las dinámicas locales exponen procesos de contracción salarial e individualización de las relaciones de trabajo y la reafirmación de la meritocracia como justificativa ideológica de la precarización. A eso se contraponen los trabajadores por medio de la reafirmación de su condición colectiva de clase, en favor del beneficio derivado del PMAQ con la recomposición salarial para todos.(AU)
This article analyzes the implementation of the Program for Improving Access and Quality of Primary Care (PMAQ-AB) in the context of a national political scenario of deep transformations, from the weak reformism that promoted slow extension of rights to the strong counter-reformism of neoliberal restoration. It is a case study with health workers, managers, and counselors in two capital cities in northeastern Brazil, discussing matters of work and distributive disputes of public resources. Results show the intensification of these conflicts in health and the unfavorable outcome for workers after the parliamentary coup in 2016 political context. Local dynamics expose the wage contraction and individualization of labor relations and the reassertion of meritocracy as an ideological ground for precariousness. Workers oppose this, reaffirming their collective class condition, favoring the benefit derived from PMAQ for fully regaining their group wages.(AU)
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INTRODUCTION: Occult breast carcinoma (OBC) is a rare entity and therefore generates discussion regarding diagnosis, approach, and prognosis. This article aims to present a case of OBC and reviews some concepts discussed in the literature. PRESENTATION OF CASE: 43-year-old woman with right axillary adenopathies, without further complaints, whose biopsy shows a lymph node metastasis from invasive ductal carcinoma of the breast. Breast study, breast RMI and FDG-PET did not identify the primary tumour. As decided by a multidisciplinary team, the patient underwent neoadjuvant chemotherapy, axillary surgery, breast radiotherapy and hormone therapy. Four years after surgery, the patient has no evidence of the primary tumour and no axillary recurrence. DISCUSSION: OBC was described in 1907. Although the best therapeutic approach is widely discussed in the literature, it is consensual that as long as the existence of a primary tumour is excluded by breast MRI, the conservative approach (excision of axillary adenopathy and breast and axillary radiotherapy) is more advocated. CONCLUSION: Breast cancer must be considered in the differential diagnosis of a patient with axillary lymphadenopathy. The conservative approach of OBC is the preferred since breast MRI does not identify any suspicious lumps.
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Infections caused by SARS-CoV-2 induce a severe acute respiratory syndrome called COVID-19 and have led to more than six million deaths worldwide. Vaccination is the most effective preventative measure, and cellular and humoral immunity is crucial to developing individual protection. Here, we aim to investigate hybrid immunity against SARS-CoV-2 triggered by the ChAadOx1 nCoV-19 vaccine in a Brazilian cohort. We investigated the immune response from ChAadOx1 nCoV-19 vaccination in naïve (noCOVID-19) and previously infected individuals (COVID-19) by analyzing levels of D-dimers, total IgG, neutralizing antibodies (Nabs), IFN-γ (interferon-γ) secretion, and immunophenotyping of memory lymphocytes. No significant differences in D-dimer levels were observed 7 or 15 days after vaccination (DAV). All vaccinated individuals presented higher levels of total IgG or Nabs with a positive correlation (R = 0.88). Individuals in the COVID-19 group showed higher levels of antibody and memory B cells, with a faster antibody response starting at 7 DAV compared to noCOVID-19 at 15 DAV. Further, ChAadOx1 nCoV-19 vaccination led to enhanced IFN-γ production (15 DAV) and an increase in activated T CD4+ naïve cells in noCOVID-19 individuals in contrast with COVID-19 individuals. Hence, our data support that hybrid immunity triggered by ChAadOx1 nCoV-19 vaccination is associated with enhanced humoral response, together with a balanced cellular response.
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COVID-19 , Vacunas Virales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Humanos , Inmunidad Celular , Inmunidad Humoral , Inmunoglobulina G , Interferón gamma , SARS-CoV-2 , VacunaciónRESUMEN
The depth and versatility of siRNA technologies enable their use in disease targets that are undruggable by small molecules or that seek to achieve a refined turn-off of the genes for any therapeutic area. Major extracellular barriers are enzymatic degradation of siRNAs by serum endonucleases and RNAases, renal clearance of the siRNA delivery system, the impermeability of biological membranes for siRNA, activation of the immune system, plasma protein sequestration, and capillary endothelium crossing. To overcome the intrinsic difficulties of the use of siRNA molecules, therapeutic applications require nanometric delivery carriers aiming to protect double-strands and deliver molecules to target cells. This review discusses the history of siRNAs, siRNA design, and delivery strategies, with a focus on progress made regarding siRNA molecules in clinical trials and how siRNA has become a valuable asset for biopharmaceutical companies.
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Enfermedades del Cabello , Liquen Plano , Alopecia/complicaciones , Fibrosis , Humanos , MasculinoRESUMEN
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is considered a public health problem, mainly in severely obese patients. The aim of the present study was to investigate different biochemical-based scores available and determine which one could best serve as an NAFLD predicting tool in a severely obese population. METHODS: This was a cross-sectional study involving severely obese patients. All patients were evaluated with serum laboratory parameters for 1 week before biopsy, and all patients were treated with intraoperative liver biopsy, during bariatric surgery. RESULTS: A total of 143 severely obese patients were included. The median body mass index (BMI) was 48 kg/m2 (35-65). Diabetes mellitus was present in 36%, and steatosis was present in 93% (severe steatosis in 20%). Only aspartate transaminase (AST) to platelet ratio index (APRI=0.65 (95% CI: 0.55-0.8) and homeostatic model assessment for insulin resistance (HOMA-IR=0.7 (95% CI: 0.58-0.82) showed significant capacity for the prediction of severe steatosis. Hepatic steatosis index (HSI), NAFLD fibrosis score (NAFLDS), alanine aminotransferase (ALT)/AST, and fibrosis-4 (FIB-4) were not able to correctly predict severe steatosis on liver biopsy. APRI showed high specificity of 82% and low sensitivity of 54%. In contrast, HOMA-IR showed high sensitivity of 84% and low specificity of 48%. CONCLUSIONS: NAFLDS, FIB-4, AST/ALT, and HSI have no utility for the evaluation of severe steatosis in severely obese patients. Diabetes and insulin-resistance-related biochemical assessments, such as HOMA-IR, can be used as good screening tools for severe steatosis in these patients. APRI score is the most specific biochemical diagnostic tool for steatosis in severely obese patients and can help clinicians to decide the need for bariatric or metabolic surgery.
OBJETIVOS: A doença hepática gordurosa não-alcoólica já é considerada um problema de saúde pública, principalmente em pacientes com obesidade severa. O objetivo do presente estudo foi investigar os diferentes escores de bioquímiosa disponíveis e determinar qual deles poderia servir melhor como uma ferramenta de avaliação da NAFLD em uma população de obesos. MÉTODOS: Este é um estudo transversal de pacientes obesos. Todos os pacientes foram avaliados com parâmetros laboratoriais séricos 1 semana antes da biópsia e todos os pacientes foram submetidos a biópsia hepática intra-operatória, durante a cirurgia bariátrica. RESULTADOS: Cento e quarenta e três pacientes obesos foram incluídos. Apenas APRI (0,65; IC 95%: 0,55 a 0,8) e HOMA-IR (0,7; IC 95%: 0,58 a 0,82) mostraram capacidade significativa de predição de esteatose grave. HSI, NALFDS, ALS / AST e FIB-4 não foram capazes de prever corretamente esteatose grave na biópsia hepática. APRI mostrou alta especificidade (82%) e baixa sensibilidade (54%). Em contraste, o HOMA-IR apresentou alta sensibilidade (84%) e baixa especificidade (48%). CONCLUSÃO: O NALFDS, FIB-4, AST / ALT e HSI não têm utilidade para avaliação de esteatose grave em pacientes com obesidade severa. Diabetes e avaliação bioquímica relacionada à resistência à insulina, como o HOMA-IR, podem ser empregados como boas ferramentas de rastreamento para esteatose grave em tais pacientes. O escore APRI é a ferramenta diagnóstica bioquímica mais específica para esteatose em pacientes com obesidade severa e pode ser empregado, por equipes médicas, para auxiliar na indicação de cirurgia bariátrica ou metabólica.
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Cirugía Bariátrica , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Estudios Transversales , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , ObesidadRESUMEN
A regionalização da saúde se destaca noâ¯Sistema Único de Saúde como importante estratégia para lidar com as desigualdades regionais vividas no território brasileiro. O estado da Bahia foi pioneiroâ¯na descentralização administrativaâ¯estadual no setor da saúde, alémâ¯deâ¯ter sua secretaria estadual protagonista no planejamento de redes e fluxos assistenciaisâ¯regionais. Esteâ¯artigo apresenta discussões sobre oâ¯processo de regionalização da saúde na Bahia, após a reforma administrativa, com a extinção das diretorias regionais e a criação dos núcleos regionais. Foram realizadas entrevistas com gestores estaduais e o roteiro foi construído com base na Matriz de Avaliação da Regionalização da Saúde (Mars), organizada a partir dos seguintes níveis de análise: governo, gestão e assistência. Esta pesquisa foi alicerçadaâ¯naâ¯abordagemâ¯qualitativa e as categorias temáticas foram estabelecidas e fundamentadas no método analítico da análise de conteúdo. Os resultados e as discussões apontam o cenário encontrado no período pesquisado, bem como a ambiguidade da regionalização no estado; as estratégias identificadas como potentes para as regiões de saúde; e os avanços necessários para operacionalizar a regionalização. Os indicativos para o avanço da estratégia no estado estão articulados com a participação dos conselhos de saúde; a atenção básica e a conformação das redes de atenção à saúde; os instrumentos e espaços de gestão; e os recursos envolvidos. As discussões suscitadas nesta pesquisa buscam contribuir para oâ¯processo de regionalização,â¯auxiliando na análise crítica do cenário da saúde pública da Bahia.
Within the Unified Health System, regional health planning constitutes an important strategy to address the regional inequalities experienced across the territory. The state of Bahia was a pioneer in decentralizing state health administration and in having its State Department play a major role in planning regional health networks and flows. This qualitative study analyzes the process of regional health planning in Bahia, after the administrative reform which dissolved the regional directorates and created regional centers. Interviews were conducted with state managers following a script based on the Regional Health Planning Evaluation Matrix (MARS), organized from the following levels of analysis: government, management and care. Thematic categories were established and investigated using Content Analysis. The results and discussion point to an ambiguity in the state's regional planning, to important strategies for healthcare regions, and to the necessary advancements to operationalize regional planning. The latter requires the participation of health councils, primary health care, the formation of health networks, management tools and spaces and the related resources. The issues addressed here aim to contribute with the regional health planning process, collaborating with the critical analysis of the current public health scenario.
La regionalización de los servicios de salud es una importante estrategia en el Sistema Único de Salud (SUS) para hacer frente a las desigualdades regionales en salud en el territorio brasileño. El estado de Bahía fue pionero en la descentralización administrativa de los servicios de salud en el estado, además de mantener el protagonismo de la Secretaría de Estado cuanto a la planificación de redes y flujos de asistencia regional. Este artículo presenta discusiones sobre el proceso de regionalización de la salud en Bahía, después de la reforma administrativa, con extinción de las juntas regionales y con la creación regional de núcleos regionales. Se realizaron entrevistas con administradores del estado, y el guion de la entrevista se basó en la Matriz de Evaluación de Regionalización en Salud (MARS), que utiliza los siguientes niveles de análisis: gobierno, gestión y asistencia. Esta investigación tiene un enfoque cualitativo, y las categorías temáticas fueron construidas utilizando el método de análisis de contenido. Los resultados muestran el escenario encontrado en el período investigado; la ambigüedad de la regionalización en el estado; las poderosas estrategias para las regiones de salud; y los avances necesarios para poner en práctica la regionalización. Las indicaciones para el avance de la estrategia en el estado están vinculadas a la participación de los consejos de salud, la atención primaria y la formación de redes de servicios de salud, los instrumentos y espacios de gestión, y los recursos involucrados. Las discusiones resultantes de la investigación buscan contribuir al proceso de regionalización, ayudando en el análisis crítico del escenario de salud pública.
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Atención Primaria de Salud , Regionalización , Administración en Salud , Recursos en SaludRESUMEN
The cellular immune response plays an important role in COVID-19, caused by SARS-CoV-2. This feature makes use of in vitro models' useful tools to evaluate vaccines and biopharmaceutical effects. Here, we developed a two-step model to evaluate the cellular immune response after SARS-CoV-2 infection-induced or spike protein stimulation in peripheral blood mononuclear cells (PBMC) from both unexposed and COVID-19 (primo-infected) individuals (Step1). Moreover, the supernatants of these cultures were used to evaluate its effects on lung cell lines (A549) (Step2). When PBMC from the unexposed were infected by SARS-CoV-2, cytotoxic natural killer and nonclassical monocytes expressing inflammatory cytokines genes were raised. The supernatant of these cells can induce apoptosis of A549 cells (mock vs. Step2 [mean]: 6.4% × 17.7%). Meanwhile, PBMCs from primo-infected presented their memory CD4+ T cells activated with a high production of IFNG and antiviral genes. Supernatant from past COVID-19 subjects contributed to reduce apoptosis (mock vs. Step2 [ratio]: 7.2 × 1.4) and to elevate the antiviral activity (iNOS) of A549 cells (mock vs. Step2 [mean]: 31.5% × 55.7%). Our findings showed features of immune primary cells and lung cell lines response after SARS-CoV-2 or spike protein stimulation that can be used as an in vitro model to study the immunity effects after SARS-CoV-2 antigen exposure.
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COVID-19/inmunología , COVID-19/virología , Inmunidad Celular , Modelos Biológicos , SARS-CoV-2/fisiología , Adulto , Células Epiteliales Alveolares/virología , COVID-19/sangre , COVID-19/genética , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Memoria Inmunológica/inmunología , Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Fenotipo , Linfocitos T/inmunología , Replicación Viral/fisiología , Adulto JovenRESUMEN
OBJECTIVE: To estimate the prevalence and factors associated with the effect of alcohol on crack cocaine use and to analyze experiences related to combined use. Materials and methods: sequential mixed methods (qualitative and quantitative) research, carried out between August 2014 and August 2015 with people who use crack. In the quantitative approach, a cross-sectional study was conducted with 1,062 participants. Factors associated with "alcohol use with the effect of increasing the effect of crack/crack craving" were estimated by multiple regression. In the qualitative approach, 39 interviews were conducted using Bardin's content analysis technique. RESULTS: 871 (82.0%) participants reported consuming alcohol, among them, 668 (76.7%) used alcohol combined with crack: 219 (32.8%) reported feeling an effect of reduction in paranoia and/or crack craving and 384 (57.5%) reported feeling an increase in the effect of crack and in the craving to consume the drug. This relationship was also observed in the narratives of the people who use crack, with the possibility of a cyclic effect of consumption of the two substances. Those who related alcohol use to the effect of increasing crack craving (384) were more likely to use alcohol before crack (OR: 1.81; 95%CI: 1.13-2.89); to consume more than 20 stones daily (OR: 1.48; 95%CI: 1.01-2.16); to remain in abstinence from crack for less than one month (OR: 3.20; 95%CI: 1.91-5.35); to use dependence treatment services (OR: 1.85; 95%CI: 1.26-2.71); and to commit physical violence (OR:1.67; 95%CI:1.08-2.56). CONCLUSION: The findings of this study indicate that the modulation of the effect of alcohol use on crack cocaine depends on the moment when the drugs are consumed, and the use of alcohol before crack consumption is associated with characteristics that suggest a greater vulnerability to patterns of harmful crack use. Even though combined use is referred to as a way of reducing the negative effects of crack, the damage of this association may be greater than its possible benefits.