Pharmacokinetics and pharmacodynamics of dextroketamine alone or combined with midazolam in Caiman crocodilus.

Pharmacokinetics studies of anesthetic agents are important for understanding of the pharmacology and metabolism of anesthetic agents in reptilians. This study was designed to examine the pharmacokinetic and pharmacodynamic properties of intravenous dextroketamine alone or combined with midazolam in Caiman crocodilus. Eight caimans were anesthetized with dextroketamine (10 mg/kg; group D) or dextroketamine and midazolam (10 and 0.5 mg/kg respectively; group DM) into the occipital venous sinus. The pharmacokinetic parameters were calculated by HPLC using a non-compartmental modeling. Serial blood samples were collected at baseline and within 15 and 30 min, and 11.5, 2, 4, 8, 12, 24 and 48 h of drug administration. Sedation status over time differed between groups. All animals in group D (8/8; 100%) showed signs of light sedation at t10. Half (4/8; 50%) of these caimans did not progress to deeper levels of sedation. In spite of light sedation at t10, animals in group DM were deeply sedated within 13.13 ± 7.04 min of anesthetic agent injection. The area under the plasma concentration-time curve (AUC0-48) and half-life of dextroketamine changed significantly after combination with midazolam. Even without significant changes in clearance, the almost two-fold increase in the half-life of dextroketamine suggests a slower rate of elimination.

Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence.

Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to immunosenescence. Here, we evaluated the regulation of immunosenescence in lymphoid organs of senescence-accelerated prone 8 (SAM-P8) and senescence-accelerated resistant 1 (SAM-R1) mice treated with a low dose of rapamycin (RAPA). Mice were treated with a dose of 7.1 µg/kg RAPA for 2 months and had body mass and hematological parameters analyzed prior and during treatment. Cellular and humoral parameters of serum, bone marrow, thymus, and spleen samples were evaluated by ELISA, histology, and flow cytometry. Changes in body mass, hematological parameters, cell number, and in the secretion of IL-1ß, IL-6, TNF-α, IL-7, and IL-15 cytokines were different between the 2 models used. In histological analyses, we observed that SAM-P8 mice showed faster thymic involution than SAM-R1 mice. Regarding the T lymphocyte subpopulations in the spleen, CD4+ and CD8+ T cell numbers were higher and lower, respectively, in SAM-P8 mice treated with RAPA, with the opposite observed in SAM-R1. Additionally, we found that the low dose of RAPA used did not trigger changes that could compromise the immune response of these mice and the administered dose may have contributed to changes in important lymphocyte populations in the adaptive immune response and the secretion of cytokines that directly collaborate with the maturation and proliferation of these cells.

[Evaluation of the impact of the implementation of the new primary health care information system on records of patient care and home visits in Brazil]. / Avaliação do impacto da implantação do novo sistema de informações da atenção primária à saúde nos registros de atendimentos e visitas domiciliares no Brasil.

The replacement of the Primary Care Information System (SIAB, 1998-2015), as of January 2016, by the new Health Information System for Primary Care (SISAB) determined new forms of collecting, processing, and using information, with a possible impact on the records of activities carried out in primary health care in Brazil. This study aimed to evaluate the implementation impact of the new information system on records of physicians' and nurses' patient care and home visits of community health workers (CHW) in Brazil from 2007 to 2019. To this end, a Bayesian structural time-series model approach was used, based on a diffuse state-space regression. From 2016 to 2019, 463.47 million physician care, 210.61 million nursing care, and 1.28 billion CHW visits were recorded. Following the trend recorded before the implementation, 598.86 million, 430.46 million, and 1.5 billion physician and nursing appointments and CHW visits would be expected, respectively. In relative terms, there was a decrease of 25% in physician care, 51% in nursing care, and 15% in CHW visits when compared to the value expected by the Bayesian method. The negative impact on the records of patient care and home visits identified in this study, whether due to difficulties in adapting to the new system or a reduction in improper records, must be investigated so that the challenge of improving the primary care information system can be understood and overcome in a planned way.

A substituição do Sistema de Informação da Atenção Básica (SIAB, 1998-2015), a partir de janeiro de 2016, pelo novo Sistema de Informação em Saúde para a Atenção Básica (SISAB) determinou novas formas de coleta, processamento e uso das informações, com possível impacto nos registros das atividades desenvolvidas na atenção primária à saúde no Brasil. O objetivo deste estudo foi avaliar o impacto da implantação do novo sistema de informação sobre registros de atendimentos de médicos e enfermeiros, e de visitas domiciliares de agentes comunitários de saúde (ACS) brasileiros entre 2007 e 2019. Para tal, utilizou-se uma abordagem bayesiana de modelo estrutural para séries temporais, com base em uma regressão difusa de espaço-estado. Ao longo do período de 2016 a 2019, foram registrados 463,47 milhões de atendimentos médicos, 210,61 milhões de atendimentos de enfermagem e 1,28 bilhão de visitas de ACS. Seguindo a tendência registrada antes da implantação, seriam esperados 598,86 milhões, 430,46 milhões e 1,5 bilhão de atendimentos de médicos, enfermeiros e visitas de ACS, respectivamente. Em termos relativos, houve um decréscimo de 25% nos atendimentos médicos, 51% nos atendimentos de enfermagem e 15% nas visitas de ACS quando comparado com o valor esperado pelo método bayesiano. O impacto negativo no registro de atendimentos e de visitas domiciliares identificado neste estudo, seja por dificuldade de adaptação ao novo sistema, seja por diminuição de registros indevidos, merece ser alvo de investigação para que se possa, de forma planejada, compreender e superar o desafio da melhoria do sistema de informação da atenção primária.

La sustitución del Sistema de Información de la Atención Básica (SIAB, 1998-2015), desde enero de 2016, por el nuevo Sistema de Información en Salud para la Atención Básica (SISAB) estableció nuevas maneras para recolectar, procesar y utilizar las informaciones, con posibles impactos en los registros de las actividades desarrolladas en la atención primaria de salud en Brasil. El objetivo de este estudio fue evaluar el impacto de la implantación del nuevo sistema de información sobre los registros de atención de médicos y enfermeros y de visitas domiciliarias de agentes comunitarios de salud (ACS) en Brasil entre 2007 y 2019. Para eso, se utilizó un enfoque bayesiano de modelo estructural para series temporales basadas en una regresión difusa de espacio de estado. Entre los años 2016 y 2019, se registraron 463,47 millones de consultas médicas, 210,61 millones de consultas de enfermería y 1,28 mil millones de visitas de ACS. Siguiendo la tendencia registrada antes de la implantación, se esperarían 598,86 millones, 430,46 millones y 1,5 mil millones de consultas médicas y de enfermería y visitas de ACS respectivamente. En términos relativos, hubo una disminución del 25% en las consultas médicas, del 51% en las consultas de enfermería y del 15% en las visitas de ACS en comparación con el valor esperado por el método bayesiano. El impacto negativo en el registro de consultas y visitas domiciliarias identificado en este estudio, ya sea por dificultades en la adaptación al nuevo sistema o por la disminución de los registros indebidos, merece ser objeto de investigación para que se pueda, de manera planificada, comprender y superar el desafío continuo de mejorar el sistema de información de la atención primaria.

Avaliação do impacto da implantação do novo sistema de informações da atenção primária à saúde nos registros de atendimentos e visitas domiciliares no Brasil / Evaluation of the impact of the implementation of the new primary health care information system on records of patient care and home visits in Brazil / Evaluación del impacto de la implantación del nuevo sistema de informaciones de la atención primaria de salud en los registros de atención y visitas domiciliarias en Brasil

Resumo: A substituição do Sistema de Informação da Atenção Básica (SIAB, 1998-2015), a partir de janeiro de 2016, pelo novo Sistema de Informação em Saúde para a Atenção Básica (SISAB) determinou novas formas de coleta, processamento e uso das informações, com possível impacto nos registros das atividades desenvolvidas na atenção primária à saúde no Brasil. O objetivo deste estudo foi avaliar o impacto da implantação do novo sistema de informação sobre registros de atendimentos de médicos e enfermeiros, e de visitas domiciliares de agentes comunitários de saúde (ACS) brasileiros entre 2007 e 2019. Para tal, utilizou-se uma abordagem bayesiana de modelo estrutural para séries temporais, com base em uma regressão difusa de espaço-estado. Ao longo do período de 2016 a 2019, foram registrados 463,47 milhões de atendimentos médicos, 210,61 milhões de atendimentos de enfermagem e 1,28 bilhão de visitas de ACS. Seguindo a tendência registrada antes da implantação, seriam esperados 598,86 milhões, 430,46 milhões e 1,5 bilhão de atendimentos de médicos, enfermeiros e visitas de ACS, respectivamente. Em termos relativos, houve um decréscimo de 25% nos atendimentos médicos, 51% nos atendimentos de enfermagem e 15% nas visitas de ACS quando comparado com o valor esperado pelo método bayesiano. O impacto negativo no registro de atendimentos e de visitas domiciliares identificado neste estudo, seja por dificuldade de adaptação ao novo sistema, seja por diminuição de registros indevidos, merece ser alvo de investigação para que se possa, de forma planejada, compreender e superar o desafio da melhoria do sistema de informação da atenção primária.

Abstract: The replacement of the Primary Care Information System (SIAB, 1998-2015), as of January 2016, by the new Health Information System for Primary Care (SISAB) determined new forms of collecting, processing, and using information, with a possible impact on the records of activities carried out in primary health care in Brazil. This study aimed to evaluate the implementation impact of the new information system on records of physicians' and nurses' patient care and home visits of community health workers (CHW) in Brazil from 2007 to 2019. To this end, a Bayesian structural time-series model approach was used, based on a diffuse state-space regression. From 2016 to 2019, 463.47 million physician care, 210.61 million nursing care, and 1.28 billion CHW visits were recorded. Following the trend recorded before the implementation, 598.86 million, 430.46 million, and 1.5 billion physician and nursing appointments and CHW visits would be expected, respectively. In relative terms, there was a decrease of 25% in physician care, 51% in nursing care, and 15% in CHW visits when compared to the value expected by the Bayesian method. The negative impact on the records of patient care and home visits identified in this study, whether due to difficulties in adapting to the new system or a reduction in improper records, must be investigated so that the challenge of improving the primary care information system can be understood and overcome in a planned way.

Resumen: La sustitución del Sistema de Información de la Atención Básica (SIAB, 1998-2015), desde enero de 2016, por el nuevo Sistema de Información en Salud para la Atención Básica (SISAB) estableció nuevas maneras para recolectar, procesar y utilizar las informaciones, con posibles impactos en los registros de las actividades desarrolladas en la atención primaria de salud en Brasil. El objetivo de este estudio fue evaluar el impacto de la implantación del nuevo sistema de información sobre los registros de atención de médicos y enfermeros y de visitas domiciliarias de agentes comunitarios de salud (ACS) en Brasil entre 2007 y 2019. Para eso, se utilizó un enfoque bayesiano de modelo estructural para series temporales basadas en una regresión difusa de espacio de estado. Entre los años 2016 y 2019, se registraron 463,47 millones de consultas médicas, 210,61 millones de consultas de enfermería y 1,28 mil millones de visitas de ACS. Siguiendo la tendencia registrada antes de la implantación, se esperarían 598,86 millones, 430,46 millones y 1,5 mil millones de consultas médicas y de enfermería y visitas de ACS respectivamente. En términos relativos, hubo una disminución del 25% en las consultas médicas, del 51% en las consultas de enfermería y del 15% en las visitas de ACS en comparación con el valor esperado por el método bayesiano. El impacto negativo en el registro de consultas y visitas domiciliarias identificado en este estudio, ya sea por dificultades en la adaptación al nuevo sistema o por la disminución de los registros indebidos, merece ser objeto de investigación para que se pueda, de manera planificada, comprender y superar el desafío continuo de mejorar el sistema de información de la atención primaria.

Galería de imágenes de tumores malignos como herramienta didáctica en oncología / Gallery of malignancies images as didactic tool in oncology i: en

Introducción: Los tumores malignos son afecciones prevalentes que exigen un diagnóstico temprano para un tratamiento oportuno. La confección de una galería de imágenes como medio de enseñanza con la tecnología digital constituye una herramienta de aprendizaje de incuestionable valor en la especialidad de oncología. Objetivo: Confeccionar una galería de imágenes digitales de tumores malignos como medio de enseñanza alternativo para la docencia de residentes y profesionales de enfermería. Métodos: Se realizó una innovación tecnológica en el Hospital Oncológico Docente Provincial Conrado Benítez García de Santiago de Cuba, durante el bimestre enero-febrero del 2023. El objeto de estudio y el campo de acción fueron los recursos del aprendizaje y las imágenes digitalizadas sobre tumores malignos, respectivamente. Se combinaron los métodos de investigación teóricos (sistematización, vivencial y analítico sintético) y empíricos (análisis documental y encuesta en forma de cuestionario a informantes clave). Resultados: Como medio de enseñanza alternativo para la docencia médica y de enfermería, manualmente se confeccionó una galería digital con 164 imágenes de tumores malignos que incluían casi todas las localizaciones. Los expertos en informática, especialistas, residentes y enfermeras valoraron de muy adecuado el producto informático, basado en la cientificidad y la didáctica tecnológica para la formación académica integral. Conclusiones: La galería de imágenes digitales constituye una herramienta didáctica, motivacional, atractiva e interesante para el aprendizaje de las neoplasias malignas; es un recurso ilustrativo y utilitario para la docencia médica y del profesional de enfermería.

Introduction: Malignancies are prevalent affections that demand an early diagnosis for an opportune treatment. The making of an images gallery as teaching means with digital technology constitutes a learning tool of unquestionable value in the oncology specialty. Objective: To make a gallery of malignancies digital images as alternative teaching means for the residents and nursing professionals. Methods: A technological innovation was carried out in Conrado Benítez García Provincial Teaching Oncological Hospital in Santiago de Cuba, during the January-February two-month period, 2023. The study object and action field were the learning resources and the digital images on malignancies, respectively. The theoretical investigation methods (systematizing, experiential and analytic synthetic) and empiric (documental analysis and interviews in questionnaire form to key informants) were combined. Results: As alternative teaching means for medical and nursing teaching, a digital gallery was manually made with 164 malignancies images that included almost all the localizations. Computer science experts, specialists, residents and nurses valued as very appropriate the computer product, based on the scientificity and the technological didactics for the integral academic training. Conclusions: The gallery of digital images constitutes a didactic, motivational, attractive and interesting tool for learning of malignancies; it is an illustrative and utilitarian resource for medical and nursing professional teaching.

Photobiomodulation Therapy on the Palliative Care of Temporomandibular Disorder and Orofacial/Cervical Skull Pain: Preliminary Results from a Randomized Controlled Clinical Trial.

The main symptoms of temporomandibular disorders (TMDs) are pain from musculoskeletal and/or joint-in the head and neck region-and complaints of difficulty in mandibular movements. The photobiomodulation therapy (PBMT) has been reported as a promising treatment in the management of these symptoms. The objective of this research was to assess the effect of PBMT immediately after irradiation on TMDs symptoms under a prospective clinical trial, randomized, triple-blinded, placebo-controlled, and with two parallel arms. According to the RDC/TMD, maximum mouth opening (MMO) and pain in the orofacial/cervical muscles and temporomandibular joint (TMJ) were recorded. One hundred forty-five participants (71 placebo and 74 PBMT experimental) were analyzed after irradiation protocols (sham-PBMT or PBMT) at the orofacial/cervical skull musculature and at the TMJ. The results showed a reduction in the total pain score (p = 0.026), a reduction in the number of painful points (p = 0.013), and an increase in the MMO (p = 0.016) in the PBMT protocol group when compared to the placebo protocol (sham-PBMT). The PBMT was shown to be effective in reducing orofacial/cervical skull pain immediately after the irradiation. It is clinically relevant and should be taken into consideration by professionals who are dedicated to treating this pathology because, in addition to bringing comfort to patients who need dental treatment, it also consists of a low-cost and low technical complexity clinical approach.

The influence of high glucose conditions on macrophages and its effect on the autophagy pathway.

Introduction: Macrophages are central cells in mediating the inflammatory response. Objective and Methods: We evaluated the effect of high glucose conditions on the inflammatory profile and the autophagy pathway in Bone-Marrow Derived Macrophages (BMDM) from diabetic (D-BMDM) (alloxan: 60mg/kg, i.v.) and non-diabetic (ND-BMDM) C57BL/6 mice. BMDM were cultured in medium with normal glucose (5.5 mM), or high glucose (25 mM) concentration and were primed with Nigericin (20µM) stimulated with LPS (100 ng/mL) at times of 30 minutes; 2; 4; 6 and 24 hours, with the measurement of IL-6, IL-1ß and TNF-α cytokines. Results: We have further identified changes in the secretion of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α, where BMDM showed increased secretion of these cytokines after LPS + Nigericin stimulation. In addition, changes were observed in the autophagy pathway, where the increase in the autophagic protein LC3b and Beclin-1 occurred by macrophages of non-diabetic animals in hyperglycemic medium, without LPS stimulation. D-BMDM showed a reduction on the expression of LC3b and Beclin-1, suggesting an impaired autophagic process in these cells. Conclusion: The results suggest that hyperglycemia alters the inflammatory pathways in macrophages stimulated by LPS, playing an important role in the inflammatory response of diabetic individuals.

Hematoma intramiocárdico da parede inferior do ventrículo esquerdo em paciente usuário de crack / Intramyocardial hematoma of the left ventricular inferior wall in a crack user patient

Paciente masculino, 38 anos, tabagista ativo e usuário de crack com diagnóstico recente de cardiomiopatia dilatada com fração de ejeção reduzida, dá entrada no pronto socorro com queixa de dispneia classe funcional IV, edema de membros inferiores, extremidades frias, ortopneia e dispneia paroxística noturna de início há quatro dias da admissão. Afirma tratamento para tromboembolismo pulmonar e AVE isquêmico há 06 meses. Nega precordialgia ou outros sinais e sintomas. Iniciado então tratamento para insuficiência cardíaca descompensada, com necessidade de inotrópico e noradrenalina para estabilidade hemodinâmica. Realizado ecocardiograma transtorácico e evidenciada disfunção biventricular importante (FEVE = 16% e FAC = 16%), com imagem ecogênica sugestiva de hematoma intramiocárdico dissecante na parede inferior do ventrículo esquerdo, acinesia da parede anterior e hipocontratilidade das demais paredes do ventrículo esquerdo, associada a imagem sugestiva de trombo atapetando a parede anterior e estendendo-se até a região apical do ventrículo esquerdo. Realizada tomografia computadorizada do coração com realce tardio que evidenciou infarto do miocárdico de parede inferior em todas as porções e inferolateralmediobasal, sem viabilidade. Não se observou curva de biomarcadores de necrose miocárdica. Iniciado então tratamento para insuficiência cardíaca descompensada, com necessidade de inotrópico e noradrenalina para estabilidade hemodinâmica. Paciente aguardava compensação clínica e posterior discussão de abordagem cirúrgica. Realizado novo estudo ecocardiográfico transtorácico após 07 dias, com paciente em melhora clínica dos sintomas, já sem uso de inotrópicos, onde evidenciou-se: disfunção biventricular importante (FEVE = 23% e FAC = 20%), com presença de trombo preenchendo todo o interior do aneurisma dissecante da parede inferior. Uma vez da compensação clínica e alto risco de morbimortalidade com abordagem cirúrgica desses casos, optou-se por tratamento clínico com anticoagulante e medidas para insuficiência cardíaca. Após 21 de internação, paciente recebeu alta hospitalar, assintomático para seguimento ambulatorial. O aneurisma dissecante do ventrículo esquerdo é uma condição clínica rara e que está relacionada a alta morbimortalidade pelos relatos descritos na literatura médica.

O efeito do tratamento com rapamicina em órgãos linfoides de camundongos propensos à senescência acelerada / The effect of rapamycin treatment on lymphoid organs of senescence accelerated mice prone

Envelhecer compreende um fenômeno complexo, natural e irreversível, que submete o organismo a inúmeras alterações nos processos biológicos, fisiológicos, ambientais, psicológicos, comportamentais e sociais. Esse processo é caracterizado por um declínio gradual dos mecanismos homeostáticos do organismo, intimamente relacionados com o estado senescente. A senescência, quando diz respeito ao sistema imunológico, é denominada de imunossenescência, que pode ser definida como uma parada estável do ciclo celular associada a mudanças, com uma resposta que limita a proliferação de células envelhecidas ou danificadas. A autofagia está diretamente relacionada com a manutenção do fenótipo senescente, em que a atividade autofágica exerce um papel essencial e ativo na influência da biossíntese de proteínas e organelas. Essa via é regulada naturalmente pela proteína mTOR e quimicamente pelo fármaco rapamicina. Assim, pretendemos investigar: (1) as alterações no perfil corporal e hematimêtrico dos animais ao longo do tratamento com rapamicina; (2) avaliar o perfil de citocinas; (3) observar as modificações histológicas em órgãos linfoides primários e secundário; (4) analisar as populações de células linfoides e mieloides; e (5) avaliar a capacidade proliferativa de linfócitos in vitro. Camundongos SAMP-8 e SAMR-1 foram tratados com rapamicina durante dois meses. A mensuração da massa corporal e análises hematológicas foram realizadas antes e durante o tratamento. Amostras de soro, medula óssea, timo e baço foram analisados em ensaios de ELISA, histologia, população e subpopulações de células. Alterações na massa corporal, parâmetros hematológicos e celularidade de células foram nítidas entre os dois modelos utilizados. Diferenças também foram percebidas na detecção de citocinas IL-1ß. IL-6 e TNF-α, com resultados significantes nas amostras de baço, timo e medula óssea. As citocinas IL-7 e IL-15 apresentaram diferenças de secreção entre os grupos, sendo a primeira maior detectada em camundongos com senescência acelerada tratados com rapamicina. Em nossa análise histológica observamos que os camundongos SAM-P8 apresentaram involução tímica. E nas subpopulações de linfócitos T do baço, células TCD4+ e TCD8+ estavam, respectivamente, em maior e menor quantidade nos camundongos SAM-P8 tratados com rapamicina. Dessa forma, o camundongo da linhagem SAM-P8 é um excelente modelo para se estudar as alterações da senescência, em que o mesmo apresenta características fisiológicas distintas dos camundongos utilizados como controle (SAM-R1). Além disso, verificamos que a dose de rapamicina empregada não desencadeou alterações que pudessem comprometer a resposta imunológica desses camundongos, bem como na possibilidade de atuar na resposta contra os efeitos complexos do envelhecimento

Aging comprises a complex, natural, and irreversible phenomenon, which subjects the organism to countless alterations in biological, physiological, environmental, psychological, behavioral, and social processes. This process is characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to senescence effects. Senescence, when it concerns the immune system, is called immunosenescence, which can be defined as a stable cell cycle arrest associated with changes and is a response that limits the proliferation of aged or damaged cells. Autophagy is a genetically regulated, conserved cellular process and a metabolic pathway essential for maintaining cellular homeostasis, which plays a constitutive and active role in controlling the biosynthesis of proteins and organelles. This pathway is regulated naturally by mTOR or chemically by the drug rapamycin, having a direct relationship with cellular homeostasis and maintenance of the senescent phenotype. Thus, we intend to investigate: (1) the changes in the body and hematimetic profile of the animals throughout the rapamycin treatment; (2) evaluate the cytokine profile; (3) observe histological changes in primary and secondary lymphoid organs; (4) analyze lymphoid and myeloid cell populations; and (5) evaluate the proliferative capacity of lymphocytes in vitro. SAMP-8 and SAMR-1 mice were treated with rapamycin for two months. Body mass measurement and hematological analyses were performed before and during treatment. Serum, bone marrow, thymus and spleen samples were analyzed in ELISA assays, histology, cell population and subpopulations. Changes in body mass, hematological parameters, and cellularity were clear between the two models used. Differences were also noticed in the detection of cytokines IL-1ß. IL-6 and TNF-α, with significant results in the spleen, thymus and bone marrow samples. The cytokines IL-7 and IL-15 showed differences in secretion between groups, the former being higher detected in mice with accelerated senescence treated with rapamycin. In our histological analysis we observed that SAM-P8 mice showed thymic involution. And in the spleen T-lymphocyte subpopulations, TCD4+ and TCD8+ cells were, respectively, in higher and lower quantities in SAM-P8 mice treated with rapamycin. Thus, the SAM-P8 mouse is an excellent model to study the changes of senescence, since it presents physiological characteristics different from the control mice (SAM-R1). Furthermore, we verified that the dose of rapamycin used did not trigger changes that could compromise the immune response of these mice, as well as the possibility of acting in the modulatory response against the complex effects of aging

Evolução da estrutura e resultados da Atenção Primária à Saúde no Brasil entre 2008 e 2019 / Evolution of the structure and results of Primary Health Care in Brazil between 2008 and 2019

Resumo Descreve a evolução da estrutura e resultados da Atenção Primária à Saúde (APS) no Brasil, entre 2008 e 2019. Foram calculadas a mediana de variáveis como: despesa per capita em APS por habitante coberto, cobertura da APS e as taxas de mortalidade e internações por condições sensíveis à atenção primária (CSAP) de 5.565 municípios brasileiros estratificados segundo porte populacional e quintil do Índice Brasileiro de Privação (IBP) e analisada a tendência mediana no período. Houve aumento de 12% na mediana da despesa em APS. A cobertura da APS expandiu, sendo que 3.168 municípios apresentaram 100% de cobertura em 2019, contra 2.632 em 2008. A mediana das taxas de mortalidade e internações por CSAP aumentou 0,2% e diminuiu 44,9% respectivamente. A despesa em APS foi menor nos municípios com maior privação socioeconômica. Quanto maior o porte populacional e melhores as condições socioeconômicas dos municípios, menor a cobertura da APS. Quanto maior a privação socioeconômica dos municípios, maiores foram as medianas das taxas de mortalidade por CSAP. Este estudo demonstrou que a evolução da APS foi heterogênea e está associada tanto ao porte populacional como às condições socioeconômicas dos municípios.

Abstract This paper describes the structure and results of Primary Health Care (PHC) in Brazil between 2008 and 2019. The medians of the following variables were calculated: PHC spending per inhabitant covered, PHC coverage, and rates of mortality and hospitalizations due to primary care sensitive conditions (PCSC), in 5,565 Brazilian municipalities stratified according to population size and quintile of the Brazilian Deprivation Index (IBP), and the median trend in the period was analyzed. There was a 12% increase in median PHC spending. PHC coverage expanded, with 3,168 municipalities presenting 100% coverage in 2019, compared to 2,632 in 2008. The median rates of PCSC mortality and hospitalizations increased 0.2% and decreased 44.9%, respectively. PHC spending was lower in municipalities with greater socioeconomic deprivation. The bigger the population and the better the socioeconomic conditions were in the municipalities, the lower the PHC coverage. The greater the socioeconomic deprivation was in the municipalities, the higher the median PCSC mortality rates. This study showed that the evolution of PHC was heterogeneous and is associated both with the population size and with the socioeconomic conditions of the municipalities.

Evolution of the structure and results of Primary Health Care in Brazil between 2008 and 2019. / Evolução da estrutura e resultados da Atenção Primária à Saúde no Brasil entre 2008 e 2019.

This paper describes the structure and results of Primary Health Care (PHC) in Brazil between 2008 and 2019. The medians of the following variables were calculated: PHC spending per inhabitant covered, PHC coverage, and rates of mortality and hospitalizations due to primary care sensitive conditions (PCSC), in 5,565 Brazilian municipalities stratified according to population size and quintile of the Brazilian Deprivation Index (IBP), and the median trend in the period was analyzed. There was a 12% increase in median PHC spending. PHC coverage expanded, with 3,168 municipalities presenting 100% coverage in 2019, compared to 2,632 in 2008. The median rates of PCSC mortality and hospitalizations increased 0.2% and decreased 44.9%, respectively. PHC spending was lower in municipalities with greater socioeconomic deprivation. The bigger the population and the better the socioeconomic conditions were in the municipalities, the lower the PHC coverage. The greater the socioeconomic deprivation was in the municipalities, the higher the median PCSC mortality rates. This study showed that the evolution of PHC was heterogeneous and is associated both with the population size and with the socioeconomic conditions of the municipalities.

Descreve a evolução da estrutura e resultados da Atenção Primária à Saúde (APS) no Brasil, entre 2008 e 2019. Foram calculadas a mediana de variáveis como: despesa per capita em APS por habitante coberto, cobertura da APS e as taxas de mortalidade e internações por condições sensíveis à atenção primária (CSAP) de 5.565 municípios brasileiros estratificados segundo porte populacional e quintil do Índice Brasileiro de Privação (IBP) e analisada a tendência mediana no período. Houve aumento de 12% na mediana da despesa em APS. A cobertura da APS expandiu, sendo que 3.168 municípios apresentaram 100% de cobertura em 2019, contra 2.632 em 2008. A mediana das taxas de mortalidade e internações por CSAP aumentou 0,2% e diminuiu 44,9% respectivamente. A despesa em APS foi menor nos municípios com maior privação socioeconômica. Quanto maior o porte populacional e melhores as condições socioeconômicas dos municípios, menor a cobertura da APS. Quanto maior a privação socioeconômica dos municípios, maiores foram as medianas das taxas de mortalidade por CSAP. Este estudo demonstrou que a evolução da APS foi heterogênea e está associada tanto ao porte populacional como às condições socioeconômicas dos municípios.

A new species of Conognatha (Pithiscus) from Minas Gerais State in Brazil (Coleoptera: Buprestidae).

Conognatha (Pithiscus) continua Pineda, Koike Barros sp. nov. (Coleoptera: Buprestidae: Stigmoderini), from southeast Brazil is described and illustrated. A simplified identification key for the Conognatha (P.) continua species-group is proposed.

Bovine pancreatic trypsin inhibitor and soybean Kunitz trypsin inhibitor: Differential effects on proteases and larval development of the soybean pest Anticarsia gemmatalis (Lepidoptera: Noctuidae).

Pest management is challenged with resistant herbivores and problems regarding human health and environmental issues. Indeed, the greatest challenge to modern agriculture is to protect crops from pests and still maintain environmental quality. This study aimed to analyze by in silico, in vitro, and in vivo approaches to the feasibility of using the inhibitory protein extracted from mammals - Bovine Pancreatic Trypsin Inhibitor (BPTI) as a potential inhibitor of digestive trypsins from the pest Anticarsia gemmatalis and comparing the results with the host-plant inhibitor - Soybean Kunitz Trypsin Inhibitor (SKTI). BPTI and SKTI interacts with A. gemmatalis trypsin-like enzyme competitively, through hydrogen and hydrophobic bonds. A. gemmatalis larvae exposed to BPTI did not show two common adaptative mechanisms i.e., proteolytic degradation and overproduction of proteases, presenting highly reduced trypsin-like activity. On the other hand, SKTI-fed larvae did not show reduced trypsin-like activity, presenting overproduction of proteases and SKTI digestion. In addition, the larval survival was reduced by BPTI similarly to SKTI, and additionally caused a decrease in pupal weight. The non-plant protease inhibitor BPTI presents intriguing element to compose biopesticide formulations to help decrease the use of conventional refractory pesticides into integrated pest management programs.

Financing of health and the fiscal dependency of Brazilian municipalities between 2004 and 2019. / Financiamento da saúde e dependência fiscal dos municípios brasileiros entre 2004 e 2019.

This article describes the evolution of municipal financing of the Unified Health System, from 2004 to 2019, considering revenues and expenses from own and non-own sources, analyzes fiscal redistribution, according to population size and average household income, and compares this evolution in two periods, characterized as economic growth (2004-2014) and recession (2015-2019). The study was based on data from the Information System on Public Health Budgets. There was real growth in municipal spending on health from 2004 to 2014 (156.3%), with a drop between 2014 and 2015, followed by a recovery between 2015 and 2019. During the recession period, there was an overall increase in the fiscal dependence of municipalities, indicated by the increase in non-own revenues, even with the decrease in the Federal Government participation in transfers. The growth of own health expenses was lower among municipalities with lower household income, while for non-own expenses it was higher in municipalities with a smaller population size. In short, the results indicate a process of increasing municipal spending on health, as well as the increased fiscal dependence of municipalities to fund health, intensified after the 2015 crisis, which especially affected small and lower income municipalities.

Este artigo descreve a evolução do financiamento municipal do Sistema Único de Saúde, de 2004 a 2019, considerando receitas e despesas de fontes próprias e não-próprias, analisa a redistribuição fiscal, de acordo com o porte populacional e a renda média domiciliar, e compara essa evolução em dois períodos, caracterizados como de crescimento econômico (2004-2014) e de recessão (2015-2019). O estudo se baseou em dados do Sistema de Informações sobre Orçamentos Públicos em Saúde. Constatou-se crescimento real dos gastos municipais em saúde de 2004 a 2014 (156,3%), com queda entre 2014 e 2015, seguida de recuperação até 2019. Na recessão, detectou-se aumento global da dependência fiscal dos municípios, indicada pelo aumento de receitas não-próprias, mesmo com a diminuição da participação da União nas transferências. O crescimento das despesas próprias em saúde foi menor entre os municípios de menor renda domiciliar, enquanto para as despesas não-próprias foi maior nos municípios de menor porte populacional. Em suma, indica-se um processo de incremento dos gastos municipais em saúde, assim como o aumento da dependência fiscal para custeio da saúde, intensificado após a crise de 2015, que atingiu especialmente os municípios de pequeno porte e de menor renda domiciliar.

Arginine-containing dipeptides decrease affinity of gut trypsins and compromise soybean pest development.

The design and production of molecules capable of mimicking the binding or/and functional sites of proteins inhibitors represent a promising strategy for the exploration and modulation of gut trypsin function in insect pests, specifically Lepidoptera. Here, for the first time, we characterized the trypsin activity present in the gut, performance and development of Anticarsia gemmatalis (Lepidoptera: Noctuidae) larvae when exposed to arginine-containing dipeptides. In silico assessment showed that arginine-containing dipeptides have a greater affinity for the active site of A. gemmatalis trypsins than lysine-containing peptides due to the presence of the double-charged guanidinium group that enhances the interaction at the S1 subsite of trypsins. Furthermore, the inhibitory and anti-insect potential of the peptides was demonstrated through kinetic and larval life cycle parameters, respectively. These dipeptides showed structural stability, binding to the active site, corroborated in vitro (competitive inhibition), and significant reduction of trypsin enzyme activity in the gut, survival, and weight of the A. gemmatalis larvae. Our findings reinforce the idea that small peptides are promising candidates for lepidopteran pest management. The optimization of DI2 and DI1 peptides, enhancing uptake and affinity to trypsins, may turn the use of these molecules feasible in agriculture.

Financiamento da saúde e dependência fiscal dos municípios brasileiros entre 2004 e 2019 / Financing of health and the fiscal dependency of Brazilian municipalities between 2004 and 2019

Resumo Este artigo descreve a evolução do financiamento municipal do Sistema Único de Saúde, de 2004 a 2019, considerando receitas e despesas de fontes próprias e não-próprias, analisa a redistribuição fiscal, de acordo com o porte populacional e a renda média domiciliar, e compara essa evolução em dois períodos, caracterizados como de crescimento econômico (2004-2014) e de recessão (2015-2019). O estudo se baseou em dados do Sistema de Informações sobre Orçamentos Públicos em Saúde. Constatou-se crescimento real dos gastos municipais em saúde de 2004 a 2014 (156,3%), com queda entre 2014 e 2015, seguida de recuperação até 2019. Na recessão, detectou-se aumento global da dependência fiscal dos municípios, indicada pelo aumento de receitas não-próprias, mesmo com a diminuição da participação da União nas transferências. O crescimento das despesas próprias em saúde foi menor entre os municípios de menor renda domiciliar, enquanto para as despesas não-próprias foi maior nos municípios de menor porte populacional. Em suma, indica-se um processo de incremento dos gastos municipais em saúde, assim como o aumento da dependência fiscal para custeio da saúde, intensificado após a crise de 2015, que atingiu especialmente os municípios de pequeno porte e de menor renda domiciliar.

Abstract This article describes the evolution of municipal financing of the Unified Health System, from 2004 to 2019, considering revenues and expenses from own and non-own sources, analyzes fiscal redistribution, according to population size and average household income, and compares this evolution in two periods, characterized as economic growth (2004-2014) and recession (2015-2019). The study was based on data from the Information System on Public Health Budgets. There was real growth in municipal spending on health from 2004 to 2014 (156.3%), with a drop between 2014 and 2015, followed by a recovery between 2015 and 2019. During the recession period, there was an overall increase in the fiscal dependence of municipalities, indicated by the increase in non-own revenues, even with the decrease in the Federal Government participation in transfers. The growth of own health expenses was lower among municipalities with lower household income, while for non-own expenses it was higher in municipalities with a smaller population size. In short, the results indicate a process of increasing municipal spending on health, as well as the increased fiscal dependence of municipalities to fund health, intensified after the 2015 crisis, which especially affected small and lower income municipalities.

What is the impact of dynamic contrast-enhancement sequence in the Vesical Imaging, Reporting and Data System (VI-RADS)? A subgroup analysis.

BACKGROUND: A scoring system focusing on the risk of muscle layer invasion by Bladder cancer (BCa) has been released, Vesical Imaging - Radiological and Data System (VI-RADS), with a growing interest in evaluating its diagnostic accuracy. Our goal was to assess the accuracy and reproducibility of the VI-RADS score for assessment of the vesical muscular layer with (multiparametric-mp) and without (biparametric-bp) a dynamic-contrast enhancement (DCE) sequence. METHODS: Retrospective study conducted from July 2018 to July 2020. All patients had suspicions of BCa and underwent Magnetic Resonance Imaging (MRI) before any intervention. MRI was interpreted by two radiologists with different levels of experience, and a VI-RADS score assigned in two different sessions (3 months apart) without and with DCE. After exclusions, 44 patients with 50 lesions were enrolled. The standard of reference was transurethral resection in 18 patients (40.9%) and cystectomy in 26 patients (59.1%). RESULTS: Twenty-five lesions (50%) were muscle-invasive. There was no significant difference between the two groups for gender and presence of a stalk, but mean age of NMIBCa group was significantly higher (p = 0.01). The sizes of lesions were significantly different between groups for both readers at 2.42+/- 1.58 vs. 5.70+/- 2.67 cm for reader 1 (p < 0.0001) and 2.37+/- 1.50 vs. 5.44 +/- 2.90 cm for reader 2 (p = 0.001). The area under the curve (AUC) for muscle invasion with mpVI-RADS, considering all lesions, was 0.885 +/- 0.04 (95% CI-0.79-0.98) for reader 1 and 0.924 +/- 0.04 (0.84-0.99) for reader 2, and for bpVI-RADS was 0.879+/- 0.05 and 0.916 +/- 0.04 (0.85-0.99), respectively, both differences not statistically significant (p = 0.24 and 0.07, respectively). When considering only small lesions (< 3.0 cm), the accuracy for mpVI-RADS was 0.795 +/- 0.11 (0.57-1.0) for reader1, and 0.80 +/- 0.11(0.57-1.0) for reader 2, a non-significant difference (p = 0.56) and for bpVI-RADS was 0.747 +/- 0.12 (0.50-0.99) for reader 1 and 0.80 +/- 0.11(0.57-1.0) for reader 2, a significant difference (p = 0.04). The intraclass correlation coefficient for the final score was 0.81 (0.60-1.0) for mpVI-RADS and 0.85 (0.63-1.0) for bpVI-RADS. CONCLUSION: The VI-RADS system was accurate in demonstrating muscle-invasive BCa, for both experienced and less experienced reader, regardless of the use of a DCE sequence. However, when only small lesions were assessed the difference between the two readers was significant only for the biparametric analysis. The reproducibility was similar between multiparametric and biparametric approach.

Overhydration in acute kidney injury: Is it always a menace to critically ill patients? A survival study using bioimpedance spectroscopy.

INTRODUCTION: The hydration status is a predictor of survival in critically ill patients. However, it is unclear whether this association depends on the patient clinical condition. This study was designed to analyze the impact of hydration status on survival of critically ill patients with acute kidney injury (AKI) with or without sepsis. METHODS: A prospective cohort study following critically ill patients with AKI consecutively admitted over a one-year period to a teaching hospital intensive care unit (ICU). All patients with AKI stage three or higher of the KDIGO score were included. The hydration status was evaluated through the overhydration (OH) parameter of spectroscopy bioimpedance and sepsis was defined according Sepse-3 criteria. The survival analysis used adjusted competing-risks regression. RESULTS: Forty-eight patients were included, 27 (56%) with a sepsis diagnosis. The main negative predictors of survival among sepsis patients, adjusted by SAPS3 score, were higher OH (SHR 1.1, 95% CI 1.0-1.2, p = 0.02), mechanical ventilation (SHR 6.9, 95% CI 1.0-47.8, p = 0.04) and older age (SHR 1.1, 95% CI 1.0-1.1, p = 0.005). The predictors in non-sepsis patients were lower OH (SHR 0.82, 95% CI 0.71-0.95, p = 0.008) and mechanical ventilation (SHR 12, 95% CI 2.4-6.6, p < 0.001). CONCLUSIONS: This finding suggests that extracellular overhydration is an independent predictor of survival in critically ill patients with sepsis, but it seems to have opposite effect in non-sepsis patients.

Ageing is associated with maladaptive immune response and worse outcome after traumatic brain injury.

Traumatic brain injury is increasingly common in older individuals. Older age is one of the strongest predictors for poor prognosis after brain trauma, a phenomenon driven by the presence of extra-cranial comorbidities as well as pre-existent pathologies associated with cognitive impairment and brain volume loss (such as cerebrovascular disease or age-related neurodegeneration). Furthermore, ageing is associated with a dysregulated immune response, which includes attenuated responses to infection and vaccination, and a failure to resolve inflammation leading to chronic inflammatory states. In traumatic brain injury, where the immune response is imperative for the clearance of cellular debris and survey of the injured milieu, an appropriate self-limiting response is vital to promote recovery. Currently, our understanding of age-related factors that contribute to the outcome is limited; but a more complete understanding is essential for the development of tailored therapeutic strategies to mitigate the consequences of traumatic brain injury. Here we show greater functional deficits, white matter abnormalities and worse long-term outcomes in aged compared with young C57BL/6J mice after either moderate or severe traumatic brain injury. These effects are associated with altered systemic, meningeal and brain tissue immune response. Importantly, the impaired acute systemic immune response in the mice was similar to the findings observed in our clinical cohort. Traumatic brain-injured patient cohort over 70 years of age showed lower monocyte and lymphocyte counts compared with those under 45 years. In mice, traumatic brain injury was associated with alterations in peripheral immune subsets, which differed in aged compared with adult mice. There was a significant increase in transcription of immune and inflammatory genes in the meninges post-traumatic brain injury, including monocyte/leucocyte-recruiting chemokines. Immune cells were recruited to the region of the dural injury, with a significantly higher number of CD11b+ myeloid cells in aged compared with the adult mice. In brain tissue, when compared with the young adult mice, we observed a more pronounced and widespread reactive astrogliosis 1 month after trauma in aged mice, sustained by an early and persistent induction of proinflammatory astrocytic state. These findings provide important insights regarding age-related exacerbation of neurological damage after brain trauma.