Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis.

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1-/- mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD.

First Cases of Feline Sporotrichosis Caused by Sporothrix brasiliensis in Paraguay.

Sporothrix brasiliensis is an emerging fungal pathogen causing cat-transmitted sporotrichosis, an epi-zoonosis affecting humans, cats and dogs in Brazil and now spreading to neighboring South American countries. Here, we report the first two autochthonous cases of cat-transmitted sporotrichosis in Paraguay. The first case was a four-year-old male cat showing several ulcerative lesions, nasal deformity and respiratory symptoms. The second case was a one-year-old male cat showing a single ulcerated lesion, respiratory symptoms and nasal deformity. Both cases were admitted to a veterinary clinic in Ciudad del Este, Paraguay. Isolates were recovered from swabs of the two cases. Using molecular methods, the isolates were identified as S. brasiliensis.

GPR43 stimulation on TCRαß+ intraepithelial colonic lymphocytes inhibits the recruitment of encephalitogenic T-cells into the central nervous system and attenuates the development of autoimmunity.

INTRODUCTION: Gut microbiota plays a critical role in the regulation of immune homeostasis. Accordingly, several autoimmune disorders have been associated with dysbiosis in the gut microbiota. Notably, the dysbiosis associated with central nervous system (CNS) autoimmunity involves a substantial reduction of bacteria belonging to Clostridia clusters IV and XIVa, which constitute major producers of short-chain fatty acids (SCFAs). Here we addressed the role of the surface receptor-mediated effects of SCFAs on mucosal T-cells in the development of CNS autoimmunity. METHODS: To induce CNS autoimmunity, we used the mouse model of experimental autoimmune encephalomyelitis (EAE) induced by immunization with the myelin oligodendrocyte glycoprotein (MOG)-derived peptide (MOG35-55 peptide). To address the effects of GPR43 stimulation on colonic TCRαß+ T-cells upon CNS autoimmunity, mucosal lymphocytes were isolated and stimulated with a selective GPR43 agonist ex vivo and then transferred into congenic mice undergoing EAE. Several subsets of lymphocytes infiltrating the CNS or those present in the gut epithelium and gut lamina propria were analysed by flow cytometry. In vitro migration assays were conducted with mucosal T-cells using transwells. RESULTS: Our results show a sharp and selective reduction of intestinal propionate at the peak of EAE development, accompanied by increased IFN-γ and decreased IL-22 in the colonic mucosa. Further analyses indicated that GPR43 was the primary SCFAs receptor expressed on T-cells, which was downregulated on colonic TCRαß+ T-cells upon CNS autoimmunity. The pharmacologic stimulation of GPR43 increased the anti-inflammatory function and reduced the pro-inflammatory features in several TCRαß+ T-cell subsets in the colonic mucosa upon EAE development. Furthermore, GPR43 stimulation induced the arrest of CNS-autoreactive T-cells in the colonic lamina propria, thus avoiding their infiltration into the CNS and dampening the disease development. Mechanistic analyses revealed that GPR43-stimulation on mucosal TCRαß+ T-cells inhibits their CXCR3-mediated migration towards CXCL11, which is released from the CNS upon neuroinflammation. CONCLUSIONS: These findings provide a novel mechanism involved in the gut-brain axis by which bacterial-derived products secreted in the gut mucosa might control the CNS tropism of autoreactive T-cells. Moreover, this study shows GPR43 expressed on T-cells as a promising therapeutic target for CNS autoimmunity.

¿Cuáles son las brechas de conocimiento y qué priorizar en investigación en salud mental del adulto mayor? Estudio cuali-cuantitativo utilizando la matriz de estrategias combinadas para Argentina (MECA).

INTRODUCCIÓN: el envejecimiento poblacional es un fenómeno mundial. Los problemas de salud mental, altamente prevalentes en este grupo, impactan en la vida de los individuos, sus familias y la sociedad en su conjunto. OBJETIVO: identificar brechas de conocimiento y prioridades de investigación en salud mental del adulto mayor en Argentina. MATERIAL Y MÉTODOS: diseño cuali-cuantitativo, en tres etapas: (1) diagnóstico de situación, (2) evaluación global de necesidades de investigación y (3) ejercicio de priorización basado en la Matriz de Estrategias Combinadas validada para Argentina (MECA). RESULTADOS: con base en las primeras dos etapas del estudio se identificaron dos áreas temáticas investigar en el país y dimensiones priorizadas: (a) soledad-aislamiento y (b) deterioro cognitivo y demencia. Como resultado del ejercicio de priorización surgieron las siguientes dimensiones: en relación con soledad-aislamiento: 1. efecto de los programas, 2. falta de acceso a los recursos, 3. capacidad de adaptación a los contextos locales (integración social del adulto mayor) y 4. calidad de servicios. En relación con deterioro cognitivo y demencia: 1. impacto cuidadores y entorno, 2. barreras para la implementación de guías y capacitación, 3. estudios de costo-efectividad sobre intervenciones y calidad de vida, y 4. recolección y publicación de datos epidemiológicos. CONCLUSIÓN: se debe enfatizar la importancia de fortalecer la investigación en Argentina sobre la implementación y difusión de intervenciones de promoción, prevención y prestación de servicios en la salud mental del adulto mayor.

Dopaminergic Signalling Enhances IL-2 Production and Strengthens Anti-Tumour Response Exerted by Cytotoxic T Lymphocytes in a Melanoma Mouse Model.

Dopamine has emerged as an important regulator of immunity. Recent evidence has shown that signalling through low-affinity dopamine receptors exerts anti-inflammatory effects, whilst stimulation of high-affinity dopamine receptors potentiates immunity in different models. However, the dopaminergic regulation of CD8+ T-cells in anti-tumour immunity remains poorly explored. Here, we studied the role of dopamine receptor D3 (DRD3), which displays the highest affinity for dopamine, in the function of CD8+ T-cells and its consequences in the anti-tumour immune response. We observed that the deficiency of Drd3 (the gene encoding DRD3) in CD8+ T-cells limits their in vivo expansion, leading to an impaired anti-tumour response in a mouse melanoma model. Mechanistic analyses suggest that DRD3 stimulation favours the production of interleukin 2 (IL-2) and the surface expression of CD25, the α-chain IL-2 receptor, which are required for expansion and effector differentiation of CD8+ T-cells. Thus, our results provide genetic and pharmacologic evidence indicating that DRD3 favours the production of IL-2 by CD8+ T-cells, which is associated with higher expansion and acquisition of effector function of these cells, promoting a more potent anti-tumour response in a melanoma mouse model. These findings contribute to understanding how dopaminergic signalling affects the cellular immune response and represent an opportunity to improve melanoma therapy.

[Implementation of the HEARTS Initiative in Argentina: initial resultsImplementação da Iniciativa HEARTS na Argentina: primeiros resultados]. / Implementación de la Iniciativa HEARTS en Argentina: primeros resultados.

Cardiovascular diseases are the leading cause of mortality and morbidity in the Region of the Americas, and hypertension is one of the main risk factors. In 2018, Argentina began implementing the HEARTS Initiative in five primary health care centers, through the National Plan for the Prevention and Control of Arterial Hypertension. This study presents the impact its implementation has had on the indicators of effective coverage, treatment, combination therapy, and control. The HEARTS Initiative has multiple components; these include training health teams, reassigning tasks based on the transfer of clinical competencies, providing automatic and clinically validated blood pressure measurement devices, and using a single standardized treatment protocol. A longitudinal data model (generalized estimating equation analysis) was used, and the information from the five health centers was grouped using weighted averages according to the size of the population under coverage. Analysis of the results was stratified into two time periods delimited by the imposition of restrictions due to COVID-19. During the first period of 18 months, significant improvement was observed in treatment (5.9%; p<0.01) and combination therapy (13.4%; p<0.01), with no significant change in coverage (8.4%; p=0.87) and with a paradoxical decrease in control (-3.3%; p=0.02). When the period of restrictions was compared to the previous period, a generalized reduction was observed in all indicators, particularly coverage (-23.6%; p<0.01) and control (-12.5%; p<0.01). However, treatment and combination therapy levels remained above baseline values (1.7%; p<0.01 and 5.4%; p<0.01, respectively).

As doenças cardiovasculares são a principal causa de morbimortalidade, e a hipertensão, seu principal fator de risco. Em 2018, a Argentina começou a implementar a Iniciativa HEARTS em 5 centros de atenção primária à saúde por meio do Plano Nacional de Prevenção e Controle da Hipertensão Arterial. Este estudo apresenta o impacto de sua implementação nos indicadores de cobertura efetiva, tratamento, tratamento combinado e controle. A Iniciativa HEARTS inclui vários componentes. Entre eles, se destacam a capacitação das equipes de saúde, a reorganização das tarefas com base na transferência de competências clínicas, a disponibilização de aparelhos automáticos e clinicamente validados para aferição da pressão arterial e a utilização de um único protocolo padronizado de tratamento. Foi utilizado um modelo de equações de estimativas generalizadas para a análise de dados longitudinais, e as informações dos 5 centros de saúde foram agrupadas por meio de médias ponderadas de acordo com o tamanho da população coberta. A análise dos resultados foi estratificada em dois períodos de tempo delimitados pela irrupção das restrições em virtude da COVID-19. Durante os primeiros 18 meses, houve melhora significativa no tratamento (5,9%; p<0,01) e no tratamento combinado (13,4%; p<0,01), sem mudança significativa na cobertura (8,4%; p=0,87) e com uma diminuição paradoxal no controle (−3,3%; p=0,02). Durante as restrições e em relação ao período anterior, verificou-se redução generalizada em todos os indicadores, principalmente na cobertura (−23,6%; p<0,01) e no controle (−12,5%; p<0,01). No entanto, os níveis de tratamento e tratamento combinado persistiram acima dos valores basais (1,7%; p<0,01 e 5,4%; p<0,01, respectivamente).

Implementación de la Iniciativa HEARTS en Argentina: primeros resultados

[RESUMEN]. Las enfermedades cardiovasculares son la principal causa de morbimortalidad, y la hipertensión es su principal factor de riesgo. En 2018, Argentina comenzó a implementar la Iniciativa HEARTS en 5 centros de atención primaria de salud a través del Plan Nacional de Prevención y Control de la Hipertensión Arterial. En este estudio se presenta el impacto de su implementación en los indicadores de cobertura efectiva, tratamiento, tratamiento combinado y control. La Iniciativa HEARTS incluye múltiples componentes; entre ellos se destacan la capacitación de los equipos de salud, la reorganización de las tareas basada en la transferencia de competencias clínicas, la provisión de dispositivos de medición de la presión arterial automáticos y clínicamente validados, y la utilización de un único protocolo de tratamiento estandarizado. Se utilizó un modelo de datos longitudinales del tipo ecuación de estimación generalizada, y se agrupó la información de los 5 centros de salud mediante promedios ponderados según el tamaño de la población bajo cobertura. El análisis de los resultados fue estratificado en dos períodos de tiempo delimitados por la irrupción de las restricciones debidas al COVID-19. Durante el primer período de 18 meses se observó una mejoría significativa en el tratamiento (5,9%; p<0,01) y el tratamiento combinado (13,4%; p<0,01), sin cambios significativos en la cobertura (8,4%; p=0,87) y con un descenso paradojal en el control (−3,3%; p=0,02). Durante las restricciones y respecto del período previo, se constató una reducción generalizada en todos los indicadores, principalmente en la cobertura (−23,6%; p<0,01) y el control (−12,5%; p<0,01). Sin embargo, los niveles de tratamiento y tratamiento combinado persistieron por encima de los valores basales (1,7%; p<0,01 y 5,4%; p<0,01, respectivamente).

[ABSTRACT]. Cardiovascular diseases are the leading cause of mortality and morbidity in the Region of the Americas, and hypertension is one of the main risk factors. In 2018, Argentina began implementing the HEARTS Initiative in five primary health care centers, through the National Plan for the Prevention and Control of Arterial Hypertension. This study presents the impact its implementation has had on the indicators of effective coverage, treatment, combination therapy, and control. The HEARTS Initiative has multiple components; these include training health teams, reassigning tasks based on the transfer of clinical competencies, providing automatic and clinically validated blood pressure measurement devices, and using a single standardized treatment protocol. A longitudinal data model (generalized estimating equation analysis) was used, and the information from the five health centers was grouped using weighted averages according to the size of the population under coverage. Analysis of the results was stratified into two time periods delimited by the imposition of restrictions due to COVID-19. During the first period of 18 months, significant improvement was observed in treatment (5.9%; p<0.01) and combination therapy (13.4%; p<0.01), with no significant change in coverage (8.4%; p=0.87) and with a paradoxical decrease in control (−3.3%; p=0.02). When the period of restrictions was compared to the previous period, a generalized reduction was observed in all indicators, particularly coverage (−23.6%; p<0.01) and control (−12.5%; p<0.01). However, treatment and combination therapy levels remained above baseline values (1.7%; p<0.01 and 5.4%; p<0.01, respectively).

[RESUMO]. As doenças cardiovasculares são a principal causa de morbimortalidade, e a hipertensão, seu principal fator de risco. Em 2018, a Argentina começou a implementar a Iniciativa HEARTS em 5 centros de atenção primária à saúde por meio do Plano Nacional de Prevenção e Controle da Hipertensão Arterial. Este estudo apresenta o impacto de sua implementação nos indicadores de cobertura efetiva, tratamento, tratamento combinado e controle. A Iniciativa HEARTS inclui vários componentes. Entre eles, se destacam a capacitação das equipes de saúde, a reorganização das tarefas com base na transferência de competências clínicas, a disponibilização de aparelhos automáticos e clinicamente validados para aferição da pressão arterial e a utilização de um único protocolo padronizado de tratamento. Foi utilizado um modelo de equações de estimativas generalizadas para a análise de dados longitudinais, e as informações dos 5 centros de saúde foram agrupadas por meio de médias ponderadas de acordo com o tamanho da população coberta. A análise dos resultados foi estratificada em dois períodos de tempo delimitados pela irrupção das restrições em virtude da COVID-19. Durante os primeiros 18 meses, houve melhora significativa no tratamento (5,9%; p<0,01) e no tratamento combinado (13,4%; p<0,01), sem mudança significativa na cobertura (8,4%; p=0,87) e com uma diminuição paradoxal no controle (−3,3%; p=0,02). Durante as restrições e em relação ao período anterior, verificou-se redução generalizada em todos os indicadores, principalmente na cobertura (−23,6%; p<0,01) e no controle (−12,5%; p<0,01). No entanto, os níveis de tratamento e tratamento combinado persistiram acima dos valores basais (1,7%; p<0,01 e 5,4%; p<0,01, respectivamente).

Tasa de filtración glomerular conservada en personas mayores. Un estudio de base poblacional en el Cono Sur de América Latina

Introduction: Kidneys are affected by the aging process, usually suffering a progressive glomerular filtration rate (GFR) reduction of around 1 ml/year as of 30 years of age. Nevertheless, few older subjects show a stable GFR over time. This phenomenon has not been exhaustively studied, and even less in the Southern Cone. Aim: The aim was to estimate the prevalence of preserved GFR in a representative sample of older adults and explore the association between cardiovascular risk factors and preserved GFR in older individuals. Methods: We used data from a cross-sectional survey of a random sample of 1571 participants aged 65-74 years from 4 cities of the Southern Cone. We describe the prevalence of eGFR ≥80 ml/min/1.73 m2 and sociodemographic, biological, behavioral risk factors and medication use. Backward stepwise logistic regression analysis was used to study the effect of cardiovascular risk factors on eGFR ≥80 ml/min. Results: In this study, 962 had an eGFR >80 ml/min/1.73 m2 and 154 were healthy adults (Prevalence= 17.01% (95%CI 14.5%; 19.9%)). The median eGFR in the full sample was 85.53 ml/min/1.73 m² (IQR: 73.12-91.26). The prevalence of eGFR >80 ml/min/1.73 m2 was higher among men. Overall, older adults with no cardiovascular risk factors and eGFR >80 ml/min/1.73 m2 were predominantly men and showed a lower prevalence of dyslipidemia. Conclusion: The present study documented that 17% of healthy older individuals have preserved glomerular filtration rate (eGFR>80 ml/min/1.73 m2) despite their advanced age.

Introducción: Los riñones se ven afectados por el proceso de envejecimiento, sufriendo habitualmente una reducción progresiva de la tasa de filtración glomerular (TFG) de alrededor de 1 ml/año a partir de los 30 años de edad. Sin embargo, son pocos los sujetos de edad avanzada que muestran una TFG estable a lo largo del tiempo. Este fenómeno no ha sido estudiado exhaustivamente, y menos aún en el Cono Sur. Objetivo: El objetivo fue estimar la prevalencia de la TFG conservada en una muestra representativa de adultos mayores y explorar la asociación entre los factores de riesgo cardiovascular y la TFG conservada en individuos de edad avanzada. Métodos: Utilizamos datos de una encuesta transversal de una muestra aleatoria de 1571 participantes de 65-74 años de edad de 4 ciudades del Cono Sur. Describimos la prevalencia de FGe ≥80 ml/min/1,73 m2 y los factores de riesgo sociodemográficos, biológicos y conductuales y el uso de medicamentos. Se utilizó un análisis de regresión logística por pasos hacia atrás para estudiar el efecto de los factores de riesgo cardiovascular sobre la TFGe ≥80 ml/min. Resultados: En este estudio, 962 tenían una TFGe >80 ml/min/1,73 m2 y 154 eran adultos sanos (Prevalencia= 17,01% (IC 95% 14,5%; 19,9%)). La mediana de la TFGe en la muestra completa fue de 85,53 ml/min/1,73 m² (IQR: 73,12-91,26). La prevalencia de la TFGe >80 ml/min/1,73 m2 fue mayor entre los hombres. En general, los adultos mayores sin factores de riesgo cardiovascular y con una TFGe >80 ml/min/1,73 m2 eran predominantemente hombres y mostraban una menor prevalencia de dislipidemia. Conclusiones: El presente estudio documentó que el 17% de los individuos mayores sanos tienen una tasa de filtración glomerular preservada (TFGe>80 ml/min/1,73 m2) a pesar de su avanzada edad.

The reduction of Cr(VI) in Salvinia minima, possible involvement of an h-type thioredoxin.

Hexavalent chromium [Cr(VI)] is extremely toxic to plant cells and has been recognized to possess a high redox potential. Tolerant plant species have shown the ability to reduce Cr(VI), but the operating mechanism involved in this process is not elucidated. Thus, the aim of this study was to investigate the possible involvement of thiolic and phenolic compounds and thioredoxin expression during Cr(VI) reduction in S. minima. In addition, a probable enzymatic reduction of Cr(VI) was investigated. Plants were exposed to 20 mg L-1 Cr(VI) concentration during 7 days under controlled conditions. The amount of metal accumulated in lacinias (root-like submerged leaves) and fronds (floating leaves) indicated that a low percentage of absorbed Cr(VI) was mobilized from lacinias to fronds. X-ray absorption near-edge structure (XANES) analysis revealed that Cr(III) was the only chromium species occurring in S. minima plants. Thiols and phenolics of lacinias and fronds were increased significantly by Cr(VI) treatment, but accumulation patterns were different. The expression of an h-type thioredoxin (Trx h) was demonstrated for the first time in Cr-exposed lacinias. Enzymatic reduction showed a low contribution to the Cr(VI) reduction. Data of this study provide evidences on the involvement of thiols, thioredoxin, and phenolics in the reduction of Cr(VI) to Cr(III) in S. minima tissues.

Implementación de la Iniciativa HEARTS en Argentina: primeros resultados / Implementation of the HEARTS Initiative in Argentina: initial results / Implementação da Iniciativa HEARTS na Argentina: primeiros resultados

RESUMEN Las enfermedades cardiovasculares son la principal causa de morbimortalidad, y la hipertensión es su principal factor de riesgo. En 2018, Argentina comenzó a implementar la Iniciativa HEARTS en 5 centros de atención primaria de salud a través del Plan Nacional de Prevención y Control de la Hipertensión Arterial. En este estudio se presenta el impacto de su implementación en los indicadores de cobertura efectiva, tratamiento, tratamiento combinado y control. La Iniciativa HEARTS incluye múltiples componentes; entre ellos se destacan la capacitación de los equipos de salud, la reorganización de las tareas basada en la transferencia de competencias clínicas, la provisión de dispositivos de medición de la presión arterial automáticos y clínicamente validados, y la utilización de un único protocolo de tratamiento estandarizado. Se utilizó un modelo de datos longitudinales del tipo ecuación de estimación generalizada, y se agrupó la información de los 5 centros de salud mediante promedios ponderados según el tamaño de la población bajo cobertura. El análisis de los resultados fue estratificado en dos períodos de tiempo delimitados por la irrupción de las restricciones debidas al COVID-19. Durante el primer período de 18 meses se observó una mejoría significativa en el tratamiento (5,9%; p<0,01) y el tratamiento combinado (13,4%; p<0,01), sin cambios significativos en la cobertura (8,4%; p=0,87) y con un descenso paradojal en el control (−3,3%; p=0,02). Durante las restricciones y respecto del período previo, se constató una reducción generalizada en todos los indicadores, principalmente en la cobertura (−23,6%; p<0,01) y el control (−12,5%; p<0,01). Sin embargo, los niveles de tratamiento y tratamiento combinado persistieron por encima de los valores basales (1,7%; p<0,01 y 5,4%; p<0,01, respectivamente).

ABSTRACT Cardiovascular diseases are the leading cause of mortality and morbidity in the Region of the Americas, and hypertension is one of the main risk factors. In 2018, Argentina began implementing the HEARTS Initiative in five primary health care centers, through the National Plan for the Prevention and Control of Arterial Hypertension. This study presents the impact its implementation has had on the indicators of effective coverage, treatment, combination therapy, and control. The HEARTS Initiative has multiple components; these include training health teams, reassigning tasks based on the transfer of clinical competencies, providing automatic and clinically validated blood pressure measurement devices, and using a single standardized treatment protocol. A longitudinal data model (generalized estimating equation analysis) was used, and the information from the five health centers was grouped using weighted averages according to the size of the population under coverage. Analysis of the results was stratified into two time periods delimited by the imposition of restrictions due to COVID-19. During the first period of 18 months, significant improvement was observed in treatment (5.9%; p<0.01) and combination therapy (13.4%; p<0.01), with no significant change in coverage (8.4%; p=0.87) and with a paradoxical decrease in control (−3.3%; p=0.02). When the period of restrictions was compared to the previous period, a generalized reduction was observed in all indicators, particularly coverage (−23.6%; p<0.01) and control (−12.5%; p<0.01). However, treatment and combination therapy levels remained above baseline values (1.7%; p<0.01 and 5.4%; p<0.01, respectively).

RESUMO As doenças cardiovasculares são a principal causa de morbimortalidade, e a hipertensão, seu principal fator de risco. Em 2018, a Argentina começou a implementar a Iniciativa HEARTS em 5 centros de atenção primária à saúde por meio do Plano Nacional de Prevenção e Controle da Hipertensão Arterial. Este estudo apresenta o impacto de sua implementação nos indicadores de cobertura efetiva, tratamento, tratamento combinado e controle. A Iniciativa HEARTS inclui vários componentes. Entre eles, se destacam a capacitação das equipes de saúde, a reorganização das tarefas com base na transferência de competências clínicas, a disponibilização de aparelhos automáticos e clinicamente validados para aferição da pressão arterial e a utilização de um único protocolo padronizado de tratamento. Foi utilizado um modelo de equações de estimativas generalizadas para a análise de dados longitudinais, e as informações dos 5 centros de saúde foram agrupadas por meio de médias ponderadas de acordo com o tamanho da população coberta. A análise dos resultados foi estratificada em dois períodos de tempo delimitados pela irrupção das restrições em virtude da COVID-19. Durante os primeiros 18 meses, houve melhora significativa no tratamento (5,9%; p<0,01) e no tratamento combinado (13,4%; p<0,01), sem mudança significativa na cobertura (8,4%; p=0,87) e com uma diminuição paradoxal no controle (−3,3%; p=0,02). Durante as restrições e em relação ao período anterior, verificou-se redução generalizada em todos os indicadores, principalmente na cobertura (−23,6%; p<0,01) e no controle (−12,5%; p<0,01). No entanto, os níveis de tratamento e tratamento combinado persistiram acima dos valores basais (1,7%; p<0,01 e 5,4%; p<0,01, respectivamente).

Dopaminergic stimulation leads B-cell infiltration into the central nervous system upon autoimmunity.

BACKGROUND: Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation of immune cells plays an important role in the physiopathology of inflammatory disorders. Multiple sclerosis (MS) is an inflammatory disease involving a CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models has suggested that B cells play a fundamental role as antigen-presenting cells (APC) re-stimulating CD4+ T cells in the CNS as well as regulating T-cell response by mean of inflammatory or anti-inflammatory cytokines. Here, we addressed the role of the dopamine receptor D3 (DRD3), which displays the highest affinity for dopamine, in B cells in animal models of MS. METHODS: Mice harbouring Drd3-deficient or Drd3-sufficient B cells were generated by bone marrow transplantation into recipient mice devoid of B cells. In these mice, we compared the development of experimental autoimmune encephalomyelitis (EAE) induced by immunization with a myelin oligodendrocyte glycoprotein (MOG)-derived peptide (pMOG), a model that leads to CNS-autoimmunity irrespective of the APC-function of B cells, or by immunization with full-length human MOG protein (huMOG), a model in which antigen-specific activated B cells display a fundamental APC-function in the CNS. APC-function was assessed in vitro by pulsing B cells with huMOG-coated beads and then co-culturing with MOG-specific T cells. RESULTS: Our data show that the selective Drd3 deficiency in B cells abolishes the disease development in the huMOG-induced EAE model. Mechanistic analysis indicates that although DRD3-signalling did not affect the APC-function of B cells, DRD3 favours the CNS-tropism in a subset of pro-inflammatory B cells in the huMOG-induced EAE model, an effect that was associated with higher CXCR3 expression. Conversely, the results show that the selective Drd3 deficiency in B cells exacerbates the disease severity in the pMOG-induced EAE model. Further analysis shows that DRD3-stimulation increased the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in the pMOG-induced EAE model. CONCLUSIONS: Our findings demonstrate that DRD3 in B cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B cells with APC-function and promoting CNS-homing of B cells with anti-inflammatory features. Thus, these results show DRD3-signalling in B cells as a critical regulator of CNS-autoimmunity.

Support surfaces for intraoperative pressure injury prevention: systematic review with meta-analysis.

OBJECTIVE: to evaluate evidence on effectiveness support surfaces for pressure injury prevention in the intraoperative period. METHOD: systematic review. The search for primary studies was conducted in seven databases. The sample consisted of 10 studies. The synthesis of the results was carried out descriptively and through meta-analysis. RESULTS: when comparing low-tech support surfaces with regular care (standard surgical table mattress), the meta-analysis showed that there is no statistically significant difference between the investigated interventions (Relative Risk = 0.88; 95%CI: 0.30-2.39). The Higgins inconsistency test indicated considerable heterogeneity between studies (I2 = 83%). The assessment of the certainty of the evidence was very low. When comparing high-tech and low-tech support surfaces, the meta-analysis showed that there is a statistically significant difference between the interventions studied, with high-tech being the most effective (Relative Risk = 0.17; 95%CI: 0.05-0.53). Heterogeneity can be classified as not important (I2 = 0%). The assessment of certainty of evidence was moderate. CONCLUSION: the use of high-tech support surfaces is an effective measure to prevent pressure injuries in the intraoperative period.

Effectiveness of financial incentives and message framing to improve clinic visits of people with moderate-high cardiovascular risk in a vulnerable population in Argentina: A cluster randomized trial.

In Argentina, cardiovascular disease (CVD) represents the first cause of mortality, but effective coverage for CVD prevention is low. Strategies based on behavioral economics are emerging worldwide as key pieces to increase the effectiveness of CVD prevention approaches. The aim of this study was to evaluate whether the implementation of two strategies based on financial incentives and framing increased attendance to clinical visits as proposed by the national program for CVD risk factors management among the uninsured and poor population with moderate or high CVD risk in Argentina. We conducted a cluster randomized trial in nine primary care clinics (PCCs) in Argentina. Three PCCs were assigned to financial incentives, 3 to framing-text messages (SMS) and 3 to usual care. The incentive scheme included a direct incentive for attending the first clinical visit and the opportunity to participate in a lottery when attending a second clinical visit. The framing-text messages group received messages with a gain-frame format. The main outcome was the proportion of participants who attended the clinical visits. A total of 918 individuals with a risk ≥10% of suffering a CVD event within the next 10 years were recruited to participate in the study. The financial incentive group had a significantly higher percentage of participants who attended the first (59.0% vs 33.9%, p˂ 0.001) and the follow up visit (34.4% and 16.6%, p˂ 0.001) compared to control group. However, the framing-SMS group did not show significant differences compared to the control group. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.govNCT03300154.

Assessment of the Streptomyces-plant system to mitigate the impact of Cr(VI) and lindane in experimental soils.

Phytoremediation techniques have been proposed as ecological methods to clean up contaminated sites. This study is aimed to evaluate the effect of the Streptomyces sp. Waksman & Henrici and Zea mays L. plant system on the dissipation of Cr(VI) and/or lindane from a co-contaminated soil, being 2 mg kg-1 of lindane and 150 mg kg-1 of chromium used. Lindane dissipation was improved in the presence of plant-microorganism association; however, Cr(VI) removal was higher when plants or the microorganism were separately. In co-contaminated systems, chromium content in plant tissues was lower than metal content in plants grown only with Cr(VI), suggesting that lindane could interfere with metal accumulation in the plant. The high malondialdehyde (MDA) concentration detected in non-inoculated plants grown with chromium could be consequence of high metal concentration in plant tissues. Interestingly, plants inoculated with Streptomyces sp. Z38 growing with Cr(VI) showed decrease in MDA concentration, indicating that the bacterium could activate defense mechanisms in the plant. Also, inoculated plants showed the highest value of superoxide dismutase activity. Lettuce plants used as bioindicators grew better in biologically treated soils compared with lettuce grown on non-treated soil. The results presented in this work provide the basis that will allow the optimization of future trials on a larger scale.

The analyst's presence: place and function of the body of the psychoanalyst in different contexts of action / A presença do analista: lugar e função do corpo do psicanalista em diferentes contextos de atuação

RESUMO: Com base nas propostas de Freud e Lacan, visamos tratar do lugar e da função do corpo do analista como condições para a sustentação da clínica. Para isso, destacamos quatro diferentes contextos de atuação: o consultório; o trabalho nos dispositivos das redes de saúde e assistência psicossocial; o acompanhamento terapêutico e atendimentos online. Pensando a clínica psicanalítica em termos de tática, estratégia e política, encontramos que o ato analítico seria norteado pela ética da psicanálise e assegurado na sustentação da posição do analista enquanto presença - ponto de convergência que permite a inserção do psicanalista nos campos de atuação citados.

Abstract: Based on the propositions of Freud and Lacan, we aim to approach the place and function of the analyst's body as conditions for the sustenance of the clinic. For this, we highlight four different work contexts: the clinic; public healthcare networks and psychosocial care; therapeutic accompaniment and online treatment. Thinking the psychoanalytic clinic in terms of tactic, strategy and politics, we found that the analytical act to be guided by the ethics of psychoanalysis and ensured in sustenance of the position of the analyst as a presence - a point of convergence that allows the insertion of the psychoanalyst in the aforementioned work contexts.

The Heteromeric Complex Formed by Dopamine Receptor D5 and CCR9 Leads the Gut Homing of CD4+ T Cells Upon Inflammation.

BACKGROUND AND AIMS: CD4+ T cells constitute central players in inflammatory bowel diseases (IBDs), driving inflammation in the gut mucosa. Current evidence indicates that CCR9 and the integrin α4ß7 are necessary and sufficient to imprint colonic homing on CD4+ T cells upon inflammation. Interestingly, dopaminergic signaling has been previously involved in leukocyte homing. Despite dopamine levels are strongly reduced in the inflamed gut mucosa, the role of dopamine in the gut homing of T cells remains unknown. Here, we study how dopaminergic signaling affects T cells upon gut inflammation. METHODS: Gut inflammation was induced by transfer of naïve T cells into Rag1-/- mice or by administration of dextran sodium sulfate. T cell migration and differentiation were evaluated by adoptive transfer of congenic lymphocytes followed by flow cytometry analysis. Protein interaction was studied by bioluminescence resonance energy transfer analysis, bimolecular fluorescence complementation, and in situ proximity ligation assays. RESULTS: We show the surface receptor providing colonic tropism to effector CD4+ T cells upon inflammation is not CCR9 but the complex formed by CCR9 and the dopamine receptor D5 (DRD5). Assembly of the heteromeric complex was demonstrated in vitro and in vivo using samples from mouse and human origin. The CCR9:DRD5 heteroreceptor was upregulated in the intestinal mucosa of IBD patients. Signaling assays confirmed that complexes behave differently than individual receptors. Remarkably, the disruption of CCR9:DRD5 assembly attenuated the recruitment of CD4+ T cells into the colonic mucosa. CONCLUSIONS: Our findings describe a key homing receptor involved in gut inflammation and introduce a new cell surface module in immune cells: macromolecular complexes formed by G protein-coupled receptors integrating the sensing of multiple molecular cues.

Border Environmental Justice PPGIS: Community-Based Mapping and Public Participation in Eastern Tijuana, México.

Community mapping projects have been studied as important contributions to the field of environmental justice and Public Participation Geographic Information Systems (PPGIS). As a collaborative project between the Colectivo Salud y Justicia Ambiental and Red de Ciudadanos por el Mejoramiento de las Comunidades (RECIMEC), the "Mapeo Comunitario de la Zona Alamar" was created as a mechanism for community participation in the urban planning process in Tijuana, México. This paper outlines the project's community mapping process, including planning, data collection, priority identification, and data submission. Results from this community mapping project are analyzed including the (1) particular environmental risks and goods in this border region, (2) the influence that the project data had on the urban planning process, and (3) the impact that the community mapping process had on community organizing capacity. Our findings point to particular environmental challenges in this border city including clandestine trash dumps, and contaminated water runoff points. The mapping project influenced the land use planning process by identifying the key environmental risks and goods to prioritize in the zoning and ground truthing urban planning data. The community mapping project also had a key impact on community organizing through the fomenting of knowledge and relationships between community members and government representatives at the city's urban planning agency.

The demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cells.

Dendritic cells (DCs) promote T-cell mediated tolerance to self-antigens and induce inflammation to innocuous-antigens. This dual potential makes DCs fundamental players in inflammatory disorders. Evidence from inflammatory colitis mouse models and inflammatory bowel diseases (IBD) patients indicated that gut inflammation in IBD is driven mainly by T-helper-1 (Th1) and Th17 cells, suggesting an essential role for DCs in the development of IBD. Here we show that GSK-J4, a selective inhibitor of the histone demethylase JMJD3/UTX, attenuated inflammatory colitis by reducing the inflammatory potential and increasing the tolerogenic features of DCs. Mechanistic analyses revealed that GSK-J4 increased activating epigenetic signals while reducing repressive marks in the promoter of retinaldehyde dehydrogenase isoforms 1 and 3 in DCs, enhancing the production of retinoic acid. This, in turn, has an impact on regulatory T cells (Treg) increasing their lineage stability and gut tropism as well as potentiating their suppressive activity. Our results open new avenues for the treatment of IBD patients.

Differential effects of Zn concentrations on Cr(VI) uptake by two Salvinia species: involvement of thiol compounds.

Floating ferns of the genus Salvinia have great potential for phytoremediation of heavy metals. To date, the effect of essential metals on the accumulation and transport of toxic metals by aquatic ferns has not been suitably established. The aim of this study was to compare the ability of floating leaves of Salvinia minima and Salvinia rotundifolia species to accumulate Cr from Cr(VI solutions containing very low (0.02 mg L-1) and low (5 mg L-1) Zn concentrations. After 7-day metal-exposure period, results showed that Zn increased Cr accumulation in S. minima leaves whereas in S. rotundifolia decreased significantly. Contrarily Zn accumulation did not show great differences between species. This fact may indicate that Zn interfere Cr(VI) uptake by S. rotundifolia. Bioconcentration factor (BCF) and translocation factor (TF) were affected differently by Zn in both Salvinia species. Membrane stability index (MSI) of both Salvinia species was decreased significantly by 5 mg L-1 Zn concentration. Zn ions also increased hydrogen peroxide accumulation in fronds of Salvinia species. Total thiols (TT), non-protein thiols (NPT) and protein-bound thiols (PBT) were differentially affected by Cr(VI) and Zn ions. This study provides evidences on the involvement of different mechanisms against Cr(VI)/Zn toxicity in S. minima and S rotundifolia species.

Dopaminergic signalling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation.

Evidence from inflammatory bowel diseases (IBD) patients and animal models has indicated that gut inflammation is driven by effector CD4+ T-cell, including Th1 and Th17. Conversely, Treg seem to be dysfunctional in IBD. Importantly, dopamine, which is abundant in the gut mucosa under homoeostasis, undergoes a sharp reduction upon intestinal inflammation. Here we analysed the role of the high-affinity dopamine receptor D3 (DRD3) in gut inflammation. Our results show that Drd3 deficiency confers a stronger immunosuppressive potency to Treg, attenuating inflammatory colitis manifestation in mice. Mechanistic analyses indicated that DRD3-signalling attenuates IL-10 production and limits the acquisition of gut-tropism. Accordingly, the ex vivo transduction of wild-type Treg with a siRNA for Drd3 induced a potent therapeutic effect abolishing gut inflammation. Thus, our findings show DRD3-signalling as a major regulator of Treg upon gut inflammation.