RESUMO
BACKGROUND: Hepatic encephalopathy (HE) is a common complication of cirrhosis associated with a reduced survival. The presence of high-flux spontaneous porto-systemic shunts can induce HE even in patients with preserved liver function. AIM: To evaluate the effect of spontaneous porto-systemic shunt embolization (SPSE) over HE and its long-term evolution. MATERIAL AND METHODS: Retrospective analysis of 11 patients (91% males) with severe HE non-responsive to medical treatment in whom a SPSE was performed. The grade of HE (employing West Haven score), survival, MELD and Child-Pugh score, ammonia levels, degree of disability (employing the modified Rankin scale (mRs)) were evaluated before and at thirty days after procedure. RESULTS: The most common etiology found was non-alcoholic steatohepatitis (63.6%). A reduction of at least two score points of HE was observed in all patients after thirty days. There was a significant reduction on median (IQR) West Haven score from 3 (2-3) at baseline to 1 (0-1) after the procedure (p < 0.01). Twelve months survival was 63.6%. There was a decrease in median ammonia level from 106.5 (79-165) (ug/dL) to 56 (43-61) after SPSE (p = 0.006). The median mRS score before and after the procedure was 3 (3-5) and 1 (1-2.5), respectively (p < 0.01). Conclusions: According to our experience, SPSE is a feasible and effective alternative to improve HE and functionality of patients with refractory EH.
Assuntos
Humanos , Masculino , Feminino , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/terapia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Amônia , Cirrose Hepática/complicaçõesRESUMO
OBJECTIVE: To determine the factors related to overall healthcare costs of road traffic accidents in Bucaramanga, Colombia. METHODS: A descriptive cross-sectional study was conducted through the analysis of road traffic accident records that took place in 2019 in Bucaramanga, Colombia. Cost quartiles in dollars were compared using Pearson's chi-squared and Fisher's exact tests. Odds ratios were also calculated in logistic regression. RESULTS: 3,150 road accidents were reported in 2019 involving 7,038 people, of which 812 had information related to healthcare costs in health care institutions. The median cost was 56.59 USD (RI = 29.35-140.15), average cost of 290.11 USD ± 731.22 (95%CI: 239.74-340.48). A higher possibility to be in the 4th quartile was found when persons were under 18 years of age (OR = 4.88; 95%CI: 1.30-18.32) or 46-60 years (OR = 3.66; 95%CI: 1.01-13.30), the type of vehicle involved is motorcycle (OR = 2.79; 95%CI: 1.25-6.24), bicycle (OR = 7.66; 95%CI: 2.70-21.68), having a head injury (OR = 4.50; 95%CI: 2.61-7.76) and hypothetical drunk driving (OR = 12.44; 95%CI: 2.01-76.87). CONCLUSIONS: Relevant factors in healthcare costs were riding a motorcycle or bicycle, having a head injury, being under 18 years of age or 46 to 60 years of age and hypothetical drunk driving. It is important to implement prevention measures based on identified factors to reduce road accident rate and therefore, its socioeconomic costs.
Assuntos
Acidentes de Trânsito , Traumatismos Craniocerebrais , Adolescente , Brasil/epidemiologia , Colômbia/epidemiologia , Estudos Transversais , Custos de Cuidados de Saúde , Humanos , Pessoa de Meia-IdadeRESUMO
Introduction: Public health risk management in Colombia is led by the Instituto Nacional de Salud. In the face of the COVID-19 emergency, response actions centered on the implementation of risk analysis rooms and the strengthening of surveillance at points of entry into the country. Objective: To analyze the implementation and maintenance phases of the COVID-19 risk analysis rooms in four border departments of Colombia. Materials and methods: We conducted a qualitative study of public health risk analysis rooms for COVID-19. We reviewed the documentation and data generated from March to June, 2020, in the departments of Amazonas, Vichada, Guainía, and Putumayo. We did semi-structured interviews with key actors and analyzed the answers using the NVivo plus version 11 application in three cycles: open coding, identification of emerging categories, and modeling by analyzing the identified strengths and weaknesses. Results: We identified the components of the incident command structure and the relationships between the public health areas. Strengths were evidenced in the integration of the areas: the management of information in real time, the border surveillance and the capabilities of rapid response teams, while weaknesses appeared in planning, community surveillance, and risk communication processes. Conclusions: Risk analysis rooms constitute a joint effort at the national and local levels which has promoted the articulated participation of all actors in the analysis of information and the optimization of an organized response during the COVID-19 pandemic.
Introducción. La gestión del riesgo de salud pública en Colombia es liderada por el Instituto Nacional de Salud. Ante la emergencia de la COVID-19, se articularon acciones de respuesta mediante salas de análisis del riesgo y se fortaleció la vigilancia en los puntos de entrada al país. Objetivo. Analizar las fases de implementación y mantenimiento de las salas de análisis del riesgo de COVID-19 en cuatro departamentos fronterizos de Colombia. Materiales y métodos. Se hizo un estudio cualitativo de salas de análisis del riesgo en salud pública para COVID-19. Se revisaron la documentación y los datos generados en el periodo de marzo a junio de 2020 en Amazonas, Vichada, Guainía y Putumayo, y se hicieron entrevistas semiestructuradas a personas clave, las cuales se analizaron con el aplicativo NVivo plus, versión 11, en tres ciclos: codificación abierta, establecimiento de categorías emergentes y modelación mediante el análisis de las debilidades y fortalezas detectadas. Resultados. Se determinaron los componentes de la estructura de comando de incidentes y las relaciones entre las áreas de salud pública. Se encontraron fortalezas en la integración de las áreas, el manejo de la información en tiempo real, la vigilancia en las fronteras y las capacidades de los equipos de respuesta inmediata. Se detectaron debilidades en los procesos de planeación, vigilancia comunitaria y comunicación del riesgo. Conclusiones. Las salas de análisis del riesgo constituyen un esfuerzo conjunto del nivel local y nacional que han promovido la participación articulada de los actores, para analizar la información y optimizar la respuesta organizada durante la pandemia de COVID-19.
Assuntos
COVID-19 , COVID-19/epidemiologia , Colômbia/epidemiologia , HumanosRESUMO
Introducción. La gestión del riesgo de salud pública en Colombia es liderada por el Instituto Nacional de Salud. Ante la emergencia de la COVID-19, se articularon acciones de respuesta mediante salas de análisis del riesgo y se fortaleció la vigilancia en los puntos de entrada al país. Objetivo. Analizar las fases de implementación y mantenimiento de las salas de análisis del riesgo de COVID-19 en cuatro departamentos fronterizos de Colombia. Materiales y métodos. Se hizo un estudio cualitativo de salas de análisis del riesgo en salud pública para COVID-19. Se revisaron la documentación y los datos generados en el periodo de marzo a junio de 2020 en Amazonas, Vichada, Guainía y Putumayo, y se hicieron entrevistas semiestructuradas a personas clave, las cuales se analizaron con el aplicativo NVivo plus, versión 11, en tres ciclos: codificación abierta, establecimiento de categorías emergentes y modelación mediante el análisis de las debilidades y fortalezas detectadas. Resultados. Se determinaron los componentes de la estructura de comando de incidentes y las relaciones entre las áreas de salud pública. Se encontraron fortalezas en la integración de las áreas, el manejo de la información en tiempo real, la vigilancia en las fronteras y las capacidades de los equipos de respuesta inmediata. Se detectaron debilidades en los procesos de planeación, vigilancia comunitaria y comunicación del riesgo. Conclusiones. Las salas de análisis del riesgo constituyen un esfuerzo conjunto del nivel local y nacional que han promovido la participación articulada de los actores, para analizar la información y optimizar la respuesta organizada durante la pandemia de COVID-19.
Introduction: Public health risk management in Colombia is led by the Instituto Nacional de Salud. In the face of the COVID-19 emergency, response actions centered on the implementation of risk analysis rooms and the strengthening of surveillance at points of entry into the country. Objective: To analyze the implementation and maintenance phases of the COVID-19 risk analysis rooms in four border departments of Colombia. Materials and methods: We conducted a qualitative study of public health risk analysis rooms for COVID-19. We reviewed the documentation and data generated from March to June, 2020, in the departments of Amazonas, Vichada, Guainía, and Putumayo. We did semi-structured interviews with key actors and analyzed the answers using the NVivo plus version 11 application in three cycles: open coding, identification of emerging categories, and modeling by analyzing the identified strengths and weaknesses. Results: We identified the components of the incident command structure and the relationships between the public health areas. Strengths were evidenced in the integration of the areas: the management of information in real time, the border surveillance and the capabilities of rapid response teams, while weaknesses appeared in planning, community surveillance, and risk communication processes. Conclusions: Risk analysis rooms constitute a joint effort at the national and local levels which has promoted the articulated participation of all actors in the analysis of information and the optimization of an organized response during the COVID-19 pandemic.
Assuntos
Infecções por Coronavirus/epidemiologia , Gestão de Riscos , Controle Sanitário de Fronteiras , PandemiasRESUMO
INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.
Assuntos
Doença de Alzheimer , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/metabolismo , Cognição , Colômbia , Testes Neuropsicológicos , Presenilina-1/genética , Caracteres SexuaisRESUMO
BACKGROUND: Hepatic encephalopathy (HE) is a common complication of cirrhosis associated with a reduced survival. The presence of high-flux spontaneous porto-systemic shunts can induce HE even in patients with preserved liver function. AIM: To evaluate the effect of spontaneous porto-systemic shunt embolization (SPSE) over HE and its long-term evolution. MATERIAL AND METHODS: Retrospective analysis of 11 patients (91% males) with severe HE non-responsive to medical treatment in whom a SPSE was performed. The grade of HE (employing West Haven score), survival, MELD and Child-Pugh score, ammonia levels, degree of disability (employing the modified Rankin scale (mRs)) were evaluated before and at thirty days after procedure. RESULTS: The most common etiology found was non-alcoholic steatohepatitis (63.6%). A reduction of at least two score points of HE was observed in all patients after thirty days. There was a significant reduction on median (IQR) West Haven score from 3 (2-3) at baseline to 1 (0-1) after the procedure (p < 0.01). Twelve months survival was 63.6%. There was a decrease in median ammonia level from 106.5 (79-165) (ug/dL) to 56 (43-61) after SPSE (p = 0.006). The median mRS score before and after the procedure was 3 (3-5) and 1 (1-2.5), respectively (p < 0.01). CONCLUSIONS: According to our experience, SPSE is a feasible and effective alternative to improve HE and functionality of patients with refractory EH.
Assuntos
Encefalopatia Hepática , Derivação Portossistêmica Transjugular Intra-Hepática , Masculino , Humanos , Feminino , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/terapia , Estudos Retrospectivos , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Amônia , Resultado do Tratamento , Cirrose Hepática/complicaçõesRESUMO
OBJECTIVE: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer's disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world's largest ADAD kindred and sex differences in the relationship between SCD and memory performance. METHODS: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. RESULTS: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. CONCLUSIONS: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/complicações , Disfunção Cognitiva/psicologia , Estudos de Coortes , Colômbia , Feminino , Heterozigoto , Humanos , Masculino , Testes Neuropsicológicos , Fatores SexuaisRESUMO
ABSTRACT OBJECTIVE To determine the factors related to overall healthcare costs of road traffic accidents in Bucaramanga, Colombia. METHODS A descriptive cross-sectional study was conducted through the analysis of road traffic accident records that took place in 2019 in Bucaramanga, Colombia. Cost quartiles in dollars were compared using Pearson's chi-squared and Fisher's exact tests. Odds ratios were also calculated in logistic regression. RESULTS 3,150 road accidents were reported in 2019 involving 7,038 people, of which 812 had information related to healthcare costs in health care institutions. The median cost was 56.59 USD (RI = 29.35-140.15), average cost of 290.11 USD ± 731.22 (95%CI: 239.74-340.48). A higher possibility to be in the 4th quartile was found when persons were under 18 years of age (OR = 4.88; 95%CI: 1.30-18.32) or 46-60 years (OR = 3.66; 95%CI: 1.01-13.30), the type of vehicle involved is motorcycle (OR = 2.79; 95%CI: 1.25-6.24), bicycle (OR = 7.66; 95%CI: 2.70-21.68), having a head injury (OR = 4.50; 95%CI: 2.61-7.76) and hypothetical drunk driving (OR = 12.44; 95%CI: 2.01-76.87). CONCLUSIONS Relevant factors in healthcare costs were riding a motorcycle or bicycle, having a head injury, being under 18 years of age or 46 to 60 years of age and hypothetical drunk driving. It is important to implement prevention measures based on identified factors to reduce road accident rate and therefore, its socioeconomic costs.
RESUMEN OBJETIVO Determinar los factores relacionados con los costos generales durante la atención en salud de siniestros de tránsito en Bucaramanga, Colombia. MÉTODOS Estudio descriptivo, transversal, con análisis de registros de siniestros de tránsito durante 2019 en Bucaramanga, Colombia. Se realizó una comparación entre cuartiles de los costos en dólares con pruebas estadísticas de Chi-cuadrado de Pearson y exacta de Fisher. También, se calcularon odds ratio en regresión logística. RESULTADOS En 2019 se registraron 3.150 siniestros, con 7.038 personas involucradas, de los cuales 812 tenían información de costos generados por atención en instituciones de salud. La mediana de costos fue US$ 56,59 (RI = 29,35-140,15), promedio de US$ 290,11 ± 731,22 (IC95% 239,74-340,48). Se observó mayor posibilidad para estar en cuartil 4 de los costos si la persona tenía menos de 18 años (OR = 4,88; IC95% 1,30-18,32) o entre los 46-60 años de edad (OR = 3,66; IC95% 1,01-13,30), cuando el tipo de vehículo es la motocicleta (OR = 2,79; IC95% 1,25-6,24) y la bicicleta (OR = 7,66; IC95% 2,70-21,68), si la lesión ocurre en la cabeza (OR = 4,50; IC95% 2,61-7,76) y si la hipótesis está relacionada con embriaguez (OR = 12,44; IC95% 2,01-76,87). CONCLUSIÓN Los factores relevantes en los costos fueron la motocicleta, bicicleta, lesión en la cabeza, ser menor de 18 años o tener entre los 46 años y los 60 años y embriaguez como hipótesis. Es relevante implementar medidas de prevención según los factores identificados para disminuir la accidentalidad y, por ende, sus costos socioeconómicos.
Assuntos
Humanos , Adolescente , Pessoa de Meia-Idade , Acidentes de Trânsito , Traumatismos Craniocerebrais , Brasil/epidemiologia , Estudos Transversais , Custos de Cuidados de Saúde , Colômbia/epidemiologiaRESUMO
Neuropsychologists continue to face challenges when assessing Spanish-speaking individuals due to limited availability of normative data. We developed comprehensive normative data stratified by age and education for a Spanish neuropsychological test battery used by the Grupo de Neurociencias de Antioquia (Colombia) and the Colombian Alzheimer's Prevention Initiative Registry, which have followed large families at risk for autosomal-dominant Alzheimer's disease (ADAD) since the 1990s. Approximately 75% of these individuals are cognitively-unimpaired and are not genetically predisposed to develop ADAD. We conducted a retrospective study on neuropsychological evaluations from 2,673 cognitively unimpaired individuals (56% female), with ages ranging from 18 to 86 years and education from 1 to 25 years. Neuropsychological measures included the Consortium to Establish a Registry for Alzheimer's Disease-Colombia, and other multidomain Spanish tests. We examined associations between age, education, and sex with cognitive performance. Norms stratified by age and education are presented. Cognitive performance showed small associations with age and education and was unrelated to sex. We provided population-based norms for Spanish tests targeting multiple cognitive domains using a large Colombian sample. These normative data may be helpful for the neuropsychological characterization of Spanish speakers from Latin America in clinical and research settings.
Assuntos
Doença de Alzheimer , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Colômbia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valores de Referência , Sistema de Registros , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Growing evidence suggests that there may be a sex-specific biological risk for Alzheimer's disease (AD). Individuals with autosomal dominant AD due to a mutation (E280A) in Presenilin-1 (PSEN1) are genetically determined to develop early-onset dementia and thus, have few age-related risk factors for AD that are known to vary by sex (i.e., cardiovascular disease, menopause, life expectancy). OBJECTIVE: Investigate sex differences in markers of cognition and neurodegeneration in autosomal dominant AD. METHODS: We conducted a retrospective study in 19 cognitively-unimpaired PSEN1 mutation carriers (age range 20-44; 11 females), 11 symptomatic carriers (age range 42-56; 8 females), and 23 matched non-carriers family members (age range 20-50; 13 females). We examined hippocampal volume ratio, CERAD Total Score, and CERAD Word List (i.e., Learning, Delayed Recall, and Recognition). Mann-Whitney U tests, Spearman correlations and regression models were conducted. RESULTS: There were no differential associations between age, CERAD Total Score, CERAD Word List-Learning, Delayed Recall, Recognition, and hippocampal volume ratio in male and female carriers and non-carriers. Cognitively-unimpaired female carriers showed better CERAD Total scores and CERAD Word List-Learning than cognitively-unimpaired male carriers, despite having similar hippocampal volume ratios. The interaction of sex and hippocampal volume ratio did not predict cognitive performance across groups. CONCLUSION: Our preliminary findings suggest that cognitively-unimpaired female carriers showed a verbal memory reserve, and as disease progresses, female carriers did not exhibit a cognitive susceptibility to AD-related neurodegeneration. Future studies with larger samples of autosomal dominant AD are warranted to further understand sex differences in AD-related clinical and pathological markers.
Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Cognição/fisiologia , Presenilina-1/genética , Caracteres Sexuais , Adulto , Doença de Alzheimer/psicologia , Biomarcadores , Colômbia/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/psicologia , Testes Neuropsicológicos , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêutico , Cognição/fisiologia , Mutação , Presenilina-1/genética , Adulto , Doença de Alzheimer/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Halites, which are typically found in various Atacama locations, are evaporitic rocks that are considered as micro-scaled salterns. Both structural and functional metagenomic analyses of halite nodules were performed. Structural analyses indicated that the halite microbiota is mainly composed of NaCl-adapted microorganisms. In addition, halites appear to harbor a limited diversity of fungal families together with a biodiverse collection of protozoa. Functional analysis indicated that the halite microbiome possesses the capacity to make an extensive contribution to carbon, nitrogen, and sulfur cycles, but possess a limited capacity to fix nitrogen. The halite metagenome also contains a vast repertory of carbohydrate active enzymes (CAZY) with glycosyl transferases being the most abundant class present, followed by glycosyl hydrolases (GH). Amylases were also present in high abundance, with GH also being identified. Thus, the halite microbiota is a potential useful source of novel enzymes that could have biotechnological applicability. This is the first metagenomic report of fungi and protozoa as endolithobionts of halite nodules, as well as the first attempt to describe the repertoire of CAZY in this community. In addition, we present a comprehensive functional metagenomic analysis of the metabolic capacities of the halite microbiota, providing evidence for the first time on the sulfur cycle in Atacama halites.
RESUMO
Cardiac fibroblasts (CFs) contribute to theinflammatory response to tissue damage, secreting both pro- and anti-inflammatory cytokines and chemokines. Interferon beta (IFN-ß) induces the phosphorylation of signal transducer and activator of transcription (STAT) proteins through the activation of its own receptor, modulating the secretion of cytokines and chemokines which regulate inflammation. However, the role of IFN-ß and STAT proteins in modulating the inflammatory response of CF remains unknown. CF were isolated from adult male rats and subsequently stimulated with IFN-ß to evaluate the participation of STAT proteins in secreting chemokines, cytokines, cell adhesion proteins expression and in their capacity to recruit neutrophils. In addition, in CF in which the TRL4 receptor was pre-activated, the effect of INF-ß on the aforementioned responses was also evaluated. Cardiac fibroblasts stimulation with IFN-ß showed an increase in STAT1, STAT2, and STAT3 phosphorylation. IFN-ß stimulation through STAT1 activation increased proinflammatory chemokines MCP-1 and IP-10 secretion, whereas IFN-ß induced activation of STAT3 increased cytokine secretion of anti-inflammatory IL-10. Moreover, in TLR4-activated CF, IFN-ß through STAT2 and/or STAT3, produced an anti-inflammatory effect, reducing pro-IL-1ß, TNF-α, IL-6, MCP-1, and IP-10 secretion; and decreasing neutrophil recruitment by decreasing ICAM-1 and VCAM-1 expression. Altogether, our results indicate that IFN-ß exerts both pro-inflammatory and anti-inflammatory effects in non-stimulated CF, through differential activation of STAT proteins. When CF were previously treated with an inflammatory agent such as TLR-4 activation, IFN-ß effects were predominantly anti-inflammatory.
RESUMO
BACKGROUND: There is a need to find cognitive markers that can help identify individuals at risk for Alzheimer's disease (AD), and that can be used to reliably measure cognitive decline. OBJECTIVE: We tested whether a theoretically driven three-factor structure would characterize cognitive functioning in individuals who are genetically-determined to develop AD due to a mutation in Presenilin-1 (PSEN1) gene. We also examined whether these factors could distinguish cognitively unimpaired PSEN1 mutation carriers from age-matched non-carrier family members. METHODS: 1,395 cognitively unimpaired members of a Colombian kindred with the PSEN1 E280A mutation were included in the study. A confirmatory factor analysis examined the fit of the three-factor model comprising episodic memory (MMSE memory recall, CERAD-COL Word list recall, and Constructional praxis recall), executive function (Phonemic fluency and WCST perseverative errors), and psychomotor processing speed (TMT-A and WAIS-III Digit Symbol). RESULTS: The three-factor model provided an excellent fit for all participants (p = 0.24; RMSEA = 0.01). Further, the episodic memory (p = 0.0004, d = 0.25) and executive functioning (p = 0.001, d = 0.18) factors distinguished cognitively unimpaired carriers from non-carriers. The episodic memory factor provided the earliest indication of preclinical cognitive decline at 35 years of age, nine years before individuals' estimated age of clinical onset. CONCLUSIONS: The three theoretically derived cognitive factors provide a reliable measure of cognition and may be useful for the early detection of AD, as well as for measuring disease progression. However, longitudinal studies are needed to confirm that these factors can be used to track the progression of cognitive decline in preclinical AD.
Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Disfunção Cognitiva/etiologia , Mutação/genética , Presenilina-1/genética , Adolescente , Adulto , Colômbia , Função Executiva/fisiologia , Análise Fatorial , Feminino , Humanos , Masculino , Memória Episódica , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Adulto JovemRESUMO
Cardiac fibroblasts (CF) act as sentinel cells responding to chemokines, cytokines and growth factors released in cardiac tissue in cardiac injury events, such as myocardial infarction (MI). Cardiac injury involves the release of various damage-associated molecular patterns (DAMPs) including heparan sulfate (HS), a constituent of the extracellular matrix (ECM), through the TLR4 receptor activation triggering a strong inflammatory response, inducing leukocytes recruitment. This latter cells are responsible of clearing cell debris and releasing cytokines that promote CF differentiation to myofibroblast (CMF), thus initiating scar formation. CF were isolated from adult male rats and subsequently stimulated with HS or LPS, in the presence or absence of chemical inhibitors, to evaluate signaling pathways involved in ICAM-1 and VCAM-1 expression. siRNA against ICAM-1 and VCAM-1 were used to evaluate participation of these adhesion molecules on leukocytes recruitment. HS through TLR4, PI3K/AKT and NF-ΚB increased ICAM-1 and VCAM-1 expression, which favored the adhesion of spleen mononuclear cells (SMC) and bone marrow granulocytes (PMN) to CF. These effects were prevented by siRNA against ICAM-1 and VCAM-1. Co-culture of CF with SMC increased α-SMA expression, skewing CF towards a pro-fibrotic phenotype, while CF pretreatment with HS partially reverted this effect. CONCLUSION: These data show the dual role of HS during the initial stages of wound healing. Initially, HS enhance the pro-inflammatory role of CF increasing cytokines secretion; and later, by increasing protein adhesion molecules allows the adhesion of SMC on CF, which trigger CF-to-CMF differentiation.
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Adesão Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Heparitina Sulfato/farmacologia , Molécula 1 de Adesão Intercelular/metabolismo , Leucócitos/efeitos dos fármacos , Miocárdio/citologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Células Cultivadas , Fibroblastos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/genética , Leucócitos/fisiologia , Masculino , Miocárdio/metabolismo , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Molécula 1 de Adesão de Célula Vascular/genéticaAssuntos
Antibacterianos/uso terapêutico , Antituberculosos/uso terapêutico , Mastite/diagnóstico , Tuberculose Cutânea/diagnóstico , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Isoniazida/uso terapêutico , Mastite/microbiologia , Mastite/patologia , Pele/patologia , Tuberculose Cutânea/microbiologia , Tuberculose Cutânea/patologiaRESUMO
RESUMEN Objetivo: Asociar el nivel de conocimiento y prácticas (hábitos y costumbres) responsables de la transmisión de Triquinelosis, Síndrome Cardiopulmonar por Hantavirus y Equinococosis quística (Hidatidosis), en habitantes de los sectores rurales. Material y método: Estudio descriptivo correlacional de corte transversal en el que se aplicó una encuesta a 149 habitantes residentes en el área rural de las localidades de Curacautín, Lonquimay y Melipeuco, a través de muestreo no probabilístico por conveniencia, durante los meses de diciembre 2013 a enero 2014. Resultados: La población posee mejores conocimientos de Triquinelosis y Hanta que Hidatidosis, 64,9, 72,8 y 39,3%, respectivamente; los hábitos y costumbres para Hanta e Hidatidosis alcanzan mejores prácticas (84% cada una) que para Triquinelosis (69,5%); la población reconoce correctamente reservorio, fuente de infección y mecanismos de transmisión en Triquinelosis y Hanta, pero en menor grado Hidatidosis; respecto de los hábitos y costumbres, aun desconociendo los fundamentos teóricos, reportan buenas prácticas, aunque mantienen algunas que favorecen la transmisión de infecciones predominantemente en Triquinelosis. Conclusión: El nivel de conocimiento no asegura buenas prácticas, además los conocimientos y prácticas siguen un patrón empírico más que cognitivo, respaldados por aspectos culturales y del entorno. Esto sugiere mayor participación de los equipos interdisciplinarios en comunidades aisladas para fortalecer la promoción, educación y refuerzo de las buenas prácticas de acuerdo con sus condiciones sociales e incentivar la adherencia a conductas que reduzcan el riesgo de la transmisión de zoonosis.
ABSTRACT Objective: To associate the level of knowledge and practices (habits and customs) responsible for the transmission of trichinellosis, Hanta and cystic echinococcosis (hydatidosis), among rural population. Material and method: Cross-sectional correlational descriptive study in which 149 residents of the rural areas of Curacautín, Lonquimay and Melipeuco were surveyed, using non-probability convenience sampling from December 2013 to January 2014. Results: The population has better knowledge of trichinellosis and Hanta than hydatidosis, 64.9%, 72.8 and 39.3% respectively; they also have better practices regarding Hanta and hydatidosis (84% each) than regarding trichinellosis (69.5%). The population recognizes correctly the reservoir, source of infection and transmission mechanisms of trichinellosis and Hanta, and to a lesser degree hydatidosis; they report good practices regarding habits and customs, even ignoring theoretical foundations, but maintain some practices that favor the transmission of infections related to trichinellosis. Conclusion: The level of knowledge does not ensure good practices. Additionally, knowledge and practices follow an empirical rather than cognitive pattern, rooted on cultural and environmental aspects. This suggests greater participation of interdisciplinary teams in isolated communities to strengthen the promotion, education and reinforcement of good practices in accordance with their social conditions and to encourage adherence to behaviors that reduce the risk of the transmission of zoonoses.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , População Rural , Triquinelose/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Hantavirus/prevenção & controle , Equinococose/prevenção & controle , Fatores Socioeconômicos , Triquinelose/transmissão , Zoonoses/prevenção & controle , Zoonoses/transmissão , Chile , Estudos Transversais , Grupos Focais , Infecções por Hantavirus/transmissão , Equinococose/transmissãoRESUMO
Bacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-ß1 (TGF-ß1), increasing alpha-smooth muscle actin (α-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-ß1 signaling was described; however, it has not been studied whether in CF and CMF the expression of α-SMA induced by TGF-ß1 is antagonized by LPS and the mechanism involved. In adult rat CF and CMF, α-SMA, ERK1/2, Akt, NF-κß, Smad3, and Smad7 protein levels were determined by western blot, TGF-ß isoforms by ELISA, and α-SMA stress fibers by immunocytochemistry. CF and CMF secrete the three TGF-ß isoforms, and the secretion levels of TGF-ß2 was affected by LPS treatment. In CF, LPS treatment decreased the protein levels of α-SMA, and this effect was prevented by TAK-242 (TLR4 inhibitor) and LY294002 (Akt inhibitor), but not by BAY 11-7082 (NF-κß inhibitor) and PD98059 (ERK1/2 inhibitor). TGF-ß1 increased α-SMA protein levels in CF, and LPS prevented partially this effect. In addition, in CMF α-SMA protein levels were decreased by LPS treatment, which was abolished by TAK-242. Finally, in CF LPS decreased the p-Smad3 phosphorylation and increased the Smad7 protein levels. LPS treatment prevents the CF-to-CMF differentiation and reverses the CMF phenotype induced by TGF-ß1, through decreasing p-Smad3 and increasing Smad7 protein levels.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Masculino , Miócitos Cardíacos/fisiologia , Miofibroblastos/fisiologia , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/agonistasRESUMO
Macrophage polarization plays an essential role in cardiac remodeling after injury, evolving from an initial accumulation of proinflammatory M1 macrophages to a greater balance of anti-inflammatory M2 macrophages. Whether cardiac fibroblasts themselves influence this process remains an intriguing question. In this work, we present evidence for a role of cardiac fibroblasts (CF) as regulators of macrophage recruitment and skewing. Adult rat CF, were treated with lipopolysaccharide (LPS) or TGF-ß1, to evaluate ICAM-1 and VCAM-1 expression using Western blot and proinflammatory/profibrotic cytokine secretion using LUMINEX. We performed in vitro migration and adhesion assays of rat spleen monocytes to layers of TGF-ß1- or LPS-pretreated CF. Finally, TGF-ß1- or LPS-pretreated CF were co-cultured with monocyte, to evaluate their effects on macrophage polarization, using flow cytometry and cytokine secretion. There was a significant increase in monocyte adhesion to LPS- or TGF-ß1-stimulated CF, associated with increased CF expression of ICAM-1 and VCAM-1. siRNA silencing of either ICAM-1 or VCAM-1 inhibited monocyte adhesion to LPS-pretreated CF; however, monocyte adhesion to TGF-ß1-treated CF was dependent on only VCAM-1 expression. Pretreatment of CF with LPS or TGF-ß1 increased monocyte migration to CF, and this effect was completely abolished with an MCP-1 antibody blockade. LPS-treated CF secreted elevated levels of TNF-α and MCP-1, and when co-cultured with monocyte, LPS-treated CF stimulated increased macrophage M1 polarization and secretion of proinflammatory cytokines (TNF-α, IL-12 and MCP-1). On the other hand, CF stimulated with TGF-ß1 produced an anti-inflammatory cytokine profile (high IL-10 and IL-5, low TNF-α). When co-cultured with monocytes, the TGF-ß1 stimulated fibroblasts skewed monocyte differentiation towards M2 macrophages accompanied by increased IL-10 and decreased IL-12 levels. Taken together, our results show for the first time that CF can recruit monocytes (via MCP-1-mediated chemotaxis and adhesion to ICAM-1/VCAM-1) and induce their differentiation to M1 or M2 macrophages (through the CF cytokine profile induced by proinflammatory or profibrotic stimuli).