RESUMO
INTRODUCTION: In parallel with the obesity and diabetes epidemics, steatotic liver disease (SLD) has emerged as a major global public health concern. The mainstay of therapy is counseling on weight loss and increased exercise. However, such lifestyle modifications infrequently lead to success. We aimed to identify barriers to diet and lifestyle modification in patients with SLD. METHODS: Patients with SLD completed a 14-item questionnaire that assigned barriers to healthy eating to three categories: lack of knowledge, lack of self-control, and lack of time, with a higher summary score indicating more perceived barriers. We administered assessments of health literacy and physical activity. We analyzed the data using descriptive statistics and ordinal regression analysis. RESULTS: We included 151 participants with a median age of 64; 54% were female and 68.2% were Hispanic. Median BMI was 31.9 kg/m2. Most respondents, 68.2%, had low health literacy and were either underactive, 29.1% or sedentary, 23.2%. Lack of self-control was the strongest barrier to achieving a healthy lifestyle, followed by lack of knowledge. Lack of time was not significant barrier. Patients with the most significant barriers were more likely to have obesity, low health literacy, and be sedentary. DISCUSSION: Lack of self-control and knowledge are the greatest barriers to adopting a healthy lifestyle in patients with SLD. Future clinical interventions should integrate education that targets various health literacy levels with behavioral approaches to improve a sense of agency.
Assuntos
Fígado Gorduroso , Letramento em Saúde , Autocontrole , Humanos , Feminino , Masculino , Obesidade/epidemiologia , Estilo de Vida Saudável , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/terapiaRESUMO
The transcription factor E-twenty-six variant 5 (ETV5) regulates acute insulin secretion. Adequate insulin secretion is dependent on pancreatic ß-cell size and cell proliferation, but the effects of ETV5 on proliferation, cell number, and viability, as well as its relationship with insulin secretion, have not been established yet. Here, we partially silenced ETV5 in the INS-1 (832/13) cell line by siRNA transfection and then measured secreted insulin concentration at different time points, observing similar levels to control cells. After 72 h of ETV5 silencing, we observed decreased cell number and proliferation, without any change in viability or apoptosis. Thus, partial silencing of ETV5 modulates cell proliferation in INS-1 (832/13) independently of secreted insulin levels via upregulation of E2F1 and of inhibitors of the cyclin/CDKs complexes (p21Cdkn1a , p27Cdkn1b , and p57Cdkn1c ) and downregulation of cell cycle activators (PAK3 and FOS).
Assuntos
Genes cdc , Insulina , Animais , Ratos , Divisão Celular , Linhagem Celular , Proliferação de Células/genética , Insulina/genética , Insulina/metabolismoRESUMO
The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hematooncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.
La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.
Assuntos
Neutropenia Febril , Fusariose , Neoplasias , Humanos , Fusariose/tratamento farmacológico , Fusariose/etiologia , Antifúngicos/uso terapêutico , Pesquisa , Neoplasias/complicaçõesRESUMO
La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.
The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hemato-oncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.
Assuntos
Fusarium , Anfotericina B , Fungemia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , VoriconazolRESUMO
Introduction: Bacterial agents and oxidative reactions are involved in health and food preservation issues, and Yucca baccata (Y. baccata) can be a source of compounds with practical applications in both areas, but its investigation remains limited. Materials and Methods: Butanolic (YBE) and aqueous (YAE) extracts were obtained from the stem of Y. baccata. The total saponin, phenolic, and flavonoid contents were analyzed in the YBE and YAE. The antioxidant capacity of the extracts was determined by the DPPH, TEAC, FRAP, and ORAC assays. Seven Gram-positive and five Gram-negative pathogenic bacteria strains were used to determine the MIC and MBC. Results: Saponin contents were 30% and 1.81% (w/w) in the YBE and YAE, respectively. The total phenolic and flavonoid contents in the extracts were 29.5 µg GAEmg-1 (2.95%) and 5.58 µg GAEmg-1 (0.56%) in the YBE and 69.92 µg QEmg-1 (7.0%) and 1.65 µg QEmg-1 (0.165%) in the YAE. The antioxidant capacity values of YBE were 29.18 µg TEmg-1, 121.8 µg TEmg-1, 33.41 µg TEmg-1, and 156.84 µg TEmg-1 by the DPPH, TEAC, FRAP, and ORAC assays, respectively. YAE had lower antioxidant values than YBE (P < 0.05). Values of 80 mgmL-1 and 100 mgmL-1 were estimated for MIC and MBC of YBE against the Gram-positive bacteria. Values of 100 mgmL-1 and 120 mgmL-1 for MIC and MBC of YBE were estimated against the Gram-negative bacteria. No MIC and MBC were obtained for YAE. Conclusion: YBE exhibited higher antioxidant activity than YAE. Apparently, antibacterial properties of the YBE tended to be higher than those of the YAE.
Assuntos
Saponinas , Yucca , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , México , Bactérias , Antibacterianos/farmacologia , Flavonoides/farmacologia , Fenóis/farmacologia , Fenóis/análise , Testes de Sensibilidade MicrobianaRESUMO
Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged the development of effective pharmacological treatments to directly attack the development of new variants of the SARS-CoV-2 virus and possess a therapeutical battery of compounds that could improve the current management of the disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, and potentially antiviral mechanisms, is an interesting proposal as an adjuvant in the treatment of COVID-19 patients. Nevertheless, it is essential to understand how this compound could behave against such a disease, not only at a pharmacodynamic but also at a pharmacokinetic level. In this sense, the quickest approach in drug discovery is through different computational methods, either from network pharmacology or from quantitative systems pharmacology approaches. In the present review, we explore the possibility of using theophylline in the treatment of COVID-19 patients since it seems to be a relevant candidate by aiming at several immunological targets involved in the pathophysiology of the disease. Theophylline down-regulates the inflammatory processes activated by SARS-CoV-2 through various mechanisms, and herein, they are discussed by reviewing computational simulation studies and their different applications and effects.
Assuntos
Tratamento Farmacológico da COVID-19 , Antivirais/farmacocinética , Antivirais/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Pandemias , SARS-CoV-2 , Teofilina/farmacologia , Teofilina/uso terapêuticoRESUMO
The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Caffeine has been proven to be an effective anti-inflammatory and immunomodulator. In airway smooth muscle, it has bronchodilator effects mainly due to its activity as a phosphodiesterase inhibitor and adenosine receptor antagonist. In addition, a recent published document has suggested the potential antiviral activity of this drug using in silico molecular dynamics and molecular docking; in this regard, caffeine might block the viral entrance into host cells by inhibiting the formation of a receptor-binding domain and the angiotensin-converting enzyme complex and, additionally, might reduce viral replication by the inhibition of the activity of 3-chymotrypsin-like proteases. Here, we discuss how caffeine through certain mechanisms of action could be beneficial in SARS-CoV-2. Nevertheless, further studies are required for validation through in vitro and in vivo models.
Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , COVID-19/dietoterapia , Cafeína/farmacologia , Reposicionamento de Medicamentos/métodos , Músculo Liso/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , COVID-19/metabolismo , COVID-19/fisiopatologia , Humanos , Fatores Imunológicos/farmacologia , Simulação de Dinâmica Molecular , Músculo Liso/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismoRESUMO
Objetivo.En la Región de las Américas se han realizado pocas evaluaciones de redes integradas de servicios de salud (RISS). Honduras ha avanzado en la implementación de herramientas y estrategias basadas en los atributos esenciales de las RISS. Este estudio tiene como objetivo valorar y comparar el desarrollo de RISS en su planteamiento teórico-documental y en su aplicación práctica, por tipo de gestión, en cinco redes de Honduras. Métodos. El estudio se realizó en dos etapas: 1) valoración teórico-documental, mediantela revisión y síntesis de seis documentos oficiales de RISS publicados entre 2012 y 2017, y 2) valoración práctica con los equipos de coordinación de cinco redes, dos descentralizadas y tres mixtas, usando la Herramienta de Valoración de RISS de la Organización Panamericana de la Salud. Resultados. La valoración teórica global alcanzó 55 puntos de desarrollo comparada con la valoración práctica de las cinco redes, que alcanzó 42,8. Según el análisis por ámbitos, el Modelo asistencial obtuvo mejores resultados en ambas valoraciones, mayor en la valoración teórica (62,5). Gobernanza y estrategia fue elámbito que recibió la valoración más baja(41,7). Entre lavaloración teórica y lapráctica las diferencias en el análisis deámbitos y de atributos fueron estadísticamente significativas(p=0,007yp<0,001,respectivamente).Las redes con gestión descentralizada alcanzaron mejores valoraciones que las mixtas(p=0,017). Conclusiones. Existe una brecha entre la valoración teórica y la práctica que sugiere que la aplicación de las herramientas y las estrategias definidas en los documentos son incompletas. El componente provisional sigue siendo el que genera mayor interé se importancia. Enlasredes mixtas se observó mayor dificultad de integración, probablemente debido al a doble gobernanza. Es necesario seguir evaluando las RISS...(AU)
Assuntos
Humanos , Qualidade, Acesso e Avaliação da Assistência à Saúde , Benchmarking , Sistemas Nacionais de Saúde , Indicadores Básicos de SaúdeRESUMO
[RESUMEN]. Objetivo. En la Región de las Américas se han realizado pocas evaluaciones de redes integradas de servicios de salud (RISS). Honduras ha avanzado en la implementación de herramientas y estrategias basadas en los atributos esenciales de las RISS. Este estudio tiene como objetivo valorar y comparar el desarrollo de RISS en su planteamiento teórico-documental y en su aplicación práctica, por tipo de gestión, en cinco redes de Honduras. Métodos. El estudio se realizó en dos etapas: 1) valoración teórico-documental, mediante la revisión y síntesis de seis documentos oficiales de RISS publicados entre 2012 y 2017, y 2) valoración práctica con los equipos de coordinación de cinco redes, dos descentralizadas y tres mixtas, usando la Herramienta de Valoración de RISS de la Organización Panamericana de la Salud. Resultados. La valoración teórica global alcanzó 55 puntos de desarrollo comparada con la valoración práctica de las cinco redes, que alcanzó 42,8. Según el análisis por ámbitos, el Modelo asistencial obtuvo mejores resultados en ambas valoraciones, mayor en la valoración teórica (62,5). Gobernanza y estrategia fue el ámbito que recibió la valoración más baja (41,7). Entre la valoración teórica y la práctica las diferencias en el análisis de ámbitos y de atributos fueron estadísticamente significativas (p = 0,007 y p < 0,001, respectivamente). Las redes con gestión descentralizada alcanzaron mejores valoraciones que las mixtas (p = 0,017). Conclusiones. Existe una brecha entre la valoración teórica y la práctica que sugiere que la aplicación de las herramientas y las estrategias definidas en los documentos son incompletas. El componente provisional sigue siendo el que genera mayor interés e importancia. En las redes mixtas se observó mayor dificultad de integración, probablemente debido a la doble gobernanza. Es necesario seguir evaluando las RISS.
[ABSTRACT]. Objective. There have been few evaluations of integrated health service delivery networks (IHSDN) in the Region of the Americas. Honduras has made progress in the implementation of tools and strategies based on the essential attributes of IHSDNs. The objective of this study is to assess and compare the development of IHSDNs in theoretical and practical terms, by type of management, in five networks in Honduras. Methods. The study was conducted in two stages: 1) a theoretical assessment based on a review and summary of six official documents on IHSDNs published between 2012 and 2017, and 2) a practical assessment in conjunction with the coordination teams of five networks, two of them with decentralized management and three of them with mixed management, using the IHSDN Assessment Tool of the Pan American Health Organization. Results. The overall theoretical assessment yielded a development score of (55 points), compared with the 42.8 of the practical assessment of the five networks. In the analysis by area, the model of care had better results in both assessments, with higher scores in the theoretical assessment (62.5). The area with the lowest score (41.7) was governance and strategy. The differences between the theoretical and practical assessment in the area and attribute analyses were statistically significant (p = 0.007 and p < 0.001, respectively). The networks with decentralized management had higher scores than those with mixed management (p = 0.017). Conclusions. There is a gap between the theoretical and practical assessment that suggests that application of the tools and strategies defined in the documents is incomplete. The provisional component remains the one that elicits the most interest and is considered the most important. Greater difficulties with integration were observed in the networks with mixed management, probably because of their dual governance. Continued evaluation of IHSDNs is necessary.
[RESUMO]. Objetivo. As redes integradas de serviços de saúde (RISS) têm sido pouco avaliadas na Região das Américas. Honduras fez avanços com a implementação de ferramentas e estratégias baseadas nos componentes básicos das RISS. O objetivo do presente estudo foi avaliar e comparar o desenvolvimento das RISS segundo o planejamento teórico-documental e a aplicação prática, por tipo de gestão, em cinco redes de Honduras. Métodos. O estudo foi realizado em duas etapas. Na primeira etapa foi feita uma avaliação teórico-documental, com a revisão e o resumo de seis documentos oficiais das RISS publicados entre 2012 e 2017. E, na segunda etapa, foi feita uma avaliação prática com as equipes de coordenação de cinco redes (duas descentralizadas e três mistas) com o uso da ferramenta de avaliação das RISS da Organização Pan-Americana da Saúde (OPAS). Resultados. A avaliação teórica atingiu 55 pontos de desenvolvimento geral comparados a 42,8 na avaliação prática das cinco redes. A análise por âmbitos demonstrou que o modelo assistencial obteve melhores resultados em ambas as avaliações, com uma pontuação maior na avaliação teórica (62,5). Governança e estratégia foi o âmbito que teve a menor pontuação (41,7). Entre as avaliações teórica e prática, as diferenças na análise dos âmbitos e atributos foram estatisticamente significativas (p = 0,007 e p < 0,001, respectivamente). As redes com gestão descentralizada comparada à mista obtiveram uma pontuação maior nas avaliações (p = 0,017). Conclusões. Existe uma defasagem entre a avaliação teórica e a prática que aponta para a aplicação incompleta das ferramentas e estratégias definidas nos documentos. O componente de prestação de serviços continua sendo o de maior interesse e importância. Observou-se uma maior dificuldade de integração nas redes mistas, possivelmente devido à dupla governança. É preciso continuar avaliando as RISS.
Assuntos
Serviços de Saúde , Política , Honduras , Serviços de Saúde , Reforma dos Serviços de Saúde , Política , Reforma dos Serviços de Saúde , Serviços de Saúde , Reforma dos Serviços de Saúde , PolíticaRESUMO
Inflammation supports the progression of alcohol-related organ injury. Recent research findings have linked ethanol exposure to changes in histone acetylation and deacetylation in the brain and in peripheral tissues, leading to ethanol-dependence related damage. One of the mechanisms that has been shown to play a major role during inflammation is the cannabinoid system. Previous research has demonstrated that ethanol can modulate cannabinoid receptors' functions. Our lab has shown that the G protein-coupled receptor (GPR55), a novel cannabinoid receptor, is upregulated in binge drinkers and in cells treated acutely with ethanol. Additionally, our group has also uncovered that chronic ethanol exposure leads to an increase in histone modifications, such as acetylation. However, the regulatory mechanism of GPR55 within the immune system under the influence of ethanol is poorly understood. Since changes in histone modifications might lead to changes in gene expression, we hypothesize that the mechanism of ethanol-induced upregulation of GPR55 is linked to epigenetic changes on histone proteins. Taking into account previous findings from our lab, the goal of the present study was to determine whether there is any relevant association between histone hyperacetylation and the regulation of the novel cannabinoid receptor GPR55 in monocyte-derived dendritic cells (MDDCs) of human origin treated acutely with ethanol. Therefore, monocytes were isolated from buffy coats and allowed to differentiate into MDDCs. The cells were treated with ethanol for 24 h, harvested, fixed, and stained with antibodies against GPR55. As expected, based on previous findings, confocal microscopy showed that ethanol exposure increases GPR55 expression. In order to demonstrate the correlation between histone acetylation and GPR55 expression regulation, the cells were treated with ethanol, harvested, and then the chromatin was extracted and fractionated for chromatin immunoprecipitation (ChIP) assay, followed by real-time qPCR for the analysis of DNA fragments. The results showed an enrichment of the histone modification H4K12ac in the GPR55 gene of MDDCs treated with ethanol. Furthermore, siRNA against the histone acetyltransferase Tip60 (responsible for the acetylation of H4K12) resulted in a downregulation of GPR55. In conjunction, these results indicate that in the presence of ethanol, the upregulation of GPR55 expression is accompanied by H4K12 acetylation, which might have a significant effect in the ability of this innate immune system's cells to cope with cellular stress induced by ethanol. However, the causality of ethanol regulation of H4K12ac in GPR55 expression changes still lacks further elucidation; therefore, additional experimental approaches to confirm a significant causality between H4K12 acetylation and ethanol regulation of GPR55 are currently undergoing in our lab.
Assuntos
Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Etanol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Histonas/efeitos dos fármacos , Histonas/metabolismo , Monócitos/citologia , Receptores Acoplados a Proteínas G/biossíntese , Acetilação/efeitos dos fármacos , Células Dendríticas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Histonas/química , Humanos , Lisina Acetiltransferase 5/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Receptores de Canabinoides , Regulação para Cima/efeitos dos fármacosRESUMO
This article aims to evaluate the evidence relating to the effectiveness of alcohol-based gel for hand sanitising, or 'handrub', in infection control in healthcare settings with particular reference to renal nursing, as this has become pertinent due to the increasing reliance on evidence-based practice. There is a need to implement better infection control strategies and education, to reinforce knowledge among the public, health professionals and those at high risk of infection not only in renal nursing, but also in other areas of practice. Healthcare-associated infections (HCAIs) put patients' safety at risk, increase morbidity and mortality, extend the length of hospital admission and increase the cost to the NHS. There is evidence that the prevalence of HCAIs in England can be minimised through the use of different infection control measures. For example, alcohol-based handrub has been found to be associated with minimising the spread of gastrointestinal infections not only in hospital settings, but also in childcare centres. In addition, the UK national guidelines recommend regular handwashing (implementing the right technique) when hands are visibly dirty and hand disinfection with alcohol-based handrub when they are not visibly dirty. This should be before, in between and after different healthcare activities are performed.
Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Desinfecção das Mãos/métodos , Higienizadores de Mão/uso terapêutico , Controle de Infecções/métodos , Enfermagem em Nefrologia/educação , Anti-Infecciosos Locais/uso terapêutico , Infecção Hospitalar/enfermagem , Inglaterra , Etanol/uso terapêutico , Prática Clínica Baseada em Evidências , Hospitais , Humanos , Guias de Prática Clínica como Assunto , Prevalência , Sabões/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: There have been few evaluations of integrated health service delivery networks (IHSDN) in the Region of the Americas. Honduras has made progress in the implementation of tools and strategies based on the essential attributes of IHSDNs. The objective of this study is to assess and compare the development of IHSDNs in theoretical and practical terms, by type of management, in five networks in Honduras. METHODS: The study was conducted in two stages: 1) a theoretical assessment based on a review and summary of six official documents on IHSDNs published between 2012 and 2017, and 2) a practical assessment in conjunction with the coordination teams of five networks, two of them with decentralized management and three of them with mixed management, using the IHSDN Assessment Tool of the Pan American Health Organization. RESULTS: The overall theoretical assessment yielded a development score of (55 points), compared with the 42.8 of the practical assessment of the five networks. In the analysis by area, the model of care had better results in both assessments, with higher scores in the theoretical assessment (62.5). The area with the lowest score (41.7) was governance and strategy. The differences between the theoretical and practical assessment in the area and attribute analyses were statistically significant (p = 0.007 and p < 0.001, respectively). The networks with decentralized management had higher scores than those with mixed management (p = 0.017). CONCLUSIONS: There is a gap between the theoretical and practical assessment that suggests that application of the tools and strategies defined in the documents is incomplete. The provisional component remains the one that elicits the most interest and is considered the most important. Greater difficulties with integration were observed in the networks with mixed management, probably because of their dual governance. Continued evaluation of IHSDNs is necessary.
OBJETIVO: As redes integradas de serviços de saúde (RISS) têm sido pouco avaliadas na Região das Américas. Honduras fez avanços com a implementação de ferramentas e estratégias baseadas nos componentes básicos das RISS. O objetivo do presente estudo foi avaliar e comparar o desenvolvimento das RISS segundo o planejamento teórico-documental e a aplicação prática, por tipo de gestão, em cinco redes de Honduras. MÉTODOS: O estudo foi realizado em duas etapas. Na primeira etapa foi feita uma avaliação teórico-documental, com a revisão e o resumo de seis documentos oficiais das RISS publicados entre 2012 e 2017. E, na segunda etapa, foi feita uma avaliação prática com as equipes de coordenação de cinco redes (duas descentralizadas e três mistas) com o uso da ferramenta de avaliação das RISS da Organização Pan-Americana da Saúde (OPAS). RESULTADOS: A avaliação teórica atingiu 55 pontos de desenvolvimento geral comparados a 42,8 na avaliação prática das cinco redes. A análise por âmbitos demonstrou que o modelo assistencial obteve melhores resultados em ambas as avaliações, com uma pontuação maior na avaliação teórica (62,5). Governança e estratégia foi o âmbito que teve a menor pontuação (41,7). Entre as avaliações teórica e prática, as diferenças na análise dos âmbitos e atributos foram estatisticamente significativas (p = 0,007 e p < 0,001, respectivamente). As redes com gestão descentralizada comparada à mista obtiveram uma pontuação maior nas avaliações (p = 0,017). CONCLUSÕES: Existe uma defasagem entre a avaliação teórica e a prática que aponta para a aplicação incompleta das ferramentas e estratégias definidas nos documentos. O componente de prestação de serviços continua sendo o de maior interesse e importância. Observou-se uma maior dificuldade de integração nas redes mistas, possivelmente devido à dupla governança. É preciso continuar avaliando as RISS.
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OBJECTIVE: The objective of this study was to understand whether histone deacetylase (HDACs) inhibitor Trichostatin A or TSA can block and/or reverse chronic alcohol exposure-induced ROS in human monocyte-derived dendritic cells (MDDCs). Additionally, since nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a known regulator of antioxidant responses, we studied the effects of alcohol and TSA on ROS production and modulation of Nrf2 by MDDCs. METHODS: Intra-cellular, extra-cellular, and total ROS levels were measured in MDDCs treated chronically with alcohol (0.1 and 0.2 % EtOH) using 2',7'-dichlorofluorescin diacetate (DCF-DA) followed by detection of ROS in microplate reader and imaging flow cytometer. Nrf2 expression was analyzed by qRT- PCR and western blot. In addition, NFE2L2 (Nrf2), class I HDAC genes HDAC1, HDAC2, and histone acetyltransferase genes KAT5 were analyzed in silico using the GeneMania prediction server. RESULTS: Our results confirmed alcohol's ability to increase intracellular ROS levels in MDDCs within minutes of treatment. Our findings have also demonstrated, for the first time, that TSA has a transient protective effect on MDDCs treated chronically with alcohol since the ability of TSA to reduce intracellular ROS levels is only detected up to 15 minutes post-chronic alcohol treatment with no significant protective effects by 10 hours. In addition, chronic alcohol treatment was able to increase the expression of the antioxidant regulator Nrf2 in a dose dependent manner, and the effect of the higher amount of alcohol (0.2%) on Nrf2 gene expression was significantly enhanced by TSA. CONCLUSION: This study demonstrates that TSA has a transient protective effect against ROS induced by chronic alcohol exposure of human MDDCs and chronic long-term exposure of MDDCs with alcohol and TSA induces cellular toxicity. It also highlights imaging flow cytometry as a novel tool to detect intracellular ROS levels. Overall, the effect of TSA might be mediated through Nrf2; however, further studies are needed to fully understand the molecular mechanisms.
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RESUMEN Objetivo En la Región de las Américas se han realizado pocas evaluaciones de redes integradas de servicios de salud (RISS). Honduras ha avanzado en la implementación de herramientas y estrategias basadas en los atributos esenciales de las RISS. Este estudio tiene como objetivo valorar y comparar el desarrollo de RISS en su planteamiento teórico-documental y en su aplicación práctica, por tipo de gestión, en cinco redes de Honduras. Métodos El estudio se realizó en dos etapas: 1) valoración teórico-documental, mediante la revisión y síntesis de seis documentos oficiales de RISS publicados entre 2012 y 2017, y 2) valoración práctica con los equipos de coordinación de cinco redes, dos descentralizadas y tres mixtas, usando la Herramienta de Valoración de RISS de la Organización Panamericana de la Salud. Resultados La valoración teórica global alcanzó 55 puntos de desarrollo comparada con la valoración práctica de las cinco redes, que alcanzó 42,8. Según el análisis por ámbitos, el Modelo asistencial obtuvo mejores resultados en ambas valoraciones, mayor en la valoración teórica (62,5). Gobernanza y estrategia fue el ámbito que recibió la valoración más baja (41,7). Entre la valoración teórica y la práctica las diferencias en el análisis de ámbitos y de atributos fueron estadísticamente significativas (p = 0,007 y p < 0,001, respectivamente). Las redes con gestión descentralizada alcanzaron mejores valoraciones que las mixtas (p = 0,017). Conclusiones Existe una brecha entre la valoración teórica y la práctica que sugiere que la aplicación de las herramientas y las estrategias definidas en los documentos son incompletas. El componente provisional sigue siendo el que genera mayor interés e importancia. En las redes mixtas se observó mayor dificultad de integración, probablemente debido a la doble gobernanza. Es necesario seguir evaluando las RISS.
ABSTRACT Objective There have been few evaluations of integrated health service delivery networks (IHSDN) in the Region of the Americas. Honduras has made progress in the implementation of tools and strategies based on the essential attributes of IHSDNs. The objective of this study is to assess and compare the development of IHSDNs in theoretical and practical terms, by type of management, in five networks in Honduras. Methods The study was conducted in two stages: 1) a theoretical assessment based on a review and summary of six official documents on IHSDNs published between 2012 and 2017, and 2) a practical assessment in conjunction with the coordination teams of five networks, two of them with decentralized management and three of them with mixed management, using the IHSDN Assessment Tool of the Pan American Health Organization. Results The overall theoretical assessment yielded a development score of (55 points), compared with the 42.8 of the practical assessment of the five networks. In the analysis by area, the model of care had better results in both assessments, with higher scores in the theoretical assessment (62.5). The area with the lowest score (41.7) was governance and strategy. The differences between the theoretical and practical assessment in the area and attribute analyses were statistically significant (p = 0.007 and p < 0.001, respectively). The networks with decentralized management had higher scores than those with mixed management (p = 0.017). Conclusions There is a gap between the theoretical and practical assessment that suggests that application of the tools and strategies defined in the documents is incomplete. The provisional component remains the one that elicits the most interest and is considered the most important. Greater difficulties with integration were observed in the networks with mixed management, probably because of their dual governance. Continued evaluation of IHSDNs is necessary.
RESUMO Objetivo As redes integradas de serviços de saúde (RISS) têm sido pouco avaliadas na Região das Américas. Honduras fez avanços com a implementação de ferramentas e estratégias baseadas nos componentes básicos das RISS. O objetivo do presente estudo foi avaliar e comparar o desenvolvimento das RISS segundo o planejamento teórico-documental e a aplicação prática, por tipo de gestão, em cinco redes de Honduras. Métodos O estudo foi realizado em duas etapas. Na primeira etapa foi feita uma avaliação teórico-documental, com a revisão e o resumo de seis documentos oficiais das RISS publicados entre 2012 e 2017. E, na segunda etapa, foi feita uma avaliação prática com as equipes de coordenação de cinco redes (duas descentralizadas e três mistas) com o uso da ferramenta de avaliação das RISS da Organização Pan-Americana da Saúde (OPAS). Resultados A avaliação teórica atingiu 55 pontos de desenvolvimento geral comparados a 42,8 na avaliação prática das cinco redes. A análise por âmbitos demonstrou que o modelo assistencial obteve melhores resultados em ambas as avaliações, com uma pontuação maior na avaliação teórica (62,5). Governança e estratégia foi o âmbito que teve a menor pontuação (41,7). Entre as avaliações teórica e prática, as diferenças na análise dos âmbitos e atributos foram estatisticamente significativas (p = 0,007 e p < 0,001, respectivamente). As redes com gestão descentralizada comparada à mista obtiveram uma pontuação maior nas avaliações (p = 0,017). Conclusões Existe uma defasagem entre a avaliação teórica e a prática que aponta para a aplicação incompleta das ferramentas e estratégias definidas nos documentos. O componente de prestação de serviços continua sendo o de maior interesse e importância. Observou-se uma maior dificuldade de integração nas redes mistas, possivelmente devido à dupla governança. É preciso continuar avaliando as RISS.
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Política , Reforma dos Serviços de Saúde , Serviços de Saúde , HondurasRESUMO
BACKGROUND: G. intestinalis and Cryptosporidium spp. are responsible for gastrointestinal infections worldwide. Contaminated food, feces, drinking water and predictors such as poverty, cultural and behavioral aspects have been involved in their transmission. Published studies about these infections are limited in Mexico. Cananea, Sonora is located in northwest Mexico and is one of the regions with the lowest marginalization index in the Sonora state. However, its rate of gastrointestinal infections increased from 48.7/1000 in 2003 to 77.9/1000 in 2010 in the general population. It was estimated that the prevalence of giardiasis can range from 20 to 30% in the Sonoran childhood population. However, the prevalence of giardiasis and cryptosporidiosis are unknown in Cananea, Sonora and they are likely contributing to its gastrointestinal infections rates. METHODS: A total of 173 children (average age 8.8 ± 2.8 years) participated in this cross-sectional study. Anthropometric measurements and stool analysis were performed. Socioeconomic, cultural and symptomatology information were collected. The association between the risk factors and intestinal parasitic infections was analyzed by multivariate analysis using the STATA/SE package at a significance level of p ≤ 0.05. RESULTS: More than half of the children (n = 103, 60%) had intestinal parasitic infections. Cryptosporidium spp. showed the highest prevalence (n = 47, 27%), which was followed by G. intestinalis (n = 40, 23%). Children with giardiasis and cryptosporidiosis had lower H/A and BMI/A Z scores than children who were free of these infections. Children with giardiasis were at higher risk (OR = 4.0; 95%CI = 1.11-13.02; p = 0.030) of reporting abdominal pain, and children who drank tap water were at higher risk (OR = 5.0; 95% CI = 1.41-17.20; p = 0.012) of cryptosporidiosis. CONCLUSIONS: This was the first epidemiological study conducted in children in the region of Cananea, Sonora in northwest Mexico. The findings revealed a high prevalence of cryptosporidiosis and giardiasis, and their interactions with multiple risk factors were investigated. This study suggested that giardiasis and cryptosporidiosis may play an important role as causative factors of gastrointestinal diseases in the study region. Regional authorities must analyze water for human consumption to search for Cryptosporidium spp. and G. intestinalis.
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Criptosporidiose/epidemiologia , Giardíase/epidemiologia , Criança , Estudos Transversais , Cryptosporidium/isolamento & purificação , Fezes/parasitologia , Feminino , Giardia/isolamento & purificação , Humanos , Masculino , México/epidemiologia , Prevalência , Fatores de RiscoRESUMO
A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
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Previous reports on epigenetic mechanisms involved in alcohol abuse have focus on hepatic and neuronal regions, leaving the immune system and specifically monocyte-derived dendritic cells (MDDCs) understudied. Our lab has previously shown histone deacetylases are modulated in cells derived from alcohol users and after in vitro acute alcohol treatment of human MDDCs. In the current study, we developed a novel screening tool using matrix assisted laser desorption ionization-fourier transform-ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS) and single cell imaging flow cytometry to detect post-translational modifications (PTMs) in human MDDCs due to chronic alcohol exposure. Our results demonstrate, for the first time, in vitro chronic alcohol exposure of MDDCs modulates H3 and H4 and induces a significant increase in acetylation at H4K12 (H4K12ac). Moreover, the Tip60/HAT inhibitor, NU9056, was able to block EtOH-induced H4K12ac, enhancing the effect of EtOH on IL-15, RANTES, TGF-ß1, and TNF-α cytokines while restoring MCP-2 levels, suggesting that H4K12ac may be playing a major role during inflammation and may serve as an inflammation regulator or a cellular stress response mechanism under chronic alcohol conditions.
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Alcoolismo/patologia , Células Dendríticas/química , Células Dendríticas/efeitos dos fármacos , Processamento de Proteína Pós-Traducional , Proteoma/análise , Células Cultivadas , Citometria de Fluxo , Histonas/metabolismo , Humanos , Análise de Célula Única , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Dendritic cells (DCs) are antigen presenting cells of the immune system that play a crucial role in lymphocyte responses, host defense mechanisms, and pathogenesis of inflammation. Isolation and study of DCs have been important in biological research because of their distinctive features. Although they are essential key mediators of the immune system, DCs are very rare in blood, accounting for approximately 0.1 - 1% of total blood mononuclear cells. Therefore, alternatives for isolation methods rely on the differentiation of DCs from monocytes isolated from peripheral blood mononuclear cells (PBMCs). The utilization of proper isolation techniques that combine simplicity, affordability, high purity, and high yield of cells is imperative to consider. In the current study, two distinct methods for the generation of DCs will be compared. Monocytes were selected by adherence or negatively enriched using magnetic separation procedure followed by differentiation into DCs with IL-4 and GM-CSF. Monocyte and MDDC viability, proliferation, and phenotype were assessed using viability dyes, MTT assay, and CD11c/ CD14 surface marker analysis by imaging flow cytometry. Although the magnetic separation method yielded a significant higher percentage of monocytes with higher proliferative capacity when compared to the adhesion method, the findings have demonstrated the ability of both techniques to simultaneously generate monocytes that are capable of proliferating and differentiating into viable CD11c+ MDDCs after seven days in culture. Both methods yielded > 70% CD11c+ MDDCs. Therefore, our results provide insights that contribute to the development of reliable methods for isolation and characterization of human DCs.
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Células Dendríticas , Citometria de Fluxo , Leucócitos Mononucleares , Diferenciação Celular , Separação Celular , Células Cultivadas , Humanos , MonócitosRESUMO
Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prove to be valuable therapeutic targets. However, the involvement of histone deacetylases (HDACs) on alcohol-induced oxidative stress of human primary monocyte-derived dendritic cells (MDDCs) has not been elucidated. In the current study, we took a novel approach combining ex vivo, in vitro and in silico analyses to elucidate the mechanisms of alcohol-induced oxidative stress and role of HDACs in the periphery. ex vivo and in vitro analyses of alcohol-modulation of class I HDACs and activity by MDDCs from self-reported alcohol users and non-alcohol users was performed. Additionally, MDDCs treated with alcohol were assessed using qRT-PCR, western blot, and fluorometric assay. The functional effects of alcohol-induce oxidative stress were measured in vitro using PCR array and in silico using gene expression network analysis. Our findings show, for the first time, that MDDCs from self-reported alcohol users have higher levels of class I HDACs compare to controls and alcohol treatment in vitro differentially modulates HDACs expression. Further, HDAC inhibitors (HDACi) blocked alcohol-induction of class I HDACs and modulated alcohol-induced oxidative stress related genes expressed by MDDCs. In silico analysis revealed new target genes and pathways on the mode of action of alcohol and HDACi. Findings elucidating the ability of alcohol to modulate class I HDACs may be useful for the treatment of alcohol-induced oxidative damage and may delineate new potential immune-modulatory mechanisms.
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Consumo de Bebidas Alcoólicas , Benzamidas/farmacologia , Células Dendríticas/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Estresse Oxidativo , Pirimidinas/farmacologia , Antioxidantes/metabolismo , Células Dendríticas/enzimologia , Feminino , Humanos , Técnicas In Vitro , Masculino , Espécies Reativas de Oxigênio/metabolismoRESUMO
Due to the legalization of marijuana and the increased demand for cannabis and alcohol consumption, research efforts highlighting the biomedical consequences of the use of alcohol and cannabinoids are not only relevant to the substance abuse scientific field, but are also of public health interest. Moreover, an overview of the recent literature about alcohol and cannabinoids neuro-immunomodulatory effects highlighting their future therapeutic potentials will provide a significant contribution to science and medicine. Therefore, in the current review, we will first discuss briefly the prevalence of alcohol and marijuana abuse, followed by a discussion on the individual effects of alcohol and cannabinoids on the immune system; then, we will focus on the role of endocannabinoids on the alcohol-induced inflammatory effects. In addition, the review also incorporates cytokine array data obtained from human monocyte-derived dendritic cells, providing a different perspective on the alcohol and cannabinoid abuse divergent effects on cytokine production. The final section will highlight the therapeutic potential of cannabinoid receptors and the novel strategies to treat alcohol dependence as determined by in vitro, in vivo and clinical studies.