RESUMEN
Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.
Asunto(s)
Infecciones por Escherichia coli , Escherichia coli , Pulmón , Polisacáridos Bacterianos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Animales , Femenino , Masculino , Ratones , Biopelículas , Escherichia coli/fisiología , Hipotermia/metabolismo , Hipotermia/patología , Inflamación/metabolismo , Inflamación/patología , Pulmón/microbiología , Pulmón/patología , Neumonía/microbiología , Neumonía/patología , Pseudomonas aeruginosa/fisiología , Células Receptoras Sensoriales , Polisacáridos Bacterianos/metabolismo , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/patología , Infecciones por Pseudomonas/metabolismo , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/patología , Nociceptores/metabolismoRESUMEN
Purpose of the study: Macrolide therapy is effective in reducing chronic obstructive pulmonary disease (COPD) exacerbations. Our recent study has shown the effectiveness of taking azithromycin in COPD patients, not only ex-smokers but also current smokers. Beyond their anti-microbial effects, macrolides have anti-inflammatory and immunomodulatory properties. The aim of this study was to determine if pretreatment with azithromycin modulates cigarette smoke-induced inflammation in airway epithelial cells. We hypothesized that pretreatment with azithromycin decreases exacerbation frequency by modulating inflammation in human airway epithelial cells exposed to cigarette smoke. Materials and methods: BEAS-2B bronchial epithelial cells were incubated with 5% cigarette smoke extract (CSE) for 3 h, 6 h, and 24 h. Then, airway epithelial cells were pretreated with azithromycin and exposed to 5% CSE. In each stage, the expression and release of IL-6 and IL-8 mRNA were analyzed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: There was a significant increase of IL-6 and IL-8 mRNA, as well as an increase in extracellular IL-8 protein following exposure to 5% CSE. When cells were pretreated with azithromycin and exposed to 5% CSE for 3 h, there was a significant dose-dependent decrease in the expression of IL-6 mRNA. A final concentration of 9 µg/mL of azithromycin was sufficient to decrease IL-6, IL-8 mRNA, and extracellular IL-8 levels. Conclusion: Pretreatment with azithromycin decreased the expression of IL-6 and IL-8 mRNA and the release of IL-8 in bronchial epithelial cells exposed to cigarette smoke. These results demonstrate the direct effect of azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.
Asunto(s)
Azitromicina , Enfermedad Pulmonar Obstructiva Crónica , Azitromicina/farmacología , Bronquios , Células Epiteliales , Humanos , Mediadores de Inflamación , Humo/efectos adversos , FumarRESUMEN
The objective of this study is to evaluate whether a chronic obstructive pulmonary disease (COPD) self-management education program with coaching of a case manager improves patient-related outcomes and leads to practice changes in primary care. COPD patients from six family medicine clinics (FMCs) participated in a 1-year educational program offered by trained case managers who focused on treatment adherence, inhaler techniques, smoking cessation, and the use of an action plan for exacerbations. Health-care utilization, health-related quality of life (HRQL), treatment adherence, inhaler technique, and COPD knowledge were assessed at each visit with validated questionnaires. We also evaluated whether the use of spirometry and the assessment of individual patient needs led to a more COPD-targeted treatment by primary care physicians, based on changes in prescriptions for COPD (medication, immunization, and written action plan). Fifty-four patients completed the follow-up visits and were included in the analysis. The number of unscheduled physician visits went from 40 the year before intervention to 17 after 1 year of educational intervention ( p = 0.033). Emergency room visits went from five to two and hospitalizations from two to three (NS). Significant improvements were observed in HRQL ( p = 0.0001), treatment adherence ( p = 0.025), adequate inhaler technique ( p < 0.0001), and COPD knowledge ( p < 0.001). Primary care physicians increased their prescriptions for long-acting bronchodilators with/without inhaled corticosteroid, flu immunizations, and COPD action plans in the event patient had an exacerbation. The COPD self-management educational intervention in FMCs reduced unscheduled visits to the clinic and improved patients' quality of life, self-management skills, and knowledge. The program had a positive impact on COPD-related practices by primary care physicians in the FMCs.
Asunto(s)
Manejo de Caso , Conocimientos, Actitudes y Práctica en Salud , Hospitalización/estadística & datos numéricos , Cumplimiento de la Medicación/estadística & datos numéricos , Educación del Paciente como Asunto/métodos , Atención Primaria de Salud , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Autocuidado/métodos , Corticoesteroides/uso terapéutico , Anciano , Broncodilatadores/uso terapéutico , Servicio de Urgencia en Hospital/estadística & datos numéricos , Medicina Familiar y Comunitaria , Femenino , Estado de Salud , Humanos , Vacunas contra la Influenza/uso terapéutico , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Quebec , EspirometríaRESUMEN
Despite surviving a SARS-CoV-2 infection, some individuals experience an intense post-infectious Multisystem Inflammatory Syndrome (MIS) of uncertain etiology. Children with this syndrome (MIS-C) can experience a Kawasaki-like disease, but mechanisms in adults (MIS-A) are not clearly defined. Here we utilize a deep phenotyping approach to examine immunologic responses in an individual with MIS-A. Results are contextualized to healthy, convalescent, and acute COVID-19 patients. The findings reveal systemic inflammatory changes involving novel neutrophil and B-cell subsets, autoantibodies, complement, and hypercoagulability that are linked to systemic vascular dysfunction. This deep patient profiling generates new mechanistic insight into this rare clinical entity and provides potential insight into other post-infectious syndromes.
Asunto(s)
COVID-19 , Enfermedades del Tejido Conjuntivo , Niño , Humanos , Adulto , Neutrófilos , SARS-CoV-2RESUMEN
BACKGROUND: Individuals with COPD and preserved ratio impaired spirometry (PRISm) findings in clinical settings have an increased risk of cardiovascular disease (CVD). RESEARCH QUESTION: Do individuals with mild to moderate or worse COPD and PRISm findings in community settings have a higher prevalence and incidence of CVD compared with individuals with normal spirometry findings? Can CVD risk scores be improved when impaired spirometry is added? STUDY DESIGN AND METHODS: The analysis was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Prevalence of CVD (ischemic heart disease [IHD] and heart failure [HF]) and their incidence over 6.3 years were compared between groups with impaired and normal spirometry findings using logistic regression and Cox models, respectively, adjusting for covariables. Discrimination of the pooled cohort equations (PCE) and Framingham risk score (FRS) in predicting CVD were assessed with and without impaired spirometry. RESULTS: Participants (n = 1,561) included 726 people with normal spirometry findings and 835 people with impaired spirometry findings (COPD Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 disease, n = 408; GOLD stage ≥ 2, n = 331; PRISm findings, n = 96). Rates of undiagnosed COPD were 84% in GOLD stage 1 and 58% in GOLD stage ≥ 2 groups. Prevalence of CVD (IHD or HF) was significantly higher among individuals with impaired spirometry findings and COPD compared with those with normal spirometry findings, with ORs of 1.66 (95% CI, 1.13-2.43; P = .01∗) (∗ indicates statistical significane with P < .05) and 1.55 (95% CI, 1.04-2.31; P = .033∗), respectively. Prevalence of CVD was significantly higher in participants having PRISm findings and COPD GOLD stage ≥ 2, but not GOLD stage 1. CVD incidence was significantly higher, with hazard ratios of 2.07 (95% CI, 1.10-3.91; P = .024∗) for the impaired spirometry group and 2.09 (95% CI, 1.10-3.98; P = .024∗) for the COPD group compared to individuals with normal spirometry findings. The difference was significantly higher among individuals with COPD GOLD stage ≥ 2, but not GOLD stage 1. The discrimination for predicting CVD was low and limited when impaired spirometry findings were added to either risk score. INTERPRETATION: Individuals with impaired spirometry findings, especially those with moderate or worse COPD and PRISm findings, have increased comorbid CVD compared with their peers with normal spirometry findings, and having COPD increases the risk of CVD developing.
Asunto(s)
Enfermedades Cardiovasculares , Isquemia Miocárdica , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios de Cohortes , Enfermedades Cardiovasculares/epidemiología , Volumen Espiratorio Forzado , Canadá/epidemiología , Factores de Riesgo , EspirometríaRESUMEN
Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated genes and activated IL-1R2+ neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
Asunto(s)
COVID-19/inmunología , Citocinas/inmunología , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Neutrófilos/inmunología , Neumonía Bacteriana/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Adulto , Anciano , COVID-19/complicaciones , COVID-19/genética , Comunicación Celular , Cromatografía Liquida , Regulación hacia Abajo , Femenino , Redes Reguladoras de Genes , Humanos , Inmunidad Innata/inmunología , Interferones/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/genética , Prostaglandinas/inmunología , Proteómica , RNA-Seq , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/genética , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Análisis de la Célula Individual , Espectrometría de Masas en Tándem , Tratamiento Farmacológico de COVID-19RESUMEN
The lung naturally resists Aspergillus fumigatus (Af) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis-severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use-in human patients and murine models. We found a conserved and essential coupling of innate B1a lymphocytes, Af-binding natural immunoglobulin G antibodies, and lung neutrophils. Failure of this axis concealed Af from neutrophils, allowing rapid fungal invasion and disease. Reconstituting the axis with immunoglobulin therapy reestablished resistance, thus representing a realistic pathway to repurpose currently available therapies. Together, we report a vital host resistance pathway that is responsible for protecting against life-threatening aspergillosis in the context of distinct susceptibilities.
Asunto(s)
COVID-19 , Neutrófilos , Humanos , Animales , Ratones , SARS-CoV-2 , Esteroides/uso terapéuticoRESUMEN
While emerging data suggest nucleotide oligomerization domain receptor 1 (NOD1), a cytoplasmic pattern recognition receptor, may play an important and complementary role in the immune response to bacterial infection, its role in cancer metastasis is entirely unknown. Hence, we sought to determine the effects of NOD1 on metastasis. NOD1 expression in paired human primary colon cancer, human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting (WB). Clinical significance of NOD1 was assessed using TCGA survival data. A series of in vitro and in vivo functional assays, including adhesion, migration, and metastasis, was conducted to assess the effect of NOD1. C12-iE-DAP, a highly selective NOD1 ligand derived from gram-negative bacteria, was used to activate NOD1. ML130, a specific NOD1 inhibitor, was used to block C12-iE-DAP stimulation. Stable knockdown (KD) of NOD1 in human colon cancer cells (HT29) was constructed with shRNA lentiviral transduction and the functional assays were thus repeated. Lastly, the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors. Our data demonstrate that NOD1 is highly expressed in human colorectal cancer (CRC) and human and murine CRC cell lines. Clinically, we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC. Subsequently, we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion, migration and metastasis. These effects are predominantly mediated via the p38 mitogen activated protein kinase (MAPK) pathway. This is the first study implicating NOD1 in cancer metastasis, and thus identifying this receptor as a putative therapeutic target.
Asunto(s)
Adenocarcinoma/metabolismo , Neoplasias del Colon/metabolismo , Proteína Adaptadora de Señalización NOD1/fisiología , Adenocarcinoma/patología , Animales , Adhesión Celular , Línea Celular , Movimiento Celular , Neoplasias del Colon/patología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoAsunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/inmunología , Interleucinas/inmunología , Infiltración Neutrófila , Humanos , Interleucina-33 , Interleucinas/genética , Pseudomonas aeruginosa/inmunología , ARN Mensajero/metabolismo , Mucosa Respiratoria/inmunologíaRESUMEN
Introduction: Self-management interventions with Written Action Plans and case management support have been shown to improve outcomes in patients with chronic obstructive pulmonary disease (COPD). Novel telehealth technologies may improve self-management interventions. The objectives of this study were to determine whether the use of an interactive phone telesystem increases Action Plan adherence, improves exacerbation recovery and reduces healthcare use in a real-life practice of a COPD clinic. Methods: Initially, 40 patients were followed by a COPD telesystem for 1 year. Detailed data from patients' behaviours during exacerbations was recorded. The telesystem use was then extended to 256 patients from a real-life COPD clinic. Healthcare utilisation for the year before and after telesystem enrolment was then assessed through hospital administrative databases. Results: Thirty-three of the 40 patients completed the initial 1-year study. Eighty-one exacerbations were reported in the 1-year follow-up. Action Plan adherence was observed for 72% of the exacerbations and those who were adherent had a significantly faster exacerbation recovery time. The large-scale implementation of the telesystem resulted in a significant decrease in the proportion of patients with ≥1 respiratory-related emergency room (ER) visits (120 before vs 110 after enrolment, p<0.001) and with ≥1 COPD-related hospitalisations (75 before vs 65 after enrolment, p<0.001). Discussion: COPD Written Action Plan adherence was further enhanced with the use of telehealth technologies in a specialised clinic with experience in COPD self-management. Patients followed by the telesystem recovered faster from exacerbations and had a further decrease in COPD-related ER visits and hospitalisations. Trial registration number: NCT02275078.
Asunto(s)
Manejo de Caso , Cooperación del Paciente/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Automanejo/métodos , Telemedicina/métodos , Anciano , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Calidad de Vida , Automanejo/estadística & datos numéricos , Brote de los Síntomas , Teléfono , Resultado del TratamientoRESUMEN
Objetivo: descrever o acompanhamento do recém-nascido pré-termo na terceira etapa do método canguru na perspectiva de enfermeiras da Atenção Primária. Método: estudo qualitativo, descritivo e exploratório realizado nas unidades básicas de saúde do município do interior da Bahia, com nove enfermeiras. Utilizou-se a entrevista semi-estruturada e a análise de conteúdo de Bardin. Resultados: as enfermeiras compreendem o que é um prematuro superficialmente, porém não entendem exatamente como funciona o Método Canguru. Dentre as facilidades, destaca-se o auxílio dos Agentes Comunitários de Saúde e quanto às dificuldades a que mais prevaleceu foi a fragilidade na referência e contrarreferência. Considerações finais: em vista disso, evidencia-se a necessidade da educação permanente para as enfermeiras da Atenção Primária, da sistematização da terceira etapa do Método e da formação profissional para enfermagem no intuito de melhorar a informação a respeito do prematuro, de modo a disseminar conhecimento que favoreça o atendimento a esse público.
Objetivo: describir el acompañamiento del recién nacido pre-término en la tercera etapa del método canguro en la perspectiva de enfermeras de la Atención Primaria. Método: estudio cualitativo, descriptivo y exploratorio realizado en las unidades básicas de salud del municipio del interior de Bahía, con nueve enfermeras. Se utilizó la entrevista semi-estructurada y el análisis de contenido de Bardin. Resultados: las enfermeras comprenden lo que es un prematuro superficialmente, pero no entienden exactamente cómo funciona el Método Canguro. Entre las facilidades, se destaca la ayuda de los Agentes Comunitarios de Salud y en cuanto a las dificultades que más prevaleció fue la fragilidad en la referencia y contrarreferencia. Consideraciones finales: en vista de ello, se evidencia la necesidad de la educación permanente para las enfermeras de la Atención Primaria, de la sistematización de la tercera etapa del Método y de la formación profesional para enfermería con el fin de mejorar la información acerca del prematuro, de modo a diseminar conocimiento que favorezca la atención a ese público.
Objective: to describe the follow-up of the preterm newborn in the third stage of the kangaroo method from the perspective of Primary Care nurses. Method: a qualitative, descriptive and exploratory study conducted in the basic health units of the city in the interior of Bahia, with nine nurses. The semi-structured interview and content analysis of Bardin were used. Results: nurses understand what a premature infant is superficially, but do not understand exactly how the Kangaroo Method works. Among the facilities, the help of Community Health Agents stand out, and the difficulties that prevailed most were the fragility in the reference and counter-reference. Final considerations: in view of this, it is evident the need for continuing education for nurses in Primary Care, the systematization of the third stage of the Method and professional training for nursing in order to improve information about the premature child, to disseminate knowledge that favors the service to this public.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Atención Primaria de Salud/métodos , Recien Nacido Prematuro/crecimiento & desarrollo , Cuidado del Niño , Investigación CualitativaRESUMEN
As the addition of low concentrations of oxygen can favor the initial degradation of benzene, toluene, ethylbenzene, and xylenes (BTEX) compounds, this work verified the applicability of the microaerobic technology to enhance BTEX removal in an anaerobic bioreactor supplemented with high and low co-substrate (ethanol) concentrations. Additionally, structural alterations on the bioreactor microbiota were assessed throughout the experiment. The bioreactor was fed with a synthetic BTEX-contaminated water (~ 3 mg L-1 of each compound) and operated at a hydraulic retention time of 48 h. The addition of low concentrations of oxygen (1.0 mL min-1 of atmospheric air at 27 °C and 1 atm) assured high removal efficiencies (> 80%) for all compounds under microaerobic conditions. In fact, the applicability of this technology showed to be viable to enhance BTEX removal from contaminated waters, especially concerning benzene (with a 30% removal increase), which is a very recalcitrant compound under anaerobic conditions. However, high concentrations of ethanol adversely affected BTEX removal, especially benzene, under anaerobic and microaerobic conditions. Finally, although bacterial community richness decreased at low concentrations of ethanol, in general, the bioreactor microbiota could deal with the different operational conditions and preserved its functionality during the whole experiment.
Asunto(s)
Reactores Biológicos/microbiología , Hidrocarburos Aromáticos/metabolismo , Contaminantes del Agua/metabolismo , Purificación del Agua/métodos , AerobiosisRESUMEN
Body image, according to the definition by Ledoux et al.(1) is "the systematic, cognitive, affective, conscious, and unconscious representation that people have concerning their bodies during their biological development and throughout their social relationships". OBJECTIVE: To determine the prevalence of body image satisfaction (BIS) and its relationship with sociodemographic, functional and clinical aspects in older adults. METHODS: A cross-sectional, analytical and prospective study of a random sample of older adults from all health districts of Porto Alegre (30 health units) was conducted. The following aspects were studied: sociodemographic data (sex, age, marital status and education), BIS (Stunkard's scale), functional tests (30 seconds Sit/Stand Test, time to walk 10m, Handgrip Strength - HGS), physical activity (Minnesota Questionnaire) and cognition (Mini-Mental State Examination). RESULTS: Most of the 532 participants were dissatisfied with their body image (92.5%), particularly the women (71.7%). After Binary Logistic Regression (6 steps), BIS predictors were: high scores for the Sit/Stand (OR: 1.13; p=0.013), higher HGS (OR: 1.06; p=0.049), shorter time engaged in physical activity (OR: 0.77; p<0.001). CONCLUSION: The prevalence of BIS was low and most of the variables analyzed bore no relation to BIS. Notwithstanding, a relationship was found with greater HGS, higher Sit/Stand score and less time engaged in physical activity. Given the scarcity of studies on this subject, our study furthers the knowledge on how body image affects this population group.
A imagem corporal, de acordo com a definição de Ledoux et al.(1), é "a representação sistemática, cognitiva, afetiva, consciente e inconsciente que as pessoas possuem em relação ao seu corpo durante o seu desenvolvimento biológico e ao longo de suas relações sociais". OBJETIVO: Determinar a prevalência de satisfação com a imagem corporal (BIS) e sua relação com aspectos sociodemográficos, funcionais e clínicos em idosos. MÉTODOS: Estudo transversal, analítico e prospectivo, realizado em uma amostra aleatória de idosos de todos os distritos sanitários de Porto Alegre (30 unidades de saúde). Os seguintes aspectos foram estudados: dados sociodemográficos (sexo, idade, estado civil e escolaridade), BIS (escala de Stunkard), testes funcionais (30 segundos Sit/Stand Test, tempo de caminhada 10m, Handgrip Strength - HGS) atividade física (Minnesota Questionnaire) e cognição (Mini Mental State Examination). RESULTADOS: A maioria dos 532 participantes estava insatisfeita com a imagem corporal (92,5%), particularmente as mulheres (71,7%). Após a Regressão Logística Binária (6 passos), os preditores do BIS foram: escores altos para o sentar/levantar (OR: 1,13; p=0,013), maior FP (OR: 1,06; p=0,049), menor tempo gasto em atividade física (OR: 0,77; p<0,001). CONCLUSÃO: A prevalência do BIS foi baixa e a maioria das variáveis ââanalisadas não apresentou relação com o BIS. Não obstante, foi encontrada uma relação com maior FPP, maior escore de Sit/Stand e menor tempo gasto em atividade física. Devido à escassez de estudos sobre o assunto, nossa pesquisa ajuda a aumentar o conhecimento sobre como a imagem corporal afeta essa parcela da população.
RESUMEN
Chromosomal region 17q12-q21 is associated with asthma and harbors regulatory polymorphisms that influence expression levels of all five protein-coding genes in the region: IKAROS family zinc finger 3 (Aiolos) (IKZF3), zona pellucida binding protein 2 (ZPBP2), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and gasdermins A and B (GSDMA, GSDMB). Furthermore, DNA methylation in this region has been implicated as a potential modifier of the genetic risk of asthma development. To further characterize the effect of DNA methylation, we examined the impact of treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) that causes DNA demethylation, on expression and promoter methylation of the five 17q12-q21 genes in the human airway epithelium cell line NuLi-1, embryonic kidney epithelium cell line 293T and human adenocarcinoma cell line MCF-7. 5-aza-dC treatment led to upregulation of expression of GSDMA in all three cell lines. ZPBP2 was upregulated in NuLi-1, but remained repressed in 293T and MCF-7 cells, whereas ORMDL3 was upregulated in 293T and MCF-7 cells, but not NuLi-1. Upregulation of ZPBP2 and GSDMA was accompanied by a decrease in promoter methylation. Moreover, 5-aza-dC treatment modified allelic expression of ZPBP2 and ORMDL3 suggesting that different alleles may respond differently to treatment. We also identified a polymorphic CTCF-binding site in intron 1 of ORMDL3 carrying a CG SNP rs4065275 and determined its methylation level. The site's methylation was unaffected by 5-aza-dC treatment in NuLi-1 cells. We conclude that modest changes (8-13%) in promoter methylation levels of ZPBP2 and GSDMA may cause substantial changes in RNA levels and that allelic expression of ZPBP2 and ORMDL3 is mediated by DNA methylation.
Asunto(s)
Metilación de ADN , Células Epiteliales/metabolismo , Factor de Transcripción Ikaros/genética , Proteínas de Neoplasias/genética , Alelos , Secuencias de Aminoácidos , Azacitidina/química , Sitios de Unión , Línea Celular , Proteínas del Huevo/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Células HEK293 , Humanos , Células MCF-7 , Proteínas de la Membrana/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Regulación hacia ArribaRESUMEN
In cystic fibrosis (CF), chronic respiratory infections result in an exaggerated and uncontrolled inflammatory response that ultimately lead to a decrease in pulmonary function. We have previously described the presence of the alarmin IL-33 in lung explants from CF patients. The signals regulating IL-33 expression in the airway epithelium following a gram-negative bacterial infection are currently unknown. Our objective was to characterize the pathways in CF airway epithelial cells (AECs) leading to an increase in IL-33 expression. We found that, in CF AECs expressing a deletion of a phenylalanine at position 508 of the gene coding for Cystic Fibrosis Transmembrane Conductance Regulator (CFTRdelF508), exposure to live Pseudomonas aeruginosa upregulates IL-33 via the TLR2 and TLR5 signaling pathways. This up-regulation can be partially or fully reverted by pre-incubating CFTRdelF508 AECs with a CFTR corrector (VX-809) and/or a CFTR potentiator (VX-770). Similarly, incubation with the CFTR corrector and/or the CFTR potentiator also decreased IL-8 expression in response to infection. Moreover, using different protein kinase inhibitors that target elements downstream of TLR signaling, we show that the TAK1âIKKßâTPL2âMKK1/MKK2 pathway regulates IL-33 expression following an infection with P. aeruginosa. Our findings represent the first characterization of the signals regulating IL-33 expression in CF airway epithelial cells in response to a bacterial infection.
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OBJETIVO: Determinar a prevalência de sintomas depressivos (SD) e a sua relação com aspectos funcionais, sociodemográficos e antropométricos em idosos da Estratégia Saúde da Família de Porto Alegre (RS). MÉTODOS: Trata-se de um estudo transversal prospectivo e analítico com amostra aleatória de 509 idosos de 30 unidades básicas de saúde. Analisaram-se idade, faixa etária, sexo, estado civil, escolaridade, peso, altura, índice de massa corporal, funcionalidade, atividades básicas e instrumentais de vida diária e presença de SD. Para análise estatística, utilizou-se o teste χ2 (bivariada) e de regressão logística (multivariada). RESULTADOS: A prevalência de SD na amostra foi de 35,4%. O modelo final apresentou associação estatisticamente significativa de SD com sexo feminino (odds ratio OR = 2,87; intervalo de confiança de 95% IC95% 1,929,23), analfabetismo [(OR = 2,13; IC95% 1,895,12), baixa escolaridade (OR = 1,23; IC95% 1,052,74), dependência em atividades instrumentais de vida diária (OR = 4,03; IC95% 1,689,64), baixos escores no teste senta/levanta (OR = 0,89; IC95% 0,820,96) e menor força de preensão manual (OR = 0,95; IC95% 0,930,98). CONCLUSÃO: A prevalência dos SD observada foi alta, e, ante as associações apresentadas, sugere-se que mulheres analfabetas ou com baixa escolaridade, com dificuldade em atividades instrumentais de vida diária, mais fracas e lentas devem ser investigadas quanto à presença de SD, pelo risco de desenvolvê-los.
OBJECTIVE: The aim of this study was to determine the prevalence of depressive symptoms (DS) and their relationship with functional, sociodemographic and anthropometric aspects in the older adults from the Family Health Strategy of Porto Alegre/ RS. METHOD: This is a cross-sectional, prospective and analytical study, with a random sample of 509 older adults from 30 public health units. The following variables were analyzed: age, age group, sex, marital status, schooling, weight, height and body mass index, functionality, activities of daily living, both basic and instrumental, and the presence of DS. For the statistical analyses, the bivariate qui-square test and the multivariate logistic regression were used. RESULTS: The prevalence of DS in this sample was 35,5%. The final model presented a significant statistical association of DS with female gender (OR = 2.87; IC95% 19.2-9.23), illiteracy (OR = 2.13; IC95% 1.895.12), low schooling (OR = 1.23; IC95% 1.052.74), dependence on IADL (OR = 4.03; IC95% 1.689.64), low scores in the sit-to-stand test (OR = 0.89; IC95% 0.820.96) and lower HGS (OR = 0.95; IC95% 0.930.98). CONCLUSION: The prevalence of DS observed was high (35.4%) and, considering the associations presented, it is suggested that illiterate or poorly educated, weaker and slower women with difficulty in IADL should be investigated for the presence of depressive symptoms, for being at the risk of developing them.
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Humanos , Masculino , Femenino , Anciano , Atención Primaria de Salud , Depresión/psicología , Depresión/epidemiología , Fuerza Muscular/fisiología , Brasil/epidemiología , Actividades Cotidianas/psicología , Velocidad al Caminar , Servicios de Salud para AncianosRESUMEN
OBJETIVO: Estudar a possível relação entre qualidade de vida e características sociodemográficas, antropométricas, funcionais e de atividade física em idosos da Estratégia Saúde da Família de Porto Alegre (RS). MÉTODOS: Estudo transversal e analítico com idosos (≥ 60 anos). Os dados foram coletados de forma prospectiva em amostra aleatória de 30 unidades de saúde. As variáveis pesquisadas foram: sociodemográficas (idade, estado civil, escolaridade); antropométricas (peso, altura, índice de massa corporal); e funcionais (velocidade de marcha, força de preensão manual, teste senta/levanta). Foi aplicada a escala de qualidade de vida de Flanagan e o questionário de Minnesota de atividade física e de lazer para o nível de atividade física. Analisaram-se os dados utilizando regressão logística pelo método backward conditional. RESULTADOS: Entre os 577 idosos avaliados (68,5 ± 6,4 anos; 63,7% mulheres), a qualidade de vida de 87% foi classificada como alta. No modelo multivariado inicial (saturado), foram consideradas variáveis preditoras de qualidade de vida: sexo, convivência marital, tempo gasto para caminhar 10 m, escore do teste senta/levanta, força de preensão manual e atividade física moderada, intensa e total. O modelo final (seis etapas) foi composto de quatro variáveis: conviver maritalmente, maior escore do teste senta/levanta, maior força de preensão manual e prática de atividade física intensa. CONCLUSÃO: Conforme observado, a alta qualidade de vida relacionou-se a idosos que convivem maritalmente, apresentam maior força de membros superiores e inferiores e despendem mais tempo na prática de atividade física intensa.
OBJECTIVE: To study the possible relation between quality of life and sociodemographic, anthropometric, functional and physical activity characteristics in older users of the Family Health Strategy in Porto Alegre-RS. METHODS: Cross-sectional and analytical study with older subjects (≥ 60 years). Data were prospectively collected in a random sample of 30 health units. The following variables were analyzed: sociodemographic (age, marital status, education); anthropometric (weight, height, body mass index); functional (walking speed, handgrip strength, Sit/Stand test). The Flanagan Quality of Life Scale and the Minnesota Physical Activity and Leisure Questionnaire (level of physical activity) were applied. Logistic Regression (Backward Conditional Method) was used for data analysis. RESULTS: Among the 577 older subjects evaluated (68.5 ± 6.4 years; 63.7% women), the majority (87%) presented high quality of life. In the initial multivariate (saturated) model, the following variables were considered as predictors of quality of life: gender, marital coexistence, time spent walking 10 m, higher Sit/Stand test score, handgrip strength, moderate, intense and total physical activity. The final model (6 steps) consisted of four variables: cohabitation, higher Sit/Stand test score, higher handgrip strength and engagement in intense physical activity. CONCLUSION: As observed, a high quality of life was related to older people who lived with a partner, presented higher upper and lower limb strength, and spent more time in the practice of intense physical activity.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Atención Primaria de Salud , Calidad de Vida , Salud del Anciano , Actividad Motora , Indicadores de Calidad de Vida , Fuerza de la Mano/fisiología , FragilidadRESUMEN
Objective: to determine the prevalence of body image satisfaction in elderly subjects, as well as its relationship with nutritional status, anthropometric indicators and quality of life. Method: a cross-sectional, descriptive and analytical study was carried out with elderly individuals from Primary Care units (Family Health Strategy) from all the health districts of Porto Alegre, in the state of Rio Grande do Sul. The variables studied were: sociodemographic (gender; age; marital status and schooling), anthropometric (weight; height; body mass index; arm, calf, waist and hip circumference; waist-hip ratio and triceps skinfold), nutritional (Mini Nutritional Assessment), and clinical (quality of life; body image satisfaction). The Stunkard Silhouettes Scale, the Mini Nutritional Assessment and the Flanagan quality of life scale were applied. For data analysis, logistic regression (five steps) was performed with the Conditional Backward method. Results: a total of 532 elderly users (68.96 (7.14) years) were evaluated, mostly women (64.8%) who were dissatisfied with their body image (71.7%). The predictors of body image satisfaction were: eutrophic/underweight body mass index, eutrophy/insufficient arm circumference, and higher mean quality of life scores. Conclusion: in general, a low prevalence of body image satisfaction was identified among the elderly. Subjects with lower body mass index, smaller arm circumference measures and better quality of life had a greater chance of being satisfied with their body image.
Objetivo: determinar a prevalência da satisfação com a imagem corporal em idosos, bem como a sua relação com o estado nutricional, indicadores antropométricos e qualidade de vida. Método: estudo transversal, descritivo e analítico desenvolvido com idosos provenientes de unidades da Estratégia Saúde da Família de todos os distritos sanitários de Porto Alegre/Rio Grande do Sul. As variáveis pesquisadas foram: sociodemográficas (sexo; idade; estado civil e escolaridade), antropométricas (peso; altura; índice da massa corporal; circunferências do braço, panturrilha, cintura e quadril; razão cintura-quadril e dobra cutânea triciptal), nutricional (Mini Avaliação Nutricional), e clínicas (qualidade de vida; satisfação com a imagem corporal). Foram aplicadas a Escala de Silhuetas de Stunkard (imagem corporal), a Mini Avaliação Nutricional e a escala de qualidade de vida de Flanagan. Para análise dos dados foi realizada regressão logística (cinco etapas) com o método Backward condicional. Resultados: foram avaliados 532 usuários idosos [68,96 (7,14) anos], em sua maioria mulheres (64,8%) e insatisfeitas com sua imagem corporal (71,7%). Foram consideradas variáveis preditoras da satisfação com a imagem corporal: índice de massa corporal eutrófico/baixo peso, circunferência do braço eutrofia/insuficiente e média mais alta na qualidade de vida. Conclusão: identificou-se baixa prevalência da satisfação com a imagem corporal entre os idosos em geral. Aqueles com menor índice de massa corporal, menores medidas de circunferência do braço e melhor qualidade de vida apresentaram maiores chances de serem satisfeitos com a sua imagem corporal.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Calidad de Vida , Imagen Corporal , Antropometría , Estado Nutricional , Salud del AncianoRESUMEN
ABSTRACT: Body image, according to the definition by Ledoux et al.(1) is "the systematic, cognitive, affective, conscious, and unconscious representation that people have concerning their bodies during their biological development and throughout their social relationships". Objective: To determine the prevalence of body image satisfaction (BIS) and its relationship with sociodemographic, functional and clinical aspects in older adults. Methods: A cross-sectional, analytical and prospective study of a random sample of older adults from all health districts of Porto Alegre (30 health units) was conducted. The following aspects were studied: sociodemographic data (sex, age, marital status and education), BIS (Stunkard's scale), functional tests (30 seconds Sit/Stand Test, time to walk 10m, Handgrip Strength - HGS), physical activity (Minnesota Questionnaire) and cognition (Mini-Mental State Examination). Results: Most of the 532 participants were dissatisfied with their body image (92.5%), particularly the women (71.7%). After Binary Logistic Regression (6 steps), BIS predictors were: high scores for the Sit/Stand (OR: 1.13; p=0.013), higher HGS (OR: 1.06; p=0.049), shorter time engaged in physical activity (OR: 0.77; p<0.001). Conclusion: The prevalence of BIS was low and most of the variables analyzed bore no relation to BIS. Notwithstanding, a relationship was found with greater HGS, higher Sit/Stand score and less time engaged in physical activity. Given the scarcity of studies on this subject, our study furthers the knowledge on how body image affects this population group.
RESUMO: A imagem corporal, de acordo com a definição de Ledoux et al.(1), é "a representação sistemática, cognitiva, afetiva, consciente e inconsciente que as pessoas possuem em relação ao seu corpo durante o seu desenvolvimento biológico e ao longo de suas relações sociais". Objetivo: Determinar a prevalência de satisfação com a imagem corporal (BIS) e sua relação com aspectos sociodemográficos, funcionais e clínicos em idosos. Métodos: Estudo transversal, analítico e prospectivo, realizado em uma amostra aleatória de idosos de todos os distritos sanitários de Porto Alegre (30 unidades de saúde). Os seguintes aspectos foram estudados: dados sociodemográficos (sexo, idade, estado civil e escolaridade), BIS (escala de Stunkard), testes funcionais (30 segundos Sit/Stand Test, tempo de caminhada 10m, Handgrip Strength - HGS) atividade física (Minnesota Questionnaire) e cognição (Mini Mental State Examination). Resultados: A maioria dos 532 participantes estava insatisfeita com a imagem corporal (92,5%), particularmente as mulheres (71,7%). Após a Regressão Logística Binária (6 passos), os preditores do BIS foram: escores altos para o sentar/levantar (OR: 1,13; p=0,013), maior FP (OR: 1,06; p=0,049), menor tempo gasto em atividade física (OR: 0,77; p<0,001). Conclusão: A prevalência do BIS foi baixa e a maioria das variáveis ââanalisadas não apresentou relação com o BIS. Não obstante, foi encontrada uma relação com maior FPP, maior escore de Sit/Stand e menor tempo gasto em atividade física. Devido à escassez de estudos sobre o assunto, nossa pesquisa ajuda a aumentar o conhecimento sobre como a imagem corporal afeta essa parcela da população.