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1.
Clin Gerontol ; 45(2): 272-286, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33719899

RESUMEN

OBJECTIVES: Stress influences metabolic activity and increases risk for cardiovascular disease (CVD). We sought to a) examine feasibility and acceptability of mindfulness-based stress reduction (MBSR) in older adults at risk for CVD, and b) obtain preliminary data on its metabolic impact. METHODS: A pilot RCT was conducted using a pre-post, 2-month follow-up design. Eighty-one individuals with metabolic syndrome and non-normative responses to stress in a previous investigation were invited. Participants were randomized (by sex and stress response) to a 9-week MBSR or a wait-list control group. Feasibility and acceptability were assessed and blood assayed. Between-subjects (MBSR vs waitlist control) ANOVAs on metabolic parameter change scores, and one-way repeated measures ANOVAs (pre-, post-, follow-up) were performed. RESULTS: Thirty-three individuals (41%) responded to invitations, 26 were interested, of whom 19 were randomized (Mage = 67 years, SD = 7.70). Completion rate of MBSR was 72% and overall attendance was 96%. Reported benefits included increased relaxation, greater interpersonal connection, and increased body awareness. MBSR led to a decrease of 15% in LDL cholesterol and 10% in total cholesterol versus 4.5% and 1%, respectively, in the waitlist. Within group analyses showed notable decreases in LDL, triglycerides, and waist circumference post-MBSR and 2 months later. CONCLUSIONS: A RCT was largely feasible and MBSR acceptable to participants. MBSR may lead to sustained decreases in cholesterol levels, warranting development of large-scale research on this topic. CLINICAL IMPLICATIONS: Given the role of stress in CVD, addition of stress management interventions may serve as a useful complement to risk management among older individuals.


Asunto(s)
Enfermedad de la Arteria Coronaria , Atención Plena , Anciano , Colesterol , Humanos , Proyectos Piloto , Estrés Psicológico/terapia
2.
BMC Health Serv Res ; 20(1): 62, 2020 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-31996193

RESUMEN

BACKGROUND: Emergency departments (EDs) in rural and remote areas face challenges in delivering accessible, high quality and efficient services. The objective of this pilot study was to test the feasibility and relevance of the selected approach and to explore challenges and solutions to improve delivery of care in selected EDs. METHODS: We conducted an exploratory multiple case study in two rural EDs in Québec, Canada. A survey filled out by the head nurse for each ED provided a descriptive statistical portrait. Semi-structured interviews were conducted with ED health professionals, decision-makers and citizens (n = 68) and analyzed inductively and thematically. RESULTS: The two EDs differed with regards to number of annual visits, inter-facility transfers and wait time. Stakeholders stressed the influence of context on ED challenges and solutions, related to: 1) governance and management (e.g. lack of representation, poor efficiency, ill-adapted standards); 2) health services organization (e.g. limited access to primary healthcare and long-term care, challenges with transfers); 3) resources (e.g. lack of infrastructure, limited access to specialists, difficult staff recruitment/retention); 4) and professional practice (e.g. isolation, large scope, maintaining competencies with low case volumes, need for continuing education, teamwork and protocols). There was a general agreement between stakeholder groups. CONCLUSIONS: Our findings show the feasibility and relevance of mobilizing stakeholders to identify context-specific challenges and solutions. It confirms the importance of undertaking a larger study to improve the delivery of care in rural EDs.


Asunto(s)
Servicio de Urgencia en Hospital/organización & administración , Mejoramiento de la Calidad/organización & administración , Servicios de Salud Rural/organización & administración , Toma de Decisiones , Estudios de Factibilidad , Encuestas de Atención de la Salud , Personal de Salud/psicología , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Islas , Proyectos Piloto , Investigación Cualitativa , Quebec , Población Rural
3.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899608

RESUMEN

Tolerogenic dendritic cells (toDCs) are crucial to controlling the development of autoreactive T cell responses and the prevention of autoimmunity. We have reported that NOD.CD11cStat5b-CA transgenic mice expressing a constitutively active (CA) form of Stat5b under the control of a CD11c promoter are protected from diabetes and that Stat5b-CA-expressing DCs are tolerogenic and halt ongoing diabetes in NOD mice. However, the molecular mechanisms by which Stat5b-CA modulates DC tolerogenic function are not fully understood. Here, we used bone marrow-derived DCs (BMDCs) from NOD.CD11cStat5b-CA transgenic mice (Stat5b-CA.BMDCs) and found that Stat5b-CA.BMDCs displayed high levels of MHC class II, CD80, CD86, PD-L1, and PD-L2 and produced elevated amounts of TGFß but low amounts of TNFα and IL-23. Stat5b-CA.BMDCs upregulated Irf4 and downregulated Irf8 genes and protein expression and promoted CD11c+CD11b+ DC2 subset differentiation. Interestingly, we found that the histone methyltransferase Ezh2 and Stat5b-CA bound gamma-interferon activated site (GAS) sequences in the Irf8 enhancer IRF8 transcription, whereas Stat5b but not Ezh2 bound GAS sequences in the Irf4 promoter to enhance IRF4 transcription. Injection of Stat5b-CA.BMDCs into prediabetic NOD mice halted progression of islet inflammation and protected against diabetes. Importantly, inhibition of Ezh2 in tolerogenic Stat5b-CA.BMDCs reduced their ability to prevent diabetes development in NOD recipient mice. Taken together, our data suggest that the active form of Stat5b induces tolerogenic DC function by modulating IRF4 and IRF8 expression through recruitment of Ezh2 and highlight the fundamental role of Ezh2 in Stat5b-mediated induction of tolerogenic DC function.


Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Factores Reguladores del Interferón/metabolismo , Factor de Transcripción STAT5/metabolismo , Traslado Adoptivo , Animales , Autoinmunidad/inmunología , Médula Ósea/efectos de los fármacos , Antígeno CD11c/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Dendríticas/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/fisiología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Tolerancia Inmunológica/genética , Tolerancia Inmunológica/inmunología , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones Transgénicos , Factor de Transcripción STAT5/fisiología , Linfocitos T Reguladores/inmunología
4.
Emerg Infect Dis ; 24(10): 1850-1858, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30226164

RESUMEN

Congenital Zika virus syndrome consists of a large spectrum of neurologic abnormalities seen in infants infected with Zika virus in utero. However, little is known about the effects of Zika virus intrauterine infection on the neurocognitive development of children born without birth defects. Using a case-control study design, we investigated the temporal association of a cluster of congenital defects with Zika virus infection. In a nested study, we also assessed the early childhood development of children recruited in the initial study as controls who were born without known birth defects,. We found evidence for an association of congenital defects with both maternal Zika virus seropositivity (time of infection unknown) and symptomatic Zika virus infection during pregnancy. Although the early childhood development assessment found no excess burden of developmental delay associated with maternal Zika virus infection, larger, longer-term studies are needed.


Asunto(s)
Desarrollo Infantil , Exposición Materna/efectos adversos , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/etiología , Efectos Tardíos de la Exposición Prenatal , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiología , Virus Zika , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Anomalías Congénitas/epidemiología , Anomalías Congénitas/etiología , Estudios Transversales , Femenino , Geografía Médica , Historia del Siglo XXI , Humanos , Lactante , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Evaluación del Resultado de la Atención al Paciente , Polinesia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/historia , Vigilancia en Salud Pública , Adulto Joven , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/virología
5.
Br J Cancer ; 117(10): 1442-1449, 2017 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-28926526

RESUMEN

BACKGROUND: Long-term effects of psychosocial interventions to reduce emotional distress, sleep difficulties, and fatigue of breast cancer patients are rarely examined. We aim to assess the effectiveness of three group interventions, based on cognitive behavioural therapy (CBT), yoga, and self-hypnosis, in comparison to a control group at a 9-month follow-up. METHODS: A total of 123 patients chose to participate in one of the interventions. A control group was set up for those who agreed not to participate. Emotional distress, fatigue, and sleep quality were assessed before (T0) and after interventions (T1), and at 3-month (T2) and 9-month follow-ups (T3). RESULTS: Nine months after interventions, there was a decrease of anxiety (P=0.000), depression (P=0.000), and fatigue (P=0.002) in the hypnosis group, and a decrease of anxiety (P=0.024) in the yoga group. There were no significant improvements for all the investigated variables in the CBT and control groups. CONCLUSIONS: Our results showed that mind-body interventions seem to be an interesting psychological approach to improve the well-being of breast cancer patients. Further research is needed to improve the understanding of the mechanisms of action of such interventions and their long-term effects on quality of life.


Asunto(s)
Neoplasias de la Mama/psicología , Terapia Cognitivo-Conductual/métodos , Hipnosis/métodos , Estrés Psicológico/terapia , Yoga , Adulto , Ansiedad/etiología , Ansiedad/terapia , Neoplasias de la Mama/complicaciones , Fatiga/etiología , Fatiga/terapia , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Calidad de Vida/psicología , Autocuidado/métodos , Autocuidado/psicología , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Yoga/psicología
6.
J Autoimmun ; 76: 63-74, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27634616

RESUMEN

Defects in dendritic cells (DCs) development and function lead to autoimmune disorders. Autoimmune diabetes in humans and NOD mice results from a breakdown of self-tolerance, ending in T cell-mediated ß-cell destruction. DCs dysfunction in NOD mice results in part from a defect in the JAK-STAT5 signaling pathway associated with the idd4 susceptibility locus. The involvement of Stat5b in DCs tolerogenic functions remains unknown. We have generated transgenic mice (NOD.CD11cStat5b-CA) expressing a constitutively active form of the Stat5b gene (Stat5b-CA) under control of CD11c promoter. All NOD.CD11cStat5b-CA mice were protected against diabetes. Protection was associated with an increased in the pool and suppressive function of Tregs, a promotion of Th2 and Tc2 immune response and a decreased percentage of CD8+ T cells. Splenic DCs of NOD.CD11cStat5b-CA mice acquired a mature phenotype, promoted and induced better conversion of CD4+CD25-Foxp3- T cells into Tregs (CD4+CD25+Foxp3+ T cells) than DCs of NOD mice. Stat5b-CA.DC-educated CD4+CD25- T cells delayed diabetes onset whereas Stat5b-CA.DC-educated Tregs blocked ongoing diabetes in 8-10 weeks old NOD recipient mice. Importantly, injection of Stat5b.CA.DC to 8-10-week old NOD mice halted diabetes progression and educated their splenocytes to loose their diabetogenic potential when transferred to NOD.SCID mice. Our work is the first to report that an active form of Stat5b restored DCs tolerogenic functions that re-educated Tregs to re-establish and to sustain long-term protective immune response against diabetes in NOD mice.


Asunto(s)
Células Dendríticas/inmunología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/metabolismo , Factor de Transcripción STAT5/metabolismo , Autotolerancia/inmunología , Transducción de Señal , Animales , Autoantígenos/inmunología , Autoinmunidad , Biomarcadores , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/metabolismo , Diabetes Mellitus Tipo 1/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Inmunofenotipificación , Ratones , Ratones Endogámicos NOD , Ratones Transgénicos , Fenotipo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
7.
Gerontology ; 62(5): 477-90, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26812523

RESUMEN

BACKGROUND: Healthy elderly individuals are particularly prone to catastrophic events at any moment of their lives. One stressful event for individuals aged 65 and older is a fall that results in a fracture of the hip (HF). HF causes a state of inflammation that may affect immune responses. In this connection, we have reported that HF induced alterations in neutrophil functions. OBJECTIVE: To assess the impact of HF on classical (cM), intermediate (iM) and non-classical (ncM) monocyte subsets. METHODS: Distribution, functions (chemotaxis, phagocytosis, superoxide production and cytokine production), phenotype and activation (NF-x03BA;B and PI3K) were evaluated in monocyte subsets before surgery and 6 weeks and 6 months after the event. RESULTS: The distribution of cM and ncM was unchanged, but iM transiently increased before surgery. Sustained increases (iM response to CCL2 and CX3CL1) and decreases (cM and ncM response to CCL2) in chemotaxis were observed. Phagocytosis and superoxide production were impaired in cM but not in iM or ncM. Sustained expression of HLA-DR occurred in cM but not in iM and ncM. Sustained decreased expression of CD11b occurred only in ncM. Sustained decreases (cM and ncM) and increases (iM) in CCR2 expression were observed. An elevated expression of CX3CR1 was found only in iM. cM produced elevated quantities of TNFα. There was a transient oxidative burst of production before surgery in iM and a sustained decrease in ncM. IL-10 production was severely impaired in cM and decreased in iM prior to surgery. Sustained activation (cM), inhibition (ncM) and transient activation (iM) of NF-x03BA;B were observed. Activation of PI3K was severely impaired in cM and ncM but was sustained in iM. CONCLUSION: HF had more impact on cM and ncM functions than on iM. HF triggered a switch in cM functions from phagocytic to inflammatory elevated TNFα-producing cells. These changes may impact clinical outcomes of HF with respect to inflammation, opportunistic infections and physical recovery.


Asunto(s)
Envejecimiento/fisiología , Fracturas de Cadera , Monocitos , Factor de Necrosis Tumoral alfa/análisis , Anciano , Quimiotaxis/fisiología , Citocinas/metabolismo , Femenino , Fracturas de Cadera/metabolismo , Fracturas de Cadera/patología , Humanos , Estudios Longitudinales , Masculino , Monocitos/patología , Monocitos/fisiología , Periodo Perioperatorio , Fagocitosis/fisiología , Fosfatidilinositol 3-Quinasas/análisis , Superóxidos/metabolismo
8.
Semin Immunol ; 24(5): 331-41, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22560929

RESUMEN

Components of the innate immune response, including neutrophils and macrophages, are the first line of defense against infections. Their role is to initiate an inflammatory response, phagocyte and kill pathogens, recruit natural killer cells (NK), and facilitate the maturation and migration of dendritic cells that will initiate the adaptive immune response. Extraordinary advances have been made in the last decade on the knowledge of the receptors and mechanisms used by cells of the innate immunity not only to sense and eliminate the pathogen but also to communicate each other and collaborate with cells of adaptive immunity to mount an effective immune response. The analysis of innate immunity in elderly humans has evidenced that aging has a profound impact on the phenotype and functions of these cells. Thus altered expression and/or function of innate immunity receptors and signal transduction leading to defective activation and decreased chemotaxis, phagocytosis and intracellular killing of pathogens have been described. The phenotype and function of NK cells from elderly individuals show significant changes that are compatible with remodeling of the different NK subsets, with a decrease in the CD56bright subpopulation and accumulation of the CD56dim cells, in particular those differentiated NK cells that co-express CD57, as well as a decreased expression of activating natural cytotoxicity receptors. These alterations can be responsible of the decreased production of cytokines and the lower per-cell cytotoxicity observed in the elderly. Considering the relevance of these cells in the initiation of the immune response, the possibility to reactivate the function of innate immune cells should be considered in order to improve the response to pathogens and to vaccination in the elderly.


Asunto(s)
Senescencia Celular , Inmunidad Innata , Receptores Inmunológicos/inmunología , Animales , Células Dendríticas/inmunología , Humanos , Neutrófilos/inmunología
9.
Rev Invest Clin ; 68(2): 84-91, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27103044

RESUMEN

Aging is a complex phenomenon leading to numerous changes in the physiological systems of the body. One of the most important changes, called immunosenescence, occurs in the immune system. Immunosenescence covers changes in the innate and the adaptive immune systems and is associated with a low-grade inflammation called inflammaging. Aging, likely via inflammaging, is also associated with the emergence of chronic diseases including cardiovascular and neurodegenerative diseases, cancer, and diabetes mellitus type 2. The origin of this inflammaging is not known with certainty, but several concurrent contributing factors have been suggested, such as aging-associated changes in the innate and adaptive immune response, chronic antigenic stimulation, the appearance of endogenous macromolecular changes, and the presence of senescent cells exhibiting a senescence-associated secretory phenotype. A better understanding of the multiple biological phenomena leading to these diseases via the immunosenescence associated with inflammaging provides a powerful target for interventions to increase the healthspan of elderly subjects.


Asunto(s)
Envejecimiento/fisiología , Inmunosenescencia/fisiología , Inflamación/fisiopatología , Inmunidad Adaptativa/inmunología , Anciano , Envejecimiento/inmunología , Animales , Enfermedad Crónica , Humanos , Inmunidad Innata/inmunología , Inmunosenescencia/inmunología , Inflamación/inmunología
10.
Biogerontology ; 16(1): 85-98, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25376108

RESUMEN

Amyloid plaques, the hallmark of Alzheimer's disease (AD), contain fibrillar ß-amyloid (Aß) 1-40 and 1-42 peptides. Herpes simplex virus 1 (HSV-1) has been implicated as a risk factor for AD and found to co-localize within amyloid plaques. Aß 1-40 and Aß 1-42 display anti-bacterial, anti-yeast and anti-viral activities. Here, fibroblast, epithelial and neuronal cell lines were exposed to Aß 1-40 or Aß 1-42 and challenged with HSV-1. Quantitative analysis revealed that Aß 1-40 and Aß 1-42 inhibited HSV-1 replication when added 2 h prior to or concomitantly with virus challenge, but not when added 2 or 6 h after virus addition. In contrast, Aß 1-40 and Aß 1-42 did not prevent replication of the non-enveloped human adenovirus. In comparison, antimicrobial peptide LL-37 prevented HSV-1 infection independently of its sequence of addition. Our findings showed also that Aß 1-40 and Aß 1-42 acted directly on HSV-1 in a cell-free system and prevented viral entry into cells. The sequence homology between Aß and a proximal transmembrane region of HSV-1 glycoprotein B suggested that Aß interference with HSV-1 replication could involve its insertion into the HSV-1 envelope. Our data suggest that Aß peptides represent a novel class of antimicrobial peptides that protect against neurotropic enveloped virus infections such as HSV-1. Overproduction of Aß peptide to protect against latent herpes viruses and eventually against other infections, may contribute to amyloid plaque formation, and partially explain why brain infections play a pathogenic role in the progression of the sporadic form of AD.


Asunto(s)
Enfermedad de Alzheimer/virología , Péptidos beta-Amiloides/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Replicación Viral/efectos de los fármacos , Enfermedad de Alzheimer/epidemiología , Péptidos beta-Amiloides/uso terapéutico , Línea Celular , Línea Celular Tumoral , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Células Epiteliales/virología , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Fibroblastos/virología , Herpes Simple/prevención & control , Herpesvirus Humano 1/fisiología , Humanos , Neuroglía/efectos de los fármacos , Neuroglía/patología , Neuroglía/virología , Fragmentos de Péptidos/uso terapéutico , Placa Amiloide/virología , Factores de Riesgo
11.
BMC Health Serv Res ; 15: 572, 2015 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-26700302

RESUMEN

BACKGROUND: Rural emergency departments (EDs) constitute crucial safety nets for the 20% of Canadians who live in rural areas. Pilot data suggests that the province of Québec appears to provide more comprehensive access to services than do other provinces. A difference that may be attributable to provincial policy/guidelines "the provincial ED management Guide". The aim of this study was to provide a detailed description of rural EDs in Québec and utilization of the provincial ED management Guide. METHODS: We selected EDs offering 24/7 medical coverage, with hospitalization beds, located in rural or small towns. We collected data via telephone, paper, and online surveys with rural ED/hospital staff. Data were also collected from Québec's Ministry of Health databases and from Statistics Canada. We computed descriptive statistics, ANOVA and t-tests were used to examine the relationship between ED census, services and inter-facility transfer requirements. RESULTS: A total of 23 of Québec's 26 rural EDs (88%) consented to participate in the study. The mean annual ED visits was 18 813 (Standard Deviation = 6 151). Thirty one percent of ED physicians were recent graduates with fewer than 5 years of experience. Only 6 % had residency training or certification in emergency medicine. Teams have good local access (24/7) to diagnostic equipment such as CT scanner (74%), intensive unit care (78%) and general surgical services (78%), but limited access to other consultants. Sixty one percent of participants have reported good knowledge of the provincial ED management Guide, but only 23% of them have used the guidelines. Furthermore, more than 40% of EDs were more than 300 km from levels 1 to 2 trauma centers, and only 30% had air transport access. CONCLUSIONS: Rural EDs in Québec are staffed by relatively new graduates working as solo physicians in well-resourced and moderately busy (by rural standards) EDs. The provincial ED management Guide may have contributed to this model of service attribution. However, the majority of rural ED staff report limited knowledge or use of the provincial ED management Guide and increased efforts at disseminating this Guide are warranted.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Análisis de Varianza , Certificación , Competencia Clínica/normas , Estudios Transversales , Manejo de la Enfermedad , Medicina de Emergencia/normas , Medicina de Emergencia/estadística & datos numéricos , Adhesión a Directriz , Conocimientos, Actitudes y Práctica en Salud , Accesibilidad a los Servicios de Salud/normas , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Hospitales Rurales/estadística & datos numéricos , Humanos , Internado y Residencia/normas , Internado y Residencia/estadística & datos numéricos , Tiempo de Internación , Médicos/normas , Médicos/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Quebec , Servicios de Salud Rural/estadística & datos numéricos , Encuestas y Cuestionarios , Tiempo de Tratamiento
12.
Cell Commun Signal ; 12: 2, 2014 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-24405902

RESUMEN

BACKGROUND: Immune responses are generally impaired in aged mammals. T cells have been extensively studied in this context due to the initial discovery of their reduced proliferative capacity with aging. The decreased responses involve altered signaling events associated with the early steps of T cell activation. The underlying causes of these changes are not fully understood but point to alterations in assembly of the machinery for T cell activation. Here, we have tested the hypothesis that the T cell pool in elderly subjects displayed reduced functional capacities due to altered negative feedback mechanisms that participate in the regulation of the early steps of T cell activation. Such conditions tip the immune balance in favor of altered T cell activation and a related decreased response in aging. RESULTS: We present evidence that the tyrosine phosphatase SHP-1, a key regulator of T cell signal transduction machinery is, at least in part, responsible for the impaired T cell activation in aging. We used tyrosine-specific mAbs and Western blot analysis to show that a deregulation of the Csk/PAG loop in activated T cells from elderly individuals favored the inactive form of tyrosine-phosphorylated Lck (Y505). Confocal microscopy analysis revealed that the dynamic movements of these regulatory proteins in lipid raft microdomains was altered in T cells of aged individuals. Enzymic assays showed that SHP-1 activity was upregulated in T cells of aged donors, in contrast to young subjects. Pharmacological inhibition of SHP-1 resulted in recovery of TCR/CD28-dependent lymphocyte proliferation and IL-2 production of aged individuals to levels approaching those of young donors. Significant differences in the active (Y394) and inactive (Y505) phosphorylation sites of Lck in response to T cell activation were observed in elderly donors as compared to young subjects, independently of CD45 isoform expression. CONCLUSIONS: Our data suggest that the role of SHP-1 in T cell activation extends to its increased effect in negative feedback in aging. Modulation of SHP-1 activity could be a target to restore altered T cell functions in aging. These observations could have far reaching consequences for improvement of immunosenescence and its clinical consequences such as infections, altered response to vaccination.


Asunto(s)
Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Linfocitos T/inmunología , Adulto , Factores de Edad , Anciano , Regulación hacia Abajo , Inhibidores Enzimáticos/farmacología , Humanos , Interleucina-2/genética , Interleucina-2/metabolismo , Activación de Linfocitos , Microdominios de Membrana/metabolismo , Mutación , Proteína Tirosina Fosfatasa no Receptora Tipo 6/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 6/genética , Pirimidinas/farmacología , Linfocitos T/enzimología , Linfocitos T/metabolismo
13.
BMJ Open ; 14(9): e082391, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266313

RESUMEN

OBJECTIVES: To evaluate the feasibility of the Bali Yoga Programme for Residents (PYB-R), an 8-week virtual yoga-based intervention and determine its impact on the mental health of resident physicians. DESIGN: Single-group repeated measures study. SETTING: Associations from the four postgraduate medical education programmes in Québec, Canada. PARTICIPANTS: Overall, 55 resident physicians were recruited to participate of which 53 (96.4%) completed the assessment pre-PYB-R. The postintervention assessment was completed by 43 residents (78.2%) and 39 (70.9%) completed all phases (including 3-month follow-up). Most were in their first year (43.4%) or second year (32.1%) of residency. The majority were female (81.1%) with a mean age of 28±3.6 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was feasibility as measured by participation in the PYB-R. Secondary outcome measures were psychological variables (anxiety, depression, burn-out, emotional exhaustion, compassion fatigue and compassion satisfaction) and satisfaction with the PYB-R. Residents were further subgrouped based on the quality of work life and a number of PYB-R sessions attended. RESULTS: The attrition rate for programme completion was 19%. Of the 43 residents who completed the PYB-R, 90.6% attended between 6 and 8 sessions. Repeated-measures analysis of variances (ANOVAs) at three time points (baseline, PYB-R completion and 3-month follow-up) confirmed a decrease in scores for depression and anxiety, and an increase in scores for compassion satisfaction. No changes were observed in the other psychological variables evaluated. ANOVAs also confirmed that a better quality of life at work helps develop compassion satisfaction, a protective factor to compassion fatigue. Most participants (92.9%) indicated they were satisfied or very satisfied with the quality of the programme. CONCLUSIONS: A virtual yoga-based programme is feasible and has lasting positive effects for up to 3 months on the mental health of resident physicians. Further research is warranted to validate these findings using a larger sample of residents with a control group.


Asunto(s)
Estudios de Factibilidad , Internado y Residencia , Salud Mental , Calidad de Vida , Yoga , Humanos , Femenino , Quebec , Masculino , Adulto , Médicos/psicología , Ansiedad , Agotamiento Profesional/prevención & control , Agotamiento Profesional/psicología , Depresión/terapia
14.
J Nerv Ment Dis ; 201(9): 753-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23995030

RESUMEN

The aim of this study was to assess the incremental cost-effectiveness ratios (ICERs) of two brief cognitive-behavioral therapy (CBT)-based interventions and a pharmacological treatment, compared with usual care, initiated in the emergency department (ED) for individuals with panic disorder (PD) with a chief complaint of noncardiac chest pain. A total of 69 patients were followed up to 6 months. The primary outcome variables were direct and indirect costs of treatment and PD severity. Panic management (PM) had an ICER of $124.05, per the Anxiety Disorders Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, severity score change (95% confidence interval [CI], $54.63-$314.57), compared with pharmacotherapy (paroxetine), with an ICER of $213.90 (95% CI, $133.51-$394.94), and brief CBT, with an ICER of $309.31 (95% CI, $151.27-$548.28). The pharmacological and CBT interventions were associated with a greater clinical improvement compared with usual care at posttest. PM presented a superior ICER, suggesting that it may be a promising treatment option to implement in EDs.


Asunto(s)
Antidepresivos de Segunda Generación/economía , Antidepresivos de Segunda Generación/uso terapéutico , Dolor en el Pecho/economía , Dolor en el Pecho/terapia , Terapia Cognitivo-Conductual/economía , Trastorno de Pánico/economía , Trastorno de Pánico/terapia , Paroxetina/economía , Paroxetina/uso terapéutico , Psicoterapia Breve/economía , Adulto , Anciano , Anciano de 80 o más Años , Dolor en el Pecho/psicología , Estudios de Cohortes , Análisis Costo-Beneficio/economía , Costos de los Medicamentos/estadística & datos numéricos , Servicio de Urgencia en Hospital/economía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno de Pánico/psicología , Quebec , Adulto Joven
15.
Clin Psychol Psychother ; 20(1): 67-76, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-21793103

RESUMEN

Body dysmorphic disorder (BDD) is a debilitating disorder characterized by an excessive pre-occupation with an imagined or very slight defect in one's physical appearance. Despite the overall success of cognitive behavioural therapy (CBT) in treating BDD, some people do not seem to benefit as much from this approach. Those with high overvalued ideation (OVI), for instance, have been shown to not respond well with CBT. The purpose of this study was to evaluate the efficacy of an inference-based therapy (IBT) in treating BDD. IBT is a cognitive intervention that was first developed for obsessive-compulsive disorder with high OVI, but whose focus on beliefs can also apply to a BDD population. IBT conceptualizes BDD obsessions (e.g., 'I feel like my head is deformed') as idiosyncratic inferences arrived at through inductive reasoning processes. Such primary inferences represent the starting point of obsessional doubt and the treatment focuses on addressing the faulty inferences that maintain the doubt. Thirteen BDD participants, of whom 10 completed, underwent a 20-week IBT for BDD. The participants improved significantly over the course of therapy, with large diminutions in BDD and depressive symptoms. OVI also decreased throughout therapy and was not found to be related to reduction in BDD symptoms. Although a controlled-trial comparing CBT with IBT is needed, it is proposed that IBT constitutes a promising treatment alternative for BDD especially in cases where OVI is high.


Asunto(s)
Trastorno Dismórfico Corporal/terapia , Terapia Cognitivo-Conductual/métodos , Adolescente , Adulto , Anciano , Trastorno Dismórfico Corporal/psicología , Imagen Corporal/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
16.
Cell Immunol ; 272(2): 259-68, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22070873

RESUMEN

Tolerogenic dendritic cells represent a promising immunotherapy in autoimmunity. However, the molecular mechanisms that drive tolerogenic DCs functions are not well understood. We used GM-CSF or GM-CSF+IL-4 to generate tolerogenic (GM/DCs) and immunogenic (IL-4/DCs) BMDCs from NOD mice, respectively. GM/DCs were resistant to maturation, produced large amounts of IL-10 but not IL-12p70. GM/DCs displayed a reduced capacity to activate diabetogenic CD8(+) T-cells and were efficient to induce Tregs expansion and conversion. LPS stimulation triggered ERK1/2 activation that was sustained in GM/DCs but not in IL-4/DCs. ERK1/2 and AP-1 were involved in IL-10 production in GM/DCs but not in their resistance to maturation. Supershift analysis showed that NF-κB DNA binding complex contains p52 and p65 in GM/DCs, whereas it contains p52, p65 and RelB in IL-4/DCs. ChIP experiments revealed that p65 was recruited to IL-10 promoter following LPS stimulation of GM/DCs whereas its binding to IL-12p35 promoter was abolished. Our results suggest that immunoregulatory functions of GM/DCs are differentially regulated by ERK1/2, AP-1 and NF-κB pathways.


Asunto(s)
Células de la Médula Ósea/inmunología , Células Dendríticas/inmunología , Sistema de Señalización de MAP Quinasas/inmunología , FN-kappa B/inmunología , Factor de Transcripción AP-1/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/inmunología , Procesos de Crecimiento Celular/inmunología , Inmunoprecipitación de Cromatina/métodos , Proteínas de Unión al ADN/inmunología , Proteínas de Unión al ADN/metabolismo , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-12/inmunología , Subunidad p35 de la Interleucina-12/genética , Subunidad p35 de la Interleucina-12/inmunología , Interleucina-4/inmunología , Lipopolisacáridos/inmunología , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos NOD , Subunidad p52 de NF-kappa B/inmunología , Fenotipo , Regiones Promotoras Genéticas , Linfocitos T Reguladores/inmunología , Factor de Transcripción ReIA/inmunología , Factor de Transcripción ReIB/inmunología
17.
Int Psychogeriatr ; 24(9): 1429-36, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22717010

RESUMEN

BACKGROUND: Frailty is a complex health state of increased vulnerability associated with adverse outcomes such as disability, falls, hospitalization, and death. Along with physical impairments, cognition and quality of life may be affected in frail older adults. Yet, evidence is still lacking. The aim of this study was to compare frail and non-frail older adults on physical, cognitive, and psychological dimensions. METHODS: Thirty-nine frail and 44 non-frail elders were compared on several measures of physical capacity, cognition, and quality of life. Frailty status was based on a geriatric examination and scored using the Modified Physical Performance Test. RESULTS: After controlling for demographic and medical characteristics, physical capacity measures (i.e. functional capacities, physical endurance, gait speed, and mobility) were significantly lower in frail participants. Frail participants showed reduced performances in specific cognitive measures of executive functions and processing speed. On the quality of life dimension, frail elders reported poor self-perceptions of physical capacity, cognition, affectivity, housekeeping efficacy, and physical health. CONCLUSION: In addition to the reduced physical capacity, frailty might affect selective components of cognition and quality of life. These dimensions should be investigated in intervention programs designed for frail older adults.


Asunto(s)
Cognición , Anciano Frágil/estadística & datos numéricos , Aptitud Física , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Función Ejecutiva , Femenino , Anciano Frágil/psicología , Evaluación Geriátrica , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Resistencia Física , Aptitud Física/psicología
18.
J Behav Med ; 35(5): 557-68, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22068879

RESUMEN

Cognitive deficits are frequent after coronary artery bypass graft surgery (CABG) in the elderly population. In fact, memory and attention deficits can persist several months after the surgery. Recent studies with healthy older adults have shown that memory and attention can be improved through cognitive training programs. The present study examined whether memory training (method of loci and story generation) and attentional training (dual-task computerized training) could improve cognitive functions in patients aged 65 years and older who underwent CABG surgery. Participants (n = 51) were assigned to one of three groups: (1) control group (tested at 1, 3 and 6 months after the surgery), (2) attention training followed by memory training, (3) memory training followed by attention training (groups 2 and 3: tested at 1, 2, 3 and 6 months after the surgery). The trainings took place between the 6th and 10th week following the surgery. The three groups were compared before and after each training program using attention and memory tests and neuropsychological tests. The results showed that attention and memory trainings lead to significant improvement in the cognitive domain that was trained. It thus seems that cognitive training can be a promising tool to enhance cognitive functions after a CABG surgery.


Asunto(s)
Atención , Trastornos del Conocimiento/terapia , Terapia Cognitivo-Conductual , Puente de Arteria Coronaria/efectos adversos , Memoria , Anciano , Trastornos del Conocimiento/etiología , Puente de Arteria Coronaria/psicología , Femenino , Humanos , Masculino , Análisis y Desempeño de Tareas , Resultado del Tratamiento
19.
Behav Cogn Psychother ; 40(2): 129-47, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21929830

RESUMEN

BACKGROUND: Panic disorder (PD) is a common, often unrecognized condition among patients presenting with chest pain to the emergency departments (ED). Nevertheless, psychological treatment is rarely initiated. We are unaware of studies that evaluated the efficacy of brief cognitive-behavioural therapy (CBT) for this population. AIM: Evaluate the efficacy of two brief CBT interventions in PD patients presenting to the ED with chest pain. METHOD: Fifty-eight PD patients were assigned to either a 1-session CBT-based panic management intervention (PMI) (n = 24), a 7-session CBT intervention (n = 19), or a usual-care control condition (n = 15). A structured diagnostic interview and self-reported questionnaires were administered at pre-test, post-test, 3- and 6-month follow-ups. RESULTS: Statistical analysis showed significant reduction in PD severity following both interventions compared to usual care control condition, but with neither showing superiority compared to the other. CONCLUSIONS: CBT-based interventions as brief as a single session initiated within 2 weeks after an ED visit for chest pain appear to be effective for PD. Given the high prevalence of PD in emergency care settings, greater efforts should be made to implement these interventions in the ED and/or primary care setting.


Asunto(s)
Dolor en el Pecho/psicología , Terapia Cognitivo-Conductual/métodos , Servicio de Urgencia en Hospital , Astenia Neurocirculatoria/terapia , Trastorno de Pánico/psicología , Trastorno de Pánico/terapia , Psicoterapia Breve/métodos , Adulto , Anciano , Anciano de 80 o más Años , Agorafobia/diagnóstico , Agorafobia/psicología , Agorafobia/terapia , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Entrevista Psicológica , Masculino , Persona de Mediana Edad , Astenia Neurocirculatoria/diagnóstico , Astenia Neurocirculatoria/psicología , Trastorno de Pánico/diagnóstico , Quebec , Adulto Joven
20.
J Alzheimers Dis Rep ; 6(1): 599-606, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36275414

RESUMEN

Background: Unravelling the mystery of Alzheimer's disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the literature, for instance, both the deposition of the amyloid-ß peptide (Aß) and the intracellular neurofibrillary tangles could occur within the brain without any cognitive pathology. Thus, these paradoxes suggest that something more fundamental is at play in the onset of the disease and other key and related pathomechanisms must be investigated. Objective: The present study follows our previous investigations on the infectious hypothesis, which posits that some pathogens are linked to late onset AD. Our studies also build upon the finding that Aß is a powerful antimicrobial agent, produced by neurons in response to viral infection, capable of inhibiting pathogens as observed in in vitro experiments. Herein, we ask what are the molecular mechanisms in play when Aß neutralizes infectious pathogens? Methods: To answer this question, we probed at nanoscale lengths with FRET (Förster Resonance Energy Transfer), the interaction between Aß peptides and glycoprotein B (responsible of virus-cell binding) within the HSV-1 virion. Results: The experiments show an energy transfer between Aß peptides and glycoprotein B when membrane is intact. No energy transfer occurs after membrane disruption or treatment with blocking antibody. Conclusion: We concluded that Aß insert into viral membrane, close to glycoprotein B, and participate in virus neutralization.

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