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1.
Tob Induc Dis ; 21: 109, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37654502

RESUMEN

INTRODUCTION: Literature exploring smoking status and its association with depression among the elderly population using nationwide data in Malaysia is limited. Hence, a nationwide survey to determine the prevalence of smoking and depression among the elderly (aged ≥60 years) population was undertaken. METHODS: This secondary dataset analysis used data from the National Health and Morbidity Survey (NHMS) 2018. Data from 3914 participants were collected on elderly health in the Malaysian population. Sociodemographic characteristics were recorded. Smoking status was grouped as current smokers, former smokers, and non-smokers. A validated Malay language version of the Geriatric Depression Scale (M-GDS-14) was used to screen for depression among the elderly. RESULTS: There was a significant association between smoking status with location, gender, employment status, marital status, ethnicity, education level, income, and depression. Current smokers are significantly higher in rural than urban areas. Among depressed participants, 65.7%, 17.1% and 17.2% were non-smokers, former smokers and current smokers, respectively. Multiple logistic regression showed that single (unmarried/separated/ divorced/widowed) participants were more likely to be depressed compared to married participants (AOR=1.68; 95% CI: 1.16-2.43). Whilst unemployed participants were more likely to be depressed than those who were employed (AOR=1.72; 95% CI: 1.22-2.44). Other Bumiputras were more likely to have depression compared to Malay, Chinese and Indian participants. Participants without formal education were more likely to be depressed compared to those having tertiary education. These participants have a 2-fold increased risk of depression (AOR=2.13; 95% CI: 1.02-4.45). Participants whose monthly salaries were <2000 MYR (AOR=3.67; 95% CI: 1.84-7.31) and 1000-1999 MYR (AOR=2.71; 95% CI: 1.23-5.94) were more likely to have depression compared with those who had received ≥3000 MYR. Ever smokers were more likely to be depressed than non-smokers (AOR=1.68; 95% CI: 1.23-2.29). CONCLUSIONS: Elderly Malaysians are indeed at risk of developing depression particularly if they had ever smoked. Public health awareness and campaigning are pertinent to disseminate these outcomes in order to spread the awareness associated with smoking-related depression.

2.
Anaesthesia ; 78(9): 1153-1161, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37314744

RESUMEN

Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the effect of prophylactic intravenous tranexamic acid on thromboembolic outcomes in patients undergoing non-cardiac surgery. The MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Randomised controlled trials comparing intravenous tranexamic acid with placebo or no treatment in patients undergoing non-cardiac surgery were included. The primary outcome was a composite of peri-operative cardiovascular thromboembolic events, defined as any deep vein thrombosis, pulmonary embolism, myocardial ischaemia/infarction or cerebral ischaemia/infarction. A total of 191 randomised controlled trials (40,621 patients) were included in the review. The primary outcome occurred in 4.5% of patients receiving intravenous tranexamic acid compared with 4.9% of patients in the control group. Our analysis showed that there was no difference between groups for composite cardiovascular thromboembolic events (risk ratio 1.02, 95%CI 0.94-1.11, p = 0.65, I2 0%, n = 37,512). This finding remained robust when sensitivity analysis was performed with continuity correction and in studies with a low risk of bias. However, in trial sequential analysis, our meta-analysis only achieved 64.6% of the required information size. There was no association between intravenous tranexamic acid and seizure rate or mortality rate within 30 days. Intravenous tranexamic acid was associated with a reduced blood transfusion rate compared with control (9.9% vs. 19.4%, risk ratio 0.46, 95%CI 0.41-0.51, p < 0.0001). It was encouraging to see the evidence that the administration of intravenous tranexamic in patients undergoing non-cardiac surgery was not associated with an increased risk of thromboembolic outcomes. However, our trial sequential analysis demonstrated that currently available evidence is not yet sufficient to reach a firm conclusion.


Asunto(s)
Antifibrinolíticos , Infarto del Miocardio , Tromboembolia , Ácido Tranexámico , Humanos , Ácido Tranexámico/efectos adversos , Antifibrinolíticos/efectos adversos , Tromboembolia/prevención & control , Transfusión Sanguínea , Pérdida de Sangre Quirúrgica/prevención & control
3.
Tech Coloproctol ; 27(7): 589-599, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36971849

RESUMEN

PURPOSE: The da Vinci SP® (dVSP) surgical system (Intuitive Surgical, Sunnyvale, CA, USA), a robotic platform designed for single-incision surgery, overcame the need for multiple ports in traditional robotic surgery and issues including triangulation and retraction in single-incision laparoscopic surgery. However, previous studies only included case reports or series with small sample sizes. The aim of this study was to assess the safety and performance of the dVSP surgical system and its instruments and accessories for colorectal procedures. METHODS: The medical records of patients who had surgery with the dVSP from March 2019 to September 2021 at Ewha Womans University Seoul Hospital were investigated. The pathologic and follow-up data of patients who had malignant tumors were analyzed separately to evaluate oncological safety. RESULTS: Fifty patients (26 male and 24 female) with a median age of 59 years (interquartile range 52.5-63.0 years) were enrolled. The procedures included low anterior resection with total mesorectal excision (n = 16), sigmoid colectomy with complete mesocolic excision and central vessel ligation (CME + CVL) (n = 14), right colectomy with CME + CVL (n = 9), left colectomy with CME + CVL (n = 4), right colectomy (n = 6), and sigmoid colectomy (n = 1). Operative time significantly decreased after 25 cases (early phase vs. late phase; operative time 295.0 min vs. 250.0 min, p = 0.015; docking time 16.0 min vs. 12.0 min, p = 0.001; console time 212.0 min vs. 190.0 min, p = 0.019). Planned procedures were successfully completed in all patients. Postoperative outcomes were acceptable with only six cases of mild adverse events through a 3-month follow-up. No local recurrence and only one case of systemic recurrence occurred within 1 year postoperatively. CONCLUSIONS: This study demonstrated the surgical and oncological safety and feasibility of dVSP, which may be a novel surgical platform for colorectal surgery.


Asunto(s)
Cirugía Colorrectal , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/métodos , Robótica/métodos , Colectomía/métodos , Tempo Operativo , Estudios Retrospectivos
4.
J Frailty Aging ; 11(4): 348-369, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36346721

RESUMEN

OBJECTIVES: To present the local evidence and final recommendations of the Clinical Practice Guidelines workgroup convened by the Chapter of Geriatricians and the Society for Geriatric Medicine Singapore. The aim is to develop contextualized evidence-based recommendations that facilitate adoption of the Asian Working Group for Sarcopenia (AWGS) 2019 consensus into current practice in Singapore. METHODS: The workgroup drew upon the AWGS'2019 consensus, updated literature review of Singapore studies till 31 Dec 2020, and evidence from recent systematic reviews. From 40 local studies included for data extraction, we constructed evidence tables organized as: definition and epidemiology; diagnosis and evaluation; and treatment and intervention. Twenty recommendations - case-finding, diagnosis, treatment, prevention, research - were developed, and graded for strength and quality using the GRADE approach. Consensus from an expert panel(N=23) was achieved after two rounds of the modified Delphi process. RESULTS: The local prevalence of sarcopenia among community-dwelling older adults ranged from 13.6% to 25%. Most studies adopted the AWGS'2019 and AWGS'2014 criteria. Reported case finding tools include SARC-F, calf circumference (CC) and SARC-CalF. Gender-specific AWGS cut-offs for appendicular skeletal mass were used to define low muscle mass. Different protocols and dynamometers were used to assess handgrip strength, whilst gait speed and 5-times chair stand were commonly used to assess physical performance. RECOMMENDATIONS: We conditionally recommend a case-finding approach in at-risk older adults using validated case-finding tools. Screen-positive individuals should be assessed for 'possible sarcopenia' and underlying causes. For diagnosis, we conditionally recommend using the AWGS'2019 algorithm, and dual-energy X-ray absorptiometry when necessary to determine low lean mass for a confirmatory diagnosis of sarcopenia. For treatment, we strongly recommend resistance-based exercises and conditionally recommend a quality protein-rich diet/protein supplementation, with Vitamin D supplementation for insufficiency (<30 micrograms/L). For prevention, we recommend regular resistance-based physical activity and adequate protein intake (≥1.0g/kg bodyweight). We encourage more research to address local evidence gaps.


Asunto(s)
Sarcopenia , Humanos , Anciano , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Sarcopenia/prevención & control , Fuerza de la Mano , Singapur/epidemiología , Fuerza Muscular/fisiología , Velocidad al Caminar , Tamizaje Masivo/métodos , Evaluación Geriátrica/métodos
5.
QJM ; 115(1): 7-11, 2022 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-32810234

RESUMEN

BACKGROUND: Transient hyperglycaemia in the context of illness with or without known diabetes has been termed as 'stress hyperglycaemia'. Stress hyperglycaemia can result in poor functional outcomes in patients with acute ischaemic stroke (AIS) who underwent mechanical thrombectomy. We investigated the association between stress hyperglycaemia and clinical outcomes in AIS patients undergoing intravenous thrombolysis (IVT). METHODS: We examined 666 consecutive patients with AIS who underwent IVT from 2006 to 2018. All patients had a glycated haemoglobin level (HbA1c) and fasting venous blood glucose measured within 24 h of admission. Stress hyperglycaemia ratio (SHR) was defined as the ratio of the fasting glucose to the HbA1c. Univariate and multivariate analyses were employed to identify predictors of poor functional outcomes (modified Rankin Scale 3-6 at 3 months) after IVT. RESULTS: Three-hundred and sixty-one patients (54.2%) had good functional outcomes. These patients tended to be younger (60.7 ± 12.7 vs. 70 ± 14.4 years, P < 0.001), male (70.7% vs. 51.5%, P < 0.001), had lower prevalence of atrial fibrillation (13.0% vs. 20.7%, P = 0.008) and lower SHR (0.88 ± 0.20 vs. 0.99 ± 26, P < 0.001). Patients with high SHR (≥0.97) were slightly older than those with low SHR (<0.97) and were more likely to have diabetes mellitus. On multivariate analysis, higher SHR was independently associated with poor functional outcomes (adjusted odds ratio 3.85, 95% confidence interval 1.59-9.09, P = 0.003). CONCLUSION: SHR appears to be an important predictor of functional outcomes in patients with AIS undergoing IVT. This may have important implications on the role of glycaemic control in the acute management of ischaemic stroke.


Asunto(s)
Isquemia Encefálica , Hiperglucemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Humanos , Hiperglucemia/tratamiento farmacológico , Masculino , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Resultado del Tratamiento
6.
J Prev Alzheimers Dis ; 8(3): 335-344, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34101792

RESUMEN

BACKGROUND: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. OBJECTIVE: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. DESIGN: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. SETTING: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. MEASUREMENTS: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. RESULTS: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). CONCLUSIONS: The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.


Asunto(s)
Envejecimiento/fisiología , Disfunción Cognitiva , Valor Predictivo de las Pruebas , Medición de Riesgo , Encuestas y Cuestionarios , Anciano , Factores de Riesgo Cardiometabólico , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Estudios de Cohortes , Femenino , Pérdida Auditiva , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Reproducibilidad de los Resultados , Singapur/epidemiología
8.
J Nutr Health Aging ; 24(1): 98-106, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31886815

RESUMEN

OBJECTIVES: To investigate risk factors of incident physical frailty. DESIGN: A population-based observational longitudinal study. SETTING: Community-dwelling elderly with age 55 years and above recruited from 2009 through 2011 in the second wave Singapore Longitudinal Ageing Study-2 (SLAS-2) were followed up 3-5 years later. PARTICIPANTS: A total of 1297 participants, mean age of 65.6 ±0.19, who were free of physical frailty. MEASUREMENTS: Incident frailty defined by three or more criteria of the physical phenotype used in the Cardiovascular Health Study was determined at follow-up. Potential risk factors assessed at baseline included demographic, socioeconomic, medical, psychological factors, and biochemical markers. RESULTS: A total of 204 (15.7%) participants, including 81 (10.87%) of the robust and 123 (22.28%) of the prefrail transited to frailty at follow-up. Age, no education, MMSE score, diabetes, prediabetes and diabetes, arthritis, ≥5 medications, fair and poor self-rated health, moderate to high nutritional risk (NSI ≥3), Hb (g/dL), CRP (mg/L), low B12, low folate, albumin (g/L), low total cholesterol, adjusted for sex, age and education, were significantly associated (p<0.05) with incident frailty. In stepwise selection models, age (year) (OR=1.07, 95%CI=1.03-1.10, p<0.001), albumin (g/L) (OR=0.85, 95%CI=0.77-0.94, p=0.002), MMSE score (OR=0.88, 95%CI=0.78-0.98, p=0.02), low folate (OR=3.72, 95%CI=1.17-11.86, p=0.03, and previous hospitalization (OR=2.26, 95%CI=1.01-5.04,p=0.05) were significantly associated with incident frailty. CONCLUSIONS: The study revealed multiple modifiable risk factors, especially related to poor nutrition, for which preventive measures and early management could potentially halt or delay the development of frailty.


Asunto(s)
Envejecimiento/fisiología , Anciano Frágil/estadística & datos numéricos , Fragilidad/fisiopatología , Evaluación Geriátrica , Estado Nutricional/fisiología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Vida Independiente , Estudios Longitudinales , Masculino , Evaluación Nutricional , Examen Físico , Factores de Riesgo , Singapur , Factores Socioeconómicos
9.
J Nutr Health Aging ; 23(3): 310-315, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30820522

RESUMEN

OBJECTIVES: Memory clinics play an important role in enabling early dementia diagnosis and intervention. Few studies have investigated the changing patient profiles at memory clinics over time. We studied the trend of patient characteristics in a geriatric medicine-led memory clinic over 12 years to improve services and care to meet their needs. SETTING AND PARTICIPANTS: Data from 2340 first-visit patients seen at a memory clinic from 2005-2017 were extracted from a registered database and analysed. DESIGN: ANOVA, Pearson chi-square and non-parametric tests were used to describe and compare between patients with dementia (PWD) and patients with no dementia (PND). MEASUREMENTS: Data included diagnoses of dementia and mild cognitive impairment, age, education, MMSE scores and comorbidities. RESULTS: Patients averaged 77.2 ± 8.3 years of age with mean MMSE score of 16.2 ± 6.7. Those diagnosed with dementia were older (78.3 ± 7.9 years) and almost half (48.4%) had moderate or moderately severe dementia (FAST 5-6). Over time, there was a growing proportion of patients with mild cognitive impairment (MCI) and mild Alzheimer's dementia. Many PWD had co-morbidities of hypertension (65.9%), hyperlipidemia (55.1%), diabetes (33.5%) and 28.4% were frail. CONCLUSIONS: The findings call for services to better diagnose and manage patients at the earlier stages of cognitive impairment and provide holistic interventions for those with frailty and other co-morbidities. The continued rise in number of patients presenting to memory clinics provides impetus to expedite integration of tertiary-based memory clinics with primary and community care providers to better support PWD and their families.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Disfunción Cognitiva/complicaciones , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Disfunción Cognitiva/patología , Femenino , Humanos , Masculino , Memoria , Servicio Ambulatorio en Hospital , Factores de Tiempo
10.
Climacteric ; 22(3): 229-235, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30572743

RESUMEN

Despite pelvic organ prolapse being a universal problem experienced in nearly 50% of parous women, the surgical management of vaginal prolapse remains an enigma to many, with wide variation in the rates and types of intervention performed. As part of the 6th International Consultation on Incontinence (ICI) our committee, charged with producing an evidence-based report on the surgical management of prolapse, produced a pathway for the surgical management of prolapse. The 2017 ICI surgical management of prolapse evidence-based pathway will be presented and summarized. Weaknesses of the data and pathway will be discussed and avenues for future research proposed.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/estadística & datos numéricos , Prolapso de Órgano Pélvico/cirugía , Factores de Edad , Toma de Decisiones , Femenino , Humanos , Incidencia
11.
J Neurosci Methods ; 305: 36-45, 2018 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-29758234

RESUMEN

BACKGROUND: There is growing interest in ultra-high field magnetic resonance imaging (MRI) in cognitive and clinical neuroscience studies. However, the benefits offered by higher field strength have not been evaluated in terms of effective connectivity and dynamic causal modelling (DCM). NEW METHOD: In this study, we address the validity of DCM for 7T functional MRI data at two levels. First, we evaluate the predictive validity of DCM estimates based upon 3T and 7T in terms of reproducibility. Second, we assess improvements in the efficiency of DCM estimates at 7T, in terms of the entropy of the posterior distribution over model parameters (i.e., information gain). RESULTS: Using empirical data recorded during fist-closing movements with 3T and 7T fMRI, we found a high reproducibility of average connectivity and condition-specific changes in connectivity - as quantified by the intra-class correlation coefficient (ICC = 0.862 and 0.936, respectively). Furthermore, we found that the posterior entropy of 7T parameter estimates was substantially less than that of 3T parameter estimates; suggesting the 7T data are more informative - and furnish more efficient estimates. COMPARED WITH EXISTING METHODS: In the framework of DCM, we treated field-dependent parameters for the BOLD signal model as free parameters, to accommodate fMRI data at 3T and 7T. In addition, we made the resting blood volume fraction a free parameter, because different brain regions can differ in their vascularization. CONCLUSIONS: In this paper, we showed DCM enables one to infer changes in effective connectivity from 7T data reliably and efficiently.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Adulto , Encéfalo/fisiología , Circulación Cerebrovascular , Femenino , Mano/fisiología , Humanos , Masculino , Modelos Cardiovasculares , Modelos Neurológicos , Actividad Motora/fisiología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Oxígeno/sangre , Reproducibilidad de los Resultados , Adulto Joven
12.
Psych J ; 6(3): 175-184, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28613018

RESUMEN

The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is often used in forensic psychological/psychiatric assessment. This was a pilot study on the utility of the Chinese MMPI-2 in detecting feigned mental disorders. The sample consisted of 194 university students who were either simulators (informed or uninformed) or controls. All the participants were administered the Chinese MMPI-2 and the Structured Interview of Reported Symptoms-2 (SIRS-2). The results of the SIRS-2 were utilized to classify the participants into the feigning or control groups. The effectiveness of eight detection indices was investigated by using item analysis, multivariate analysis of covariance (MANCOVA), and receiver operating characteristic (ROC) analysis. Results indicated that informed-simulating participants with prior knowledge of mental disorders did not perform better in avoiding feigning detection than uninformed-simulating participants. In addition, the eight detection indices of the Chinese MMPI-2 were effective in discriminating participants in the feigning and control groups, and the best cut-off scores of three of the indices were higher than those obtained from the studies using the English MMPI-2. Thus, in this sample of university students, the utility of the Chinese MMPI-2 in detecting feigned mental disorders was tentatively supported, and the Chinese Infrequency Scale (ICH), a scale developed specifically for the Chinese MMPI-2, was also supported as a valid scale for validity checking.


Asunto(s)
Simulación de Enfermedad/diagnóstico , Trastornos Mentales/diagnóstico , Inventario de Personalidad , Adolescente , Adulto , Femenino , Psiquiatría Forense , Humanos , Masculino , Simulación de Enfermedad/complicaciones , Trastornos Mentales/complicaciones , Proyectos Piloto , Curva ROC , Adulto Joven
13.
Osteoarthritis Cartilage ; 24(1): 188-91, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26256767

RESUMEN

OBJECTIVE: Collagen type 2 (Col2)-Cre or tamoxifen-inducible Col2-CreER transgenic mouse lines have been used for studies to explore the cellular and molecular pathogenesis of osteoarthritis (OA). The purpose of this study is to investigate whether the targeted cells are the same or different in the two mouse lines. METHODS: We crossed tamoxifen inducible Col2-CreER and Col2-Cre mice with Rosa tdTomato reporter mice and analyzed the labeling patterns at different time points. RESULTS: In the Col2-CreER mice, 90.8 [95% confidence interval (CI) (88.3, 93.2)] and 82.8 (77.4, 88.3) % of the articular surface cells are Tomato positive when tamoxifen was administered at 2 and 2.5 weeks of age and strong activity was observed even 4.5 months after injection. However, 46.0 (32.8, 59.1) and 22.2 (11.7, 32.6) % of the surface cells were Tomato positive when tamoxifen was administered at 3 and 4 weeks of age, respectively. Little to no Tomato activity in the articular surface cells was observed when tamoxifen was administered at 8 weeks of age. At any stage of tamoxifen injection, the Tomato activity was detected in growth plate and epiphyseal bone in addition to articular chondrocytes, but little in endosteum and not in the synovium and ligament. In contrast, the targeted tissues in the Col2-Cre mouse line were articular cartilage, growth plate, meniscus, endosteum, ligament, bone and synovium. CONCLUSIONS: This study demonstrates that the pattern of targeted cells in the inducible Col2-CreER mice are partially overlapping with but different from that of targeted cells in Col2-Cre mice and the pattern varies dependent on when tamoxifen is administered.


Asunto(s)
Cartílago Articular/metabolismo , Condrocitos/metabolismo , Colágeno Tipo II/metabolismo , Placa de Crecimiento/metabolismo , Proteínas Luminiscentes/metabolismo , Rodilla de Cuadrúpedos/metabolismo , Animales , Huesos/metabolismo , Genes Reporteros , Articulación de la Rodilla/metabolismo , Ratones , Ratones Transgénicos , Tamoxifeno
14.
Mucosal Immunol ; 8(5): 1083-98, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25669151

RESUMEN

Intranasal (i.n.) vaccination generates immunity across local, regional, and distant sites. However, nasal dendritic cells (DCs), pivotal for the induction of i.n. vaccine-induced immune responses, have not been studied in detail. Here, by using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of "classical" DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were Fms-related tyrosine 3 kinase ligand responsive and displayed unique phenotypic and functional characteristics, including the ability to present antigen, induce an allogeneic T-cell response, and migrate in response to lipopolysaccharide or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1(+) DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1(+) and BDCA-3(hi) DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic, and functional properties of nasal DCs, and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis.


Asunto(s)
Células Dendríticas/citología , Células Dendríticas/inmunología , Mucosa Nasal/citología , Mucosa Nasal/inmunología , Animales , Antígenos CD1/inmunología , Antígenos de Superficie/inmunología , Proteínas de Unión al ADN/inmunología , Glicoproteínas/inmunología , Humanos , Ratones , Ratones Endogámicos BALB C , Rinitis/inmunología , Rinitis/patología , Sinusitis/inmunología , Sinusitis/patología , Trombomodulina , Factores de Transcripción/inmunología
17.
Mucosal Immunol ; 6(4): 678-91, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23168837

RESUMEN

The chemokine receptor, CCR7, directs the migration of dendritic cells (DCs) from peripheral tissue to draining lymph nodes (LNs). However, it is unknown whether all pulmonary DCs possess migratory potential. Using novel Ccr7(gfp) reporter mice, we found that Ccr7 is expressed in CD103⁺ and a CD14(med/lo) subset of CD11b(hi) classical (c)DCs but not in monocyte-derived (mo)DCs, including Ly-6C(hi)CD11b(hi) inflammatory DCs and CD14(hi)CD11b(hi) DCs. Consequently, cDCs migrated to lung-draining LNs but moDCs did not. Mice lacking the chemokine receptor, CCR2, also lacked inflammatory DCs in the lung after lipopolysaccharide inhalation but retained normal levels of migratory DCs. Conversely, the lungs of fms-like tyrosine kinase 3 ligand (Flt3L)-deficient mice lacked cDCs but retained moDCs, which were functionally mature but did not express Ccr7 and were uniformly non-migratory. Thus, the migratory properties of pulmonary DCs are determined by their developmental lineage.


Asunto(s)
Linaje de la Célula , Movimiento Celular/inmunología , Células Dendríticas/inmunología , Pulmón/inmunología , Animales , Antígenos CD/metabolismo , Antígenos Ly/metabolismo , Antígeno CD11b/metabolismo , Células Dendríticas/metabolismo , Cadenas alfa de Integrinas/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Pulmón/metabolismo , Ganglios Linfáticos/inmunología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados , Receptores CCR7/metabolismo , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/metabolismo
18.
Cell Death Differ ; 20(4): 535-45, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23238564

RESUMEN

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-ß in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Complemento C1q/metabolismo , Lectinas Tipo C/metabolismo , Receptores de Superficie Celular/metabolismo , Bazo/metabolismo , Animales , Apoptosis , Células CHO , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/genética , Células Cultivadas , Complemento C3/metabolismo , Cricetinae , Cricetulus , ADN de Cadena Simple/inmunología , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Células Jurkat , Lectinas Tipo C/antagonistas & inhibidores , Lectinas Tipo C/genética , Hígado/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Unión Proteica , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/genética , Bazo/citología , Timocitos/citología , Timocitos/metabolismo , Transfección , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
19.
J Biomech ; 42(8): 972-81, 2009 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-19380143

RESUMEN

Anterior cruciate ligament (ACL) injury is a major problem worldwide and prevails during high-impact activities. It is not well-understood how the extent and distribution of cartilage damage will arise from repetitive landing impact loads that can lead to ACL failure. This study seeks to investigate the sole effect of repetitive incremental landing impact loads on the induction of ACL failure, and extent and distribution of tibiofemoral cartilage damage in cadaveric knees. Five cadaveric knees were mounted onto a material testing system at 70 degrees flexion to simulate landing posture. A motion-capture system was used to track rotational and translational motions of the tibia and femur, respectively. Each specimen was compressed at a single 10Hz haversine to simulate landing impact. The compression trial was successively repeated with increasing actuator displacement till a significant compressive force drop was observed. All specimens underwent ACL failure, which was confirmed via magnetic resonance scans and dissection. Volume analysis, thickness measurement and histological techniques were employed to assess cartilage lesion status. For each specimen, the highest peak compressive force (1.9-7.8kN) was at the final trial in which ACL failure occurred; corresponding posterior femoral displacement (7.6-18.0mm) and internal tibial rotation (0.6 degrees -4.7 degrees ) were observed. Significant compressive force drop (79.8-90.9%) was noted upon ACL failure. Considerable cartilage deformation and damage were found in exterior, posterior and interior femoral regions with substantial volume reduction in lateral compartments. Repeated application of incremental landing impact loads can induce both ACL failure and cartilage damage, which may accelerate the risk of developing osteoarthritis.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Cartílago/fisiopatología , Fémur/fisiopatología , Articulación de la Rodilla/fisiopatología , Tibia/fisiopatología , Adulto , Cadáver , Fuerza Compresiva , Humanos , Traumatismos de la Rodilla/complicaciones , Persona de Mediana Edad , Osteoartritis/etiología
20.
Br J Radiol ; 82(979): 549-53, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19221187

RESUMEN

A decreased level of the hippocampal choline signal was found in patients with depression in previous proton magnetic resonance spectroscopy ((1)H-MRS) studies. The objective of this study is to compare choline levels before and after the forced swimming test (FST), an animal model of depression typically used for assessing antidepressant activity. (1)H-MRS spectra were obtained from both the left and right hippocampus. After the FST, rats showed a significant decrease of the choline/creatine (Cho/Cr, p = 0.037) and choline/N-acetylaspartate (Cho/NAA, p = 0.048) ratios in the left hippocampus, but not in the right hippocampus. This finding was analogous to results from patients with depression. It suggests that decreased Cho/Cr and Cho/NAA ratios in the left hippocampal regions might be considered to be biomarkers in rats with depression.


Asunto(s)
Colina/metabolismo , Trastorno Depresivo/metabolismo , Hipocampo/metabolismo , Animales , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Creatina/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Esfuerzo Físico , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/metabolismo , Natación/fisiología
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