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Background Narrative medicine (NM) is an approach involving narrative skills and is regarded as a model for medical humanism and effective medical practice. This study aims to explore how NM impacts medical trainees’ learning of professionalism during a clerkship in a Taiwanese clinical setting. Methods A qualitative interview study adopting a purposive sampling method was undertaken. Thirty medical trainees participated in this study, including five fifth-year medical students (MSs), ten sixth-year MSs, nine seventh-year MSs, and six postgraduate year (PGY) trainees. Thematic framework analysis was applied, and a modified realist evaluation approach was further used to analyse the interview data. Results We identified self-exploration, reflection, and awareness of professional identity as mechanisms explaining how NM impacted professionalism learning in our participants. Furthermore, empathy, communication, doctor-patient relationship and understanding patients were identified as the outcomes of the NM intervention for trainees’ learning of professionalism. Conclusions NM facilitates medical trainees’ self-exploration, reflection, and awareness of professional identity, thereby affecting their learning of professionalism in clinical settings. Adopting NM as an educational intervention in undergraduate medical education could play an important role in professionalism learning, as trainees can thereby be supported to gradually develop self-exploration and reflection capabilities and heightened awareness of professional identity reflectively through a narrative process.

Background: Medical schools prepare undergraduates for clinical practice. Clinical competencies build up gradually and continuously. Existing literature suggests that new graduates are often unprepared for independent practice. This study aims to validate a Chinese version of a Preparedness for Hospital Practice Questionnaire (PHPQ) in a Taiwanese undergraduate cohort. Methods: The original eight-domain English version PHPQ was translated into Chinese and back-translated for expert panel discussion. The eight domains encompass interpersonal skills, confidence, collaboration, management, science, prevention, holistic care, and self-directed learning. Reliability and validity were checked by Cronbach's alpha and by confirmatory factor analysis (CFA), respectively. Participants were divided into higher and lower preparedness groups according to PHPQ results, and compared by age, sex, professional identity, and perception of educational environment. Results: A total of 129 undergraduate medical students (55% males) participated in the study. The overall Cronbach's alpha was 0.94. Participants were found to be best prepared in the domain of disease prevention (M = 4.37, SD = 0.68) and least prepared in interpersonal skills (M = 2.68, SD = 0.77). A satisfactory goodness of fit data was yield from CFA with a CMIN/DF of 2.02. Higher levels of preparedness are associated with stronger professional identity (p

Background Reflection and various approaches to foster reflection have been regarded as an indispensable element in enhancing professional practice across different disciplines. With its inherent potential to engage learners in reflection and improvement, narrative medicine has been adopted in various settings. However, the relevance and effectiveness of reflection remains underexplored in the context of narrative medicine, specifically in regard to the concern about variability of learner acceptance and the way learners really make sense of these reflective activities. This study aimed to explore what medical learners experience through narrative medicine and the meanings they ascribe to the phenomenon of this narrative-based learning. Methods Using a transcendental phenomenology approach, twenty medical learners were interviewed about their lived experiences of taking a narrative medicine course during their internal medicine clerkship rotation. Moustakas’ phenomenological analysis procedures were applied to review the interview data. Results Six themes were identified: feeling hesitation, seeking guidance, shifting roles in narratives, questioning relationships, experiencing transformation, and requesting a safe learning environment. These themes shaped the essence of the phenomenon and illustrated what and how medical learners set out on a reflective journey in narrative medicine. These findings elucidate fundamental elements for educators to consider how narrative approaches can be effectively used to engage learners in reflective learning and practice. Conclusion Adopting Moustakas’ transcendental phenomenology approach, a better understanding about the lived experiences of medical learners regarding learning in narrative medicine was identified. Learner hesitancy should be tackled with care by educators so as to support learners with strategies that address guidance, relationship, and learning environment. In so doing, medical learners can be facilitated to develop reflective capabilities for professional and personal growth.

Background Active learning is defined as any instructional method that engages students in the learning process. Cultural differences in learning patterns can play an important role in engagement with active learning. We aimed to examine process models of active learning to understand what works, for whom and why. Methods Forty-eight sixth- and seventh-year medical students with experience of active learning methods were purposively selected to participate in ten group interviews. Interactions around active learning were analysed using a realist evaluation framework to unpack the ‘context-mechanism-outcome’ (CMO) configurations. Results Three core CMO configurations, including cultural, training and individual domains, were identified. In the cultural context of a strong hierarchical culture, the mechanisms of fear prompted students to be silent (outcome) and dare not give their opinions. In the training context of teacher-student familiarity alongside teachers’ guidance, the mechanisms of learning motivation, self-regulation and enthusiasm were triggered, prompting positive learning outcomes and competencies (outcome). In the individual context of learning how to learn actively at an early stage within the medical learning environment, the mechanisms of internalisation, professional identity and stress resulted in recognising active learning and advanced preparation (outcomes). Conclusions We identified three CMO configurations of Taiwanese medical students’ active learning. The connections among hierarchical culture, fear, teachers’ guidance, motivation, the medical environment and professional identity have been shown to affect the complex interactions of learning outcomes. Fear derived from a hierarchical culture is a concern as it is a significant and specific contextual factor, often sparking fear with negative outcomes.

BackgroundActive learning is defined as any instructional method that engages students in the learning process. Cultural differences in learning patterns can play an important role in engagement with active learning. We aimed to examine process models of active learning to understand what works, for whom and why.MethodsForty-eight sixth- and seventh-year medical students with experience of active learning methods were purposively selected to participate in ten group interviews. Interactions around active learning were analysed using a realist evaluation framework to unpack the ‘context-mechanism-outcome’ (CMO) configurations.ResultsThree core CMO configurations including cultural, training and individual domains were identified. In the cultural context of a strong hierarchical culture, the mechanisms of fear prompted students to be silent (outcome), daring not to share their opinions. In the training context of teacher-student familiarity alongside teachers’ guidance, the mechanisms of learning motivation, self-regulation and enthusiasm are triggered, prompting positive learning outcomes and competencies (outcome). In the individual context of learning how to learn actively at an early stage within the medical learning environment, the mechanisms of internalisation, professional identity and stress, resulted in recognised active learning and advanced preparation (outcomes).ConclusionsWe identified three CMO configurations of Taiwanese medical students’ active learning. The connections between hierarchical culture, fear, teachers’ guidance, motivation, the medical environment and professional identity have been shown to affect the complex interactions of learning outcomes. Fear derived from a hierarchical culture is a concern as it is a significant and specific contextual factor, often sparking fear with negative outcomes.

Background Western medicine is an evidence-based science, whereas Chinese medicine is more of a healing art. To date, there has been no research that has examined whether students of Western and Chinese medicine differentially engage in, or benefit from, educational activities for narrative medicine. This study fills a gap in current literature with the aim of evaluating and comparing Western and Chinese Medicine students’ perceptions of narrative medicine as an approach to learning empathy and professionalism. Methods An initial 10-item questionnaire with a 5-point Likert scale was developed to assess fifth-year Western medical (MS) and traditional Chinese medical (TCMS) students’ perceptions of a 4-activity narrative medicine program during a 13-week internal medicine clerkship. Exploratory factor analysis was undertaken. Results The response rate was 88.6% (412/465), including 270 (65.5%) MSs and 142 (34.5%) TCMSs, with a large reliability (Cronbach alpha = 0.934). Three factors were extracted from 9 items: personal attitude, self-development/reflection, and emotional benefit, more favorable in terms of enhancement of self-development/reflection. The perceptions of narrative medicine by scores between the two groups were significantly higher in TCMSs than MSs in all 9-item questionnaire and 3 extracted factors. Conclusions Given the different learning cultures of medical education in which these student groups engage, this suggests that undertaking a course in Chinese medicine might enhance one’s acceptance to, and benefit from, a medical humanities course. Alternatively, Chinese medicine programmes might attract more humanities-focused students.

Shu-Chuan Ho,1,2 Jiun-Yi Wang,3,4 Han-Pin Kuo,5 Chien-Da Huang,5 Kang-Yun Lee,2,6 Hsiao-Chi Chuang,1,2 Po-Hao Feng,2,6 Tzu-Tao Chen,2,* Min-Fang Hsu7,* 1School of Respiratory Therapy, College of Medicine, 2Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 3Department of Healthcare Administration, Asia University, Wufeng, 4Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 5Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 6Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, 7Department of Nursing, Yuanpei University of Medical Technology, Hsinchu City, Taiwan *These authors contributed equally to this work Background: Chronic obstructive pulmonary disease (COPD) is currently the third most common cause of death in the world. Patients with COPD experience airflow obstruction, weight loss, skeletal muscle dysfunction, and comorbidities. Anthropometric indicators are risk factors for mortality in geriatric assessment. Purpose: This study examined and compared the associations of anthropometric indicators, such as low body mass index (BMI), low mid-arm circumference (MAC), and low calf circumference (CC), with the prediction of a 3-year follow-up mortality risk in patients with COPD. Methods: We recruited nonhospitalized patients with COPD without acute conditions from a general hospital in Taiwan. The BMI, MAC, and CC of all patients were measured, and they were followed for 3 years through telephone interviews and chart reviews. The Kaplan–Meier survival curves stratified by BMI, MAC, and CC were analyzed. Variables univariately associated with survival were entered into a multivariate Cox regression model. The Bayesian information criterion was used to compare the predictive ability of the three anthropometric indicators to predict mortality rate. Results: In total, 104 patients were included (mean ± standard deviation age, 74.2±6.9 years; forced expiratory volume in 1 second [%], 58.4±20.4 predicted; males, 94.2%); 22 patients (21.2%) died during the 36-month follow-up. During this long-term follow-up, the three anthropometric indicators could predict mortality risk in patients with COPD (low BMI [

This study reports a biomimetic microsystem that reconstitutes the lung microenvironment for monitoring the role of eosinophil cationic protein (ECP) in lung inflammation. ECP induces the airway epithelial cell expression of CXCL-12, which in turn stimulates the migration of fibrocytes towards the epithelium. This two-layered microfluidic system provides a feasible platform for perfusion culture, and was used in this study to reveal that the CXCL12-CXCR4 axis mediates ECP induced fibrocyte extravasation in lung inflammation. This 'lung-on-a-chip' microdevice serves as a dynamic transwell system by introducing a flow that can reconstitute the blood vessel-tissue interface for in vitro assays, enhancing pre-clinical studies. We made an attempt to develop a new microfluidic model which could not only simulate the transwell for studying cell migration, but could also study the migration in the presence of a flow mimicking the physiological conditions in the body. As blood vessels are the integral part of our body, this model gives an opportunity to study more realistic in vitro models of organs where the blood vessel i.e. flow based migration is involved.

Background The cultivation of empathy for healthcare providers is an important issue in medical education. Narrative medicine (NM) has been shown to foster empathy. To our knowledge, there has been no research that examines whether a NM programme affects multi-professional healthcare providers’ empathy. Our study aims to fill this gap by investigating whether a NM programme effects multi-professional healthcare providers’ empathy. Methods A pre-post questionnaire method was used.142 participants (n = 122 females) who attended the NM programme were divided into single (n = 58) and team groups (n = 84) on the basis of inter-professional education during a period of 2 months. Perceptions of the NM programme were collected using our developed questionnaire. Empathy levels were measured using the Chinese version of Jefferson Scale of Empathy - Healthcare Providers Version (JSE-HP) – at three time points: prior to (Time 1), immediately after (T2), and 1.5 years (T3) after the programme. Results Participants’ perceptions about the NM programme (n = 116; n = 96 females) suggested an in enhancement of empathy (90.5%). Empathy scores via the JSE-HP increased after the NM programme (T1 mean 111.05, T2 mean 116.19) and were sustainable for 1.5 years (T3 mean 116.04) for all participants (F(2297) = 3.74, p

Although the prevalence of both obstructive sleep apnoea (OSA) and asthma are both increasing, little is known about the impact of OSA on the natural history of lung function in asthmatic patients. A total of 466 patients from our sleep laboratory were retrospectively enrolled. Of them, 77 patients (16.5%) had asthma with regular follow-up for more than 5 years. Their clinical characteristics, pulmonary function, emergency room visits, and results of polysomnography results were analysed. The patients were divided into three groups according to the severity of the apnoea-hypopnea index (AHI). The decline in FEV1 among asthma patients with severe OSA (AHI > 30/h) was 72.4 ± 61.7 ml/year (N = 34), as compared to 41.9 ± 45.3 ml/year (N = 33, P = 0.020) in those with mild to moderate OSA (5

α–smooth muscle actin-positive cells also express both collagen I and CD45. NANT cells from one healthy subject were harvested after 3 days in culture and stained with antibodies for collagen I (Col I), α- smooth muscle actin (SMA) and CD45 or their respective IgG isotype controls. (A and C). The percentage of Col I+/α-SMA+ (B) and CD45+/ α-SMA+ cells (D) was determined by flow cytometry. (PDF 112 kb)

Effect of ICI-118,551 on salmeterol-mediated reduction in fibrocyte number and differentiation. NANT cells from healthy subjects (n = 6) were treated with salmeterol (10−8 M) in the presence or absence of ICI-118,551 (10−5 M) for 3 days. The number of fibrocytes (Col I+/CD45+ cells; A) and differentiating fibrocytes (α-SMA+ cells; B) was determined. Bars represent mean ± SEM.* p

English version of questionnaire for narrative medicine. Participants’ perceptions about narrative medicine for Table S1. The results show that participants’ perceptions were positive (strongly agree and agree) in terms of enhancement of reflection (106/116, 91.4%), empathy (105/116, 90.5%), and patient-doctor relationships (98/116, 84.5%). (DOC 48 kb)

Number of fibrocytes and differentiating fibrocytes in NANT cells after culture in the absence or presence of salmeterol. The number of fibrocytes (% Col I+/CD45+; A) and differentiating fibrocytes (% α-SMA+; B) within the NANT cell population, were determined in the NANT cells from healthy subjects (n = 8–9) and patients with non-severe (n = 7) or severe asthma (n = 7–9) at day 0 (0 d) or after 3 days (3 d) in the absence or presence of salmeterol (10−9- 10−7 M). Data points represent mean ± SEM. * p

Background: Modification of human airway smooth muscle (ASM) function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM)-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPAR)γ reportedly possess anti-inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARγ ligand, can modulate the basal and tumor necrosis factor (TNF)α-induced ICAM1 gene expression in human ASM cells. Methods: Human ASM cells were treated with TNFα. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. PPARγ activity was inhibited by target-specific small interfering (si) RNA targeting PPARγ and GW9662, a PPARγ antagonist. Activity of nuclear factor (NF)-κB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA). Results: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFα (10 ng/ml) in a dose-dependent manner (1-10 μM). It also inhibited TNFα-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPAR γ gene by target-specific siRNA targeting PPAR γ enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFα-induced ICAM-1 expression was reversed by PPARγ siRNA and GW9662. SN-50 (10 μg/ml), an inhibitor for nuclear translocation of NF-κB, inhibited TNFα-induced ICAM-1 expression. Ciglitazone did not prevent TNFα-induced degradation of the cytosolic inhibitor of NF-κB (IκB), but inhibited the nuclear translocation of p65 induced by TNFα and suppressed the NF-κB/DNA binding activity. Conclusion: These findings suggest that ciglitazone inhibits TNFα-induced ICAM1 gene expression in human ASM cells through the ligand-dependent PPARγ activation and NF-κB-dependent pathway.

Rationale: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T-cell immunity in tumor-bearing hosts. Their clinical relevance remains unclear.Objectives: To identify subtypes of myeloid-derived suppressor cells in patients with non–small cell lung cancer (NSCLC) and their clinical relevance.Methods: CD11b+CD14− and CD11b+CD14+ cells, determined and phenotyped by fluorescence-activated cell sorter analysis, in the peripheral blood mononuclear cells (PBMCs) of treatment-naive patients with advanced NSCLC were correlated with clinical data. T-cell activation in response to CD3/CD28 costimulation was determined by carboxy-fluorescein diacetate succinimidyl ester (CFSE) staining and ELISA analysis of IFN-γ. The percentage of CD11b+CD14+S100A9+ cells in PBMCs was correlated with and tested as a predictor for treatment response in a cohort of patients prospectively receiving first-line cisplatin-based chemotherapy.Measurements and Main Results: Patients with NSCLC...

Background Although the prevalence of both obstructive sleep apnoea (OSA) and asthma are both increasing, little is known about the impact of OSA on the natural history of lung function in asthmatic patients. Methods A total of 466 patients from our sleep laboratory were retrospectively enrolled. Of them, 77 patients (16.5%) had asthma with regular follow-up for more than 5 years. Their clinical characteristics, pulmonary function, emergency room visits, and results of polysomnography results were analysed. Results The patients were divided into three groups according to the severity of the apnoea-hypopnea index (AHI). The decline in FEV1 among asthma patients with severe OSA (AHI > 30/h) was 72.4 ± 61.7 ml/year (N = 34), as compared to 41.9 ± 45.3 ml/year (N = 33, P = 0.020) in those with mild to moderate OSA (5

Due to the pressure of modern life and work, resulting in poor quality of sleep, insomnia and other issues, in order to find suitable for daily life can get sleep quality approach to further analysis to improve sleep quality. This paper contained a Bluetooth device through a single conductive layer measured by EEG brainwave of slow-wave signals to judge the quality of sleep during sleep. This paper use wearable module DAQ100 to measure the sleep cycle α, β, θ, δ four single conductive layer, and transmit this date to the cloud to do data analysis by Bluetooth device, to improve the sleep quality.

Modern life is more busy than previous, after a busy day of work, sleep quality at night has become an important part of the next day that can working smoothly. With the development of wearable devices, people must go to the medical center to spend a whole day for sleep diagnosis in the past day, but now they have opportunity achieve a simple sleep quality measurement by using wearable devices.

Background Fibrocytes are circulating progenitor cells that are increased in asthmatic patients with chronic obstructive asthma (COA) and rapid decrease in lung function. Fibrocytes from patients with COA have a greater capacity for proliferation and differentiation. Objective We investigated whether epidermal growth factor receptor (EGFR) activation mediated the proliferation of fibrocytes in patients with COA and whether oxidative stress was involved in this activation. Methods Circulating fibrocytes from nonadherent non–T-cell mononuclear cell fractions from healthy subjects, asthmatic patients with normal pulmonary function, and patients with COA were determined by using flow cytometric coexpression of collagen I, CD45, and CD34 or EGFR or a disintegrin and metalloprotease domain 17 and placed in culture. Results Expression of EGFR was increased in fibrocytes from patients with COA compared with that seen in patients with NPF. AG1478 and gefitinib, inhibitors of EGFR tyrosine kinase, reduced fibrocyte proliferation and myofibroblast transformation. Increased expression of EGFR and fibrocyte proliferation and transformation were induced by hydrogen peroxide, and these effects were inhibited by N-acetylcysteine. Conclusions Enhanced fibrocyte proliferation and transformation found in patients with COA might be mediated through an oxidant-sensitive EGFR-dependent pathway.

Introduction Infection is a frequent cause of death in patients with systemic lupus erythematous (SLE) admitted to the intensive care unit (ICU). Complicated clinical features of SLE patients may delay or cause inadequate antimicrobial treatment. This study aimed to determine if inadequate antimicrobial treatment is an independent risk factor for mortality in SLE patients in the ICU. Methods Fifty-eight SLE patients admitted to the ICU were evaluated in a retrospective analysis. Inadequate antimicrobial treatment was defined by patient receiving antibiotics ≥24hours after the diagnostic criteria for nosocomial infection and/or the identified microorganism did not exhibit in vitro sensitivity to the antibiotics administered in the ICU. Results Multivariate logistic regression analysis identified the risk factors. Thirty-three (56.9%) SLE patients died during their ICU stay. The nonsurvivor group (n=33), exhibited lower platelet count ( P =0.025), prolonged hospital stay before ICU admission ( P =0.015), higher Acute Physiology and Chronic Health Evaluation II score ( P =0.015), and higher prevalence of multiple organ failure ( P =0.044) and inadequate antimicrobial treatment ( P =0.002) compared with the survivor group (n=25). In multivariate logistic regression analysis, inadequate antimicrobial treatment was the most significant factor for mortality (odds ratio=12.02, 95% confidence interval=1.24–116.10, P =0.032). Patients with prolonged hospitalization prior ICU admission had a mild risk for mortality (odds ratio=1.06, 95% confidence interval=1.00–1.12, P =0.045). Conclusions SLE patients in the ICU receiving inadequate antimicrobial treatment or with prior prolonged hospital stay have a higher risk of mortality. Clinical efforts should ensure adequate antimicrobial treatment in SLE patients with prior prolonged hospital stay before ICU admission.

Objective This retrospective study was to determine factors that contribute to self-expandable metallic stent fracture in patients with tracheobronchial disease. Methods From 2001 to 2006, 139 patients (age, 62.1 ± 15.4 years; range, 23–87 years) with benign (n = 62) and malignant (n = 77) tracheobronchial disease received 192 Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents (98 in patients with benign disease and 94 in patients with malignant disease). Results Seventeen fractured self-expandable metallic stents were found; the incidence was 12.2% (17/139 patients) among patients with tracheobronchial disease. Tortuous airway (odds ratio, 4.06; 95% confidence interval, 1.04–18.34; P = .04) independently predicted self-expandable metallic stent fracture. Most self-expandable metallic stent fractures (64.7%, 11/17) were detected 500 to 1000 days after self-expandable metallic stent implantation. Clinical presentations for patients with fractured self-expandable metallic stents included dyspnea exacerbation (70.6%, 12/17) and cough (23.5%, 4/17). Conclusions Self-expandable metallic stent fracture is not uncommon in patients with tracheobronchial disease. Tortuous airway is an independent predictor for it. Although management of the fractured self-expandable metallic stent in our study was feasible and safe, self-expandable metallic stents should be restricted to a more select population.

A proportion of patients with asthma present with chronic airflow obstruction (CAO). We hypothesized that this effect may result from increased activity of circulating fibroblast-like progenitor cells (fibrocytes) that could home to the airway mucosal wall.To compare the proportion, proliferation, and differentiation of circulating fibrocytes from patients with asthma with CAO or no airflow obstruction (NOA) and control subjects.We investigated circulating fibrocytes in 11 patients with asthma with CAO and a rapid decline in FEV(1), 9 patients with asthma with NOA, and 10 nonasthmatic control subjects. Blood nonadherent non-T (NANT) cells were incubated with fetal calf serum or each patient's own serum and fibrocytes expressing CD34, CD45, and collagen I with alpha-smooth muscle actin were identified by flow cytometry.A higher percentage of circulating fibrocytes in NANT cells was found in patients with CAO when compared with patients with NOA and control subjects. In CAO, the slope of the yearly decline in FEV(1) correlated with circulating fibrocytes (r = -0.756, n = 11, P0.01). When NANT cells from patients with CAO were cultured in the patients' own sera, more fibrocytes were detected than when cultured in sera from patients with NOA or from normal subjects. An anti-transforming growth factor (TGF)-beta(1)-neutralizing antibody inhibited alpha-smooth muscle actin-positive fibrocyte transformation from NANT cells of patients with CAO. Serum TGF-beta(1) levels were higher in patients with CAO than in patients with NOA or in normal subjects.Circulating fibrocytes are increased in patients with asthma with CAO and can be transformed by TGF-beta(1) to myofibroblasts. Fibrocytes may contribute to airway obstruction in asthma.

Summary Endobronchial tuberculosis (TB) often leads to some degree of tracheobronchial stenosis. Because matrix metalloproteinases (MMPs) play an essential role in tissue remodeling in the airways, we investigated the role of MMP-1 polymorphism in patients with endobronchial TB. One hundred and one cases of pulmonary TB in Taiwanese patients were genotyped for the 1G/2G polymorphism of MMP-1 promoter (−1607bp). Bronchoscopic examination was performed to determine the presence of endobronchial involvement. Levels of MMP-1 in peripheral blood monocytes and in bronchial biopsies were also determined. 1G genotypes of MMP-1 polymorphism, containing at least one 1G allele, were associated with the presence of endobronchial TB. Using multivariate analysis, 1G genotypes and female gender were independent predictors of the development of endobronchial TB. Endobronchial TB patients with 1G genotypes had a 9.86-fold greater risk of developing tracheobronchial stenosis. IL-1 β increased levels of MMP-1 in peripheral blood monocytes of TB patients with 1G genotypes. MMP-1 activity was also present in the endobronchial TB granuloma from patients with 1G/1G genotype. 1G genotypes of MMP-1 polymorphism were associated with a greater risk of developing tracheobronchial stenosis through up-regulation of MMP-1 activity.

Wen-Te Liu,1,2,* Han-Pin Kuo,3,* Tien-Hua Liao,4 Ling-Ling Chiang,1 Li-Fei Chen,3 Min-Fang Hsu,5 Hsiao-Chi Chuang,1 Kang-Yun Lee,2,6 Chien-Da Huang,3 Shu-Chuan Ho11School of Respiratory Therapy, College of Medicine, Taipei Medical University, 2Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, 3Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 4Department of Respiratory Therapy, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, 5Department of Healthcare Administration, Asia University, Wufeng, Taichung, 6Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan*These authors contributed equally tothis workAbstract: COPD patients have an increased prevalence of osteoporosis (OP) compared with healthy people. Physical inactivity in COPD patients is a crucial risk factor for OP; the COPD assessment test (CAT) is the newest assessment tool for the health status and daily activities of COPD patients. This study investigated the relationship among daily physical activity (DPA), CAT scores, and bone mineral density (BMD) in COPD patients with or without OP. This study included 30 participants. Ambulatory DPA was measured using actigraphy and oxygen saturation by using a pulse oximeter. BMD was measured using dual-energy X-ray absorptiometry. OP was defined as a T-score (standard deviations from a young, sex-specific reference mean BMD) less than or equal to -2.5 SD for the lumbar spine, total hip, and femoral neck. We quantified oxygen desaturation during DPA by using a desaturation index and recorded all DPA, except during sleep. COPD patients with OP had lower DPA and higher CAT scores than those of patients without OP. DPA was significantly positively correlated with (lumbar spine, total hip, and femoral neck) BMD (r=0.399, 0.602, 0.438, respectively, all P

Using thapsigargin (Tg), an agent that mobilizes calcium by directly emptying intracellular stores, we previously showed that intracellular calcium may play an important role in the regulation of intercellular adhesion molecule (ICAM)-1 gene expression induced by cytokines in human airway smooth muscle (ASM) cells. In the present study, we extended this previous observation by comparing the effect of Tg and other calcium-mobilizing G-protein-coupled receptor (GPCR) agonists on the expression of different pro-inflammatory genes in response to tumor necrosis factor (TNF)-alpha in ASM cells. We found that in resting cells, Tg (10-100 nM) or the bradykinin (BK) (1-10 muM) and thrombin (Thr) (1 U/ml) stimulated interleukin (IL)-6 secretion but had no effect on regulated on activation, normal T cells expressed and secreted (RANTES) levels. More importantly, such calcium-mobilizing agents significantly enhanced TNF-alpha-induced IL-6 secretion while RANTES secretion was abrogated. The use of luciferase-tagged IL-6 and RANTES promoter constructs demonstrated similar effects of Tg on IL-6 and RANTES genes in basal and TNF-alpha-stimulated conditions. The cyclic adenosine monophosphate (cAMP)-dependent pathway plays a minor role in this differential regulation of IL-6 and RANTES genes expression. 2-Aminoethoxydiphenyl borate (APB), a blocker of store-operated calcium channels (SOCs), and bisindolylmaleimide I (Bis I), a broad-spectrum protein kinase C (PKC) inhibitor, inhibited the basal and synergic effects of IL-6 secretion in response to calcium-mobilizing agents and TNF-alpha, but did not prevent the abrogated effect of RANTES secretion. We also found that Go-6976, a selective calcium-dependent PKC isozyme inhibitor, did not inhibit IL-6 secretion in response to GPCR agonist and TNF-alpha; whereas Rottlerlin, a PKC-delta inhibitor, inhibited both Thr- and TNF-alpha-induced expression of IL-6, while BK-induced IL-6 secretion was not affected. Interestingly, TNF-alpha-induced interferon regulatory factor (IRF)-1 activation was significantly inhibited by all calcium-mobilizing agents, BK, Thr and Tg. These results show that calcium-mobilizing GPCR agonists functionally interact with TNF-alpha to differentially regulate pro-inflammatory genes expression in human ASM cells, possibly by involving Tg-sensitive intracellular calcium stores, SOC and PKC.

Interleukin (IL)-5 plays an important role in maintaining the survival of eosinophils via the specific alpha-subunit of its receptor. Apoptosis, a form of programmed cell death, is thought to represent a mechanism that promotes the resolution of eosinophilic inflammation in asthma. The aim of our present study is to investigate whether IL-5 acts in an autocrine fashion on eosinophil apoptosis in asthmatics. Immunoreactivities of intracellular IL-5 and IL-5 receptor alpha-subunit (Ralpha) were detected uniquely on the eosinophils. The magnitude of IL-5 and IL-5 Ralpha expression on eosinophils was significantly higher in asthmatics than that of normal subjects (p0.05) determined by flow cytometry. Apoptosis of eosinophils was measured by the propidium iodide staining method and DNA ladder. The percent of apoptotic eosinophils from asthmatics was significantly increased by coincubation with anti-hIL-5 Ralpha Ab (0.1, 0.5, and 2.5 microg/mL) for 1, 2, or 16 hours than was those of corresponding controls (p0.05, n=8). However, there was no significant effect of anti-hIL-5 Ralpha Ab on eosinophil apoptosis in normal subjects. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2) proteins was significantly inhibited by the anti-hIL-5 Ralpha Ab or antisense IL-5 oligonucleotides in asthmatics (p0.05, n=8), but there was no significant change in eosinophils from normal subjects. This study demonstrates that eosinophils from asthmatics release IL-5 in an autocrine fashion to act on their own IL-5 receptors in prevention of apoptosis through the upregulation of Bcl-2 expression.

To revalidate a means of assessing delirium in intensive care unit patients and to investigate the independent effect of delirium on the mortality of mechanically ventilated patients.A prospective cohort study.A 37-bed medical intensive care unit of a tertiary care hospital.Subjects were 102 of 131 consecutive mechanically ventilated patients.All the enrolled patients were assessed for delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Mortality rate were compared between patients with or without delirium, and the predictors of death were investigated.The two CAM-ICU assessors' sensitivities in diagnosing delirium compared with reference standard were 91% and 95%, whereas their specificities were both 98%. They also demonstrated high interrater reliability with kappa statistics of 0.91. Delirium was present in 22 of 102 (22%) patients in the first 5 days. The delirious patients had higher intensive care unit mortality rate than nondelirious patients (63.6% vs. 32.5%, respectively), with a hazard ratio of 2.57 (95% confidence interval, 1.56-8.15). In multivariate analysis, delirium (odds ratio, 13.0; 95% confidence interval, 2.69-62.91), shock (odds ratio, 12.91; 95% confidence interval, 2.93-56.92), and illness severity (odds ratio, 9.61; 95% confidence interval, 2.24-41.18) were independent predictors of mortality.This study confirms previous work showing that delirium is an independent predictor for increased mortality among mechanically ventilated patients.