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Liao H.-Y.,National Health Research Institute | Chung Y.-T.,National Health Research Institute | Lai C.-H.,National Defense Medical Center | Lin M.-H.,Institute of Occupational Safety and Health | And 3 more authors.
Industrial Health | Year: 2014

The aim of this study was to survey the work-relatedness of symptoms and diseases among engineered nanomaterials handling workers by questionnaire. A total of 258 exposed workers and 200 comparison workers were recruited from 14 nanomaterials handling factories in Taiwan. In addition to current disease status (prevalence), we classified the diseases worsened by employment (worsened by work). The control banding nanotool risk level matrix was adopted to categorize the severity and probability of nanomaterial exposure. The work-relatedness of symptoms was also self-reported in the questionnaire. The only symptom identified as significantly work-related was sneezing (5.88% in risk level 2 and 7.91% in risk level 1 vs. 2.00% in controls, p=0.04). The prevalences of work-related dry cough (p=0.06) and productive cough (p=0.09) in nanomaterials handling workers were also higher than those in controls. The only disease significantly worsened by work was allergic dermatitis (4.20% in risk level 2, 0% in risk level 1 vs. 0.50% in control, p=0.01). The incidence of angina in nanoworkers was also higher than in controls (p=0.06). In addition to allergic diseases, cardiopulmonary symptoms such as cough and angina may be used as screening tools for medical surveillance of people handling engineered nanomaterials. © 2014 National Institute of Occupational Safety and Health.

Wahlqvist M.L.,National Health Research Institute | Wahlqvist M.L.,National Defense Medical Center | Wahlqvist M.L.,Monash University | Lee M.-S.,National Defense Medical Center | And 6 more authors.
Parkinsonism and Related Disorders | Year: 2012

Objectives: Type 2 diabetes (T2DM) may increase the risk of Parkinson's disease (PD). We evaluated the role of oral anti-hyperglycemic agents (OAA) in any diabetes-PD linkage. Methods: From the Taiwan National Health Insurance database on 01-01-2000, a representative cohort of 800,000 was obtained between 1996-01-01 and 2007-12-31. Those ≥20 years were classified by presence (n = 64,166) or absence (n = 698,587) of T2DM, and whether any OAA (n = 41,003) or not (n = 23,163) was used. Those with T2DM were matched with those diabetes-free by birth-date and gender for the comparison of PD incidence. We considered those ≥50 years and matched PD-free diabetes patients with and without OAAs by age, gender, locality, health service, Charlson comorbidity index and T2DM diagnosis-date to avoid 'immortal time bias'. PD incidence densities (PID, per 10,000 person-years) and hazard ratios (HRs) were calculated. Results: HRs (95% confidence interval, CI), related to diabetes-free, were 2.18 (1.27-3.73) and 1.30 (0.77-2.19) for T2DM without and with OAAs. For sulfonylurea alone, PID (95% CI) increased from 58.3 (46.6-70.1) to 83.2 (68.6-97.7), with similar findings by gender, but little difference if metformin was used. The metformin-alone HR (95% CI) was 0.95 (0.53-1.71), sulfonylurea-alone 1.57 (1.15-2.13), and combined therapy 0.78 (0.61-1.01) and these differences persisted when incident PD was excluded for 4 years after T2DM diagnosis. The use of metformin first, in those without insulin, provided an HR of 0.40 (0.17-0.94). Conclusions: Incident PD risk in T2DM increases 2.2-fold. Sulfonylureas further increase risk by 57%, which is avoided by combination with metformin. © 2012 Elsevier Ltd.

Hsu C.-C.,National Health Research Institute | Hsu C.-C.,China Medical University and Hospital | Wahlqvist M.L.,National Health Research Institute | Wahlqvist M.L.,National Defense Medical Center | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2011

To determine incidence of dementia in type 2 diabetic (T2DM) patients, and whether there are adverse or favorable effects of oral agents (OA) in DM, we obtained a representative cohort of 800,000 from Taiwan's National Health Insurance database. Those who, as of on January 1, 2000, were 50 years or older and dementia free (n = 127,209) were followed until December 31, 2007, in relation to absence (n = 101,816) or presence (n = 25,393) of T2DM, and whether any OA was used. Dementia was ascertained by ICD9-CM or A-code. Dementia incidence densities (DID) and fully adjusted Cox proportional hazard models were used to estimate association between dementia, DM, and OA. Notably, DID (per 10,000 person-years) was markedly increased with DM (without medication), compared to DM free subjects (119 versus 46). Using non-DM as reference, the adjusted hazard ratios (HRs) (95% confidence interval) for DM without and with OA were 2.41 (2.17-2.66) and 1.62 (1.49-1.77), respectively. For T2DM, compared with no medication, sulfonylureas alone reduced the HR from 1 to 0.85 (0.71-1.01), metformin alone to 0.76 (0.58-0.98), while with combined oral therapy the HR was 0.65 (0.56-0.74). Adjustments included cerebrovascular diseases so that non-stroke related dementias were found to be decreased in DM with sulfonylurea and metformin therapy. T2DM increases the risk of dementia more than 2-fold. On the other hand, sulfonylureas may decrease the risk of dementia, as does metformin; together, these 2 OAs decrease the risk of dementia in T2DM patients by 35% over 8 years. © 2011 IOS Press and the authors. All rights reserved.

Chan T.-M.,China Medical University at Taichung | Chan T.-M.,Everfront Biotech Inc | Chen J.Y.-R.,Guang Li Biomedicine Inc. | Ho L.-I.,Taipei Veterans General Hospital | And 14 more authors.
Cell Transplantation | Year: 2014

Neurodegenerative disorders, chronic diseases that can severely affect the patient's daily life, include amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's diseases. However, these diseases all have the common characteristic that they are due to degenerative irreversibility, and thus no efficient drugs or therapy methods can mitigate symptoms completely. Stem cell therapy, such as adipose tissue-derived stem cells (ADSCs), is a promising treatment for incurable disorders. In this review, we summarized the previous studies using ADSCs to treat neurodegenerative disorders, as well as their therapeutic mechanisms. We also suggested possible expectations for future human clinical trials involving minimized intracerebroventricular combined with intravenous administration, using different cell lineages to finish complementary therapy as well as change the extracellular matrix to create a homing niche. Depending on successful experiments in relevant neurodegenerative disorders models, this could form the theoretical basis for future human clinical trials. © 2014 Cognizant Comm. Corp.

Chen C.-Y.,Chang Gung University | Jan C.-I.,China Medical University and Hospital | Jan C.-I.,China Medical University at Taichung | Lo J.-F.,National Yang Ming University | And 8 more authors.
Cancer Research | Year: 2013

Tid1 (DNAJA3), a DnaJ cochaperone, may promote degradation of oncogenic kinases. Tid1 has 2 isoforms, Tid1-L and Tid1-S, that may function differently. In this study, we investigated the role of the Tid1 isoforms in regulating EGF receptor (EGFR) signaling and lung cancer progression. We found that both Tid1-L and Tid1-S expressions were reduced in patients with non-small cell lung cancer compared with normal counterparts. Tid1-L expression correlated inversely with EGFR expression. Low Tid1-L/high EGFR expression predicted poor overall survival in patients with lung adenocarcinoma. Tid1-L overexpression in lung cancer cells attenuated EGFR signaling and inhibited cell proliferation, colony formation, and tumor growth in subcutaneous and orthotropic xenograft models. Conversely, depletion of Tid1 restored EGFR signaling and increased cell proliferation and colony formation. Tid1-L, but not Tid1-S, interacted with EGFR/HSP70/HSP90 through the DnaJ domain, counteracting the EGFR regulatory function of HSP90 by causing EGFR ubiquitinylation and proteasomal degradation. Tid1-L inhibited EGFR signaling even more than the HSP90 inhibitor 17-allylaminodemethoxy geldanamycin. We concluded that Tid1-L acted as a tumor suppressor by inhibiting EGFR signaling through interaction with EGFR/HSP70/HSP90 and enhancing EGFR ubiquitinylation and degradation. © 2013 American Association for Cancer Research.

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