To explore environmental risk factors for Parkinson's disease (PD) in Taiwan, we investigated 120 patients with PD and 240 hospital control subjects matched with patients on age (+/-2 years) and sex. Based on a structured open-ended questionnaire, we carried out standardized interviews to obtain history of exposure to environmental factors, including place of residence, source of drinking water, and environmental and occupational exposures to various agricultural chemicals. In the univariate analysis, the history of living in a rural environment, farming, use of herbicides/pesticides, and use of paraquat were associated with an increased PD risk in a dose-response relationship. After adjustment for multiple risk factors through conditional logistic regression, the biological gradient between PD and previous uses of herbicides/pesticides and paraquat remained significant. The PD risk was greater among subjects who had used paraquat and other herbicides/pesticides than those who had used herbicides/pesticides other than paraquat. There were no significant differences in occupational exposures to chemicals, heavy metals, and minerals between PD patients and matched control subjects. The duration of drinking well water and alcohol consumption was not significantly associated with PD. There was an inverse relationship between cigarette smoking and PD. Environmental factors, especially exposures to paraquat and herbicides/pesticides, may play important roles in the development of PD in Taiwan.

This retrospective cohort study aimed to examine the relationship between herpes zoster ophthalmicus (HZO) and the subsequent risk of dementia using a population-based database. We retrieved the study sample from the Taiwan Longitudinal Health Insurance Database 2005. The study group included 846 patients with HZO, and the comparison group included 2538 patients without HZO. Each patient was individually followed for a 5-year period to identify those patients who subsequently received a diagnosis of dementia. We performed a Cox proportional hazards regression to calculate the hazard ratios (HRs) along with 95% confidence intervals (CIs) for dementia during the follow-up period between patients with HZO and comparison patients. The respective incidence rates of dementia per 1000 person-years were 10.15 (95% CI: 7.22~13.87) and 3.61 (95% CI: 2.61~4.89) for patients with HZO and comparison patients. The Cox proportional analysis showed that the crude HR of dementia during the 5-year follow-up period was 2.83 (95% CI: 1.83–4.37) for patients with HZO than comparison patients. After adjusting for patients’ characteristics and comorbidities, HZO patients were still at a 2.97-fold greater risk than comparison patients for developing dementia. Furthermore, we found that of sampled male patients, the crude HR of dementia for patients with HZO was as high as 3.35 (95% CI = 1.79–6.28) compared to comparison patients. This study demonstrated an association between HZO and dementia. Clinicians must be alert to suspect dementia in patients with cognitive impairment who had prior HZO.

We observed an increased risk for the subsequent development of a number of cancers among subjects with CP.

No abstract

The thyroid hormone 3,3 0 ,5-triiodo-L-thyronine (T 3 ) regulates growth, development, and differentiation processes in animals. These activities are mediated by the nuclear thyroid hormone receptors (TRs). Microarray analyses were performed previously to study the mechanism of regulation triggered by T 3 treatment in hepatoma cell lines. The results showed that spondin 2 was regulated positively by T 3 . However, the underlying mechanism and the physiological role of T 3 in the regulation of spondin 2 are not clear. To verify the microarray results, spondin 2 was further investigated using semi-quantitative reverse transcription-PCR and western blotting. After 48 h of T 3 treatment in the HepG2-TRa1#1 cell line, spondin 2 mRNA and protein levels increased by 3.9-to 5.7-fold. Similar results were observed in thyroidectomized rats. To localize the regulatory region in spondin 2, we performed serial deletions of the promoter and chromatin immunoprecipitation assays. The T 3 response element on the spondin 2 promoter was localized in the K1104/K1034 or K984/K925 regions. To explore the effect of spondin 2 on cellular function, spondin 2 knockdown cell lines were established from Huh7 cells. Knockdown cells had higher migration ability and invasiveness compared with control cells. Conversely, spondin 2 overexpression in J7 cells led to lower migration ability and invasiveness compared with control cells. Furthermore, this study demonstrated that spondin 2 overexpression in some types of hepatocellular carcinomas is TR dependent. Together, these experimental findings suggest that spondin 2, which is regulated by T 3 , has an important role in cell invasion, cell migration, and tumor progression.

Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showed that disruption of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy-related 7) via adeno-associated virus (AAV) vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase), which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from DENinduced hepatotoxicity or carcinogenesis.

This nationwide study aimed to provide risk estimates for a panel of infections subsequent to pyogenic liver abscesses (PLA) in Taiwan. In this study, we selected 12 050 patients diagnosed with PLA as our study cohort and 60 250 non-PLA patients as our comparison cohort. We individually tracked each subject for a 1-year period beginning with their index date to identify those who were subsequently diagnosed with any of the following infections: pneumonia, endophthalmitis, septic pulmonary embolism, pulmonary abscess, pleural empyema, meningitis, abscess of prostate, renal and perinephric abscess, epidural spinal abscess, osteomyelitis, necrotizing fasciitis, splenic abscess, psoas abscess and infectious endocarditis. We found that during the 1-year follow-up period, the subjects with PLA had a consistently higher incidence of all types of infections than comparison subjects. In particular, compared with subjects without PLA, the adjusted hazard ratios (HR) of pulmonary abscess, pleural empyema, renal and perinephric abscess, epidural spinal abscess and splenic abscess were 26.71, 18.56, 43.21, 51.32 and 126.51, respectively. We further analysed the HR of extra-hepatic Klebsiella pneumoniae infections among patients with PLA caused by K. pneumoniae. We found that the HR was higher for 12 of the 15 analysed extra-hepatic infections after restricting the analysis to only infections with K. pneumoniae aetiologies.

BackgroundPsoriasis is a prevalent autoimmune disorder. Various studies have reported on the relationship between psoriasis and chronic diseases but very few have explored the association between psoriasis and subsequent acute infection. This retrospective cohort study aimed to compare the risk of pneumonia between subjects with and those without psoriasis.MethodsThe medical records of 14,022 patients with psoriasis and 14,022 without psoriasis were obtained from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was followed-up for a three-year period. Cox proportional hazard regressions were performed to compare difference of subsequent pneumonia incidence between subjects with and those without psoriasis.ResultsThere were 206 (1.47%) subjects with psoriasis and 138 (0.98%) without psoriasis hospitalized for pneumonia. By Cox proportional hazard regressions analysis, the HR (hazard ratio) of pneumonia requiring hospitalization for patients with psoriasis was 1.50 (95% confidence interval [CI]: 1.21–1.86) compared to patients without psoriasis. The adjusted HR was 1.40 (95% CI: 1.12–1.73). The adjusted HR of pneumonia hospitalization for subjects with mild and severe psoriasis was 1.36 (95% CI: 1.09–1.70) and 1.68 (95% CI: 1.12–2.52), respectively, compared to those without psoriasis.ConclusionsPatients with psoriasis have significantly higher incidence of pneumonia compared to those without psoriasis.