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Objective We present a rare case of well-differentiated papillary mesothelioma (WDPM) found incidentally in a 59-year-old woman with endometrial cancer. Case report A 59-year-old nulliparous obese woman with a past history of hypertension and diabetes mellitus presented with postmenopausal bleeding for 11 months. Two months prior to this admission, an episode of massive vaginal bleeding lasting for a day was noticed by the patient. Hysteroscopy was performed after her visit to our outpatient department. Papillary tumors with active bleeding were found in the uterine cavity. Endometrial biopsy showed adenocarcinoma, endometrioid type characterized by papillary architecture lined by columnar cells with mild nuclear pleomorphism. The patient proceeded to magnetic resonance imaging (MRI), which demonstrated a 6.4 × 5.5 × 4.9 cm intrauterine mass. Her tumor marker levels were elevated (CA 125 87.8 IU/ml, CA19-9160.54 IU/ml). The patient then underwent a staging surgery and final pathology revealed stage IA endometrial cancer. During surgery, multiple nodules were found in the peritoneum, initially considered as tumor metastasis and eventually proved to be WDPM. Conclusion In conclusion, the simultaneous occurrence of WDPM with endometrial cancer is a rare entity. Although no standardized treatment has been established, WDPMs have a relatively favorable prognosis compared to malignant mesotheliomas.

Background The aim of this study is to present our experience of thoracic endovascular aortic repair (TEVAR) for type A intramural hematoma (TAIMH) and retrograde thrombosed type A aortic dissection (rt-TAAD) with the entry tear in the descending aorta or the abdominal aorta and discuss the outcomes. Methods We retrospectively reviewed total 6 patients who underwent TEVAR for TAIMH (n = 2) or rt-TAAD (n = 4) in our hospital between September 2017 and July 2019. The mean age of the patients (5 men and 1 woman) was 74 ± 13 years, and the mean follow-up duration was 13 ± 7 months. Results TEVAR was successfully performed in the acute phase in all patients without relevant complications. After TEVAR, the shrinkage of enlarged thoracic aorta and complete resorptions of the false lumen of the entire thoracic aorta were achieved in 4 patients. In the remaining 2 patients, one had residual thrombosed false lumen of the ascending aorta due to a new development of PAU at the distal aortic arch and another needed additional endovascular intervention for ascending aorta hematoma progression. Late aorta-related adverse event was observed in one patient, who needed open aortic repair. There was no death during follow-up. Conclusions Tear-oriented endovascular aortic repair is a potential option in selected patients of TAIMH and rt-TAAD and has shown favorable immediate outcomes and aortic remodeling. However, the late aorta-related adverse event is not negligible, and their long-term outcome has not been fully clarified. More research is warranted.

The receptor for advanced glycation end products (RAGE) overexpression was suggested to be associated with prostate cancer development and poor prognosis. In this study, we focused on the correlations between the clinicopathological characteristics and susceptibility of prostate cancer and RAGE single‐nucleotide polymorphisms (SNPs). In 579 prostate cancer patients, the RAGE SNPs rs1800625, rs1800624, rs2070600 and rs184003 in patients with or without grade group upgrade were analysed with real‐time polymerase chain reaction. The results demonstrated that the prostate cancer patients who carried the RAGE SNPs rs2070600 ‘GA’ genotypic variants were significantly associated with lower risk to develop grade group upgrade. Moreover, patients with the RAGE rs1800625 ‘TC + CC’ genotypic variants were associated with higher risk of perineural invasion. In 343 prostate cancer patients who carried the RAGE rs1800625 ‘TC + CC’ genotype without grade group upgrade were correlated with higher risk of biochemical recurrence and perineural invasion. In the analysis of TCGA database, significant differences of the RAGE mRNA level were found between the normal controls and prostate cancer patients (p

OBJECTIVESFew reports on the outcomes of patients treated for Stanford type A acute aortic intramural haematoma (TAAIMH) and retrograde thrombosed type A acute aortic dissection exist. This study aimed to evaluate their long-term results and predictors of adverse outcomes.METHODSWe retrospectively analysed 40 patients with TAAIMH and retrograde thrombosed type A acute aortic dissection. All patients underwent urgent surgery on presentation of life-threatening complications. Before discharge, 18 patients underwent open aortic surgery, and 22 were treated with medical therapy alone. Clinical features of these patients and image appearances were reviewed, and the relationship with overall survival, aortic events, and aortic death was investigated.RESULTSThe in-hospital mortality rate was 4.5% (1 patient) with medical therapy alone and 11.1% (2 patients) with surgical intervention. No patient with initial medical therapy required urgent surgery for life-threatening complications beyond 3 days of admission. The overall survival and aortic death-free survival rates at 1, 5 and 10 years were 85.0%, 72.5% and 59.8% and 90.0%, 81.6% and 77.1%, respectively. TAAIMH associated with penetrating aortic ulcer (PAU) was a risk factor of aortic events (P = 0.020) and significantly influenced aortic death-free survival (P = 0.003).CONCLUSIONSUrgent surgery for complicated TAAIMH and retrograde thrombosed type A acute aortic dissection patients and initial medical therapy for uncomplicated patients show favourable long-term survival rates. TAAIMH is frequently associated with PAU; PAU enlargement is common. Although PAU can remain stable for years, it is a strong predictor of poor prognosis. For optimal long-term results, surgical repair is recommended for TAAIMH associated with PAU.

Glycated hemoglobin (HbA1c) has been recommended as a standard indicator of long-term glycemic control for diabetic and non-diabetic patients, within the in vitro diagnostic (IVD) industry that is focused on the development of point-of-care (POC) methods with improved operational convenience and shorter measurement time. In this study, we evaluated the measurement accuracy performance of a recently commercialized POC HbA1c analyzer, PixoTest POCT System (iXensor Co., Ltd.) that is portable, intuitive and wireless data transmission enabled. For PixoTest POCT accuracy evaluation, TOSOH G7 Analyzer (TOSOH Bioscience GmbH) was used as a reference method and performed in accordance with CLSI EP 09-A3 guidelines. This study enrolled one hundred and twenty (120) subjects from three clinical sites (40 subjects each), administered through nine (9) trained operators (total) performed under manufacturer’s protocol using three reagent lots per blood sample (capillary & venous). Linear regression, bias plot and other statistical analyses were extrapolated from the test data. Passing-Bablok regression analysis of the data between PixoTest POCT System and TOSOH G7 Analyzer with the venous blood showed a slope of 1.03 and an intercept of − 0.1 and a correlation coefficient of 0.99. The results for capillary blood showed a slope of 1.01 and an intercept of − 0.04 and a correlation coefficient of 0.99. The PixoTest POCT System’s performance is similar to TOSOH G7 Analyzer in accuracy and linearity. Therefore, the system’s HbA1c test capability is ideal for the management of chronic disease, as a user convenient and efficient POC solution.

Aim To investigate the association between specific dental therapy for periodontal disease and the risk of ischaemic stroke. Materials and methods We conducted a population-based cohort study that used data from the Taiwan National Health Insurance Research Database 2005 for the period of 2000-2013. Our observations focused on patients with the diagnoses of gingivitis or periodontitis with and without specific treatment and subsequent incidence of ischaemic stroke. Dental care services include dental scaling, intensive treatment (subgingival curettage and root planing) and tooth extraction. Multivariate Cox regression analysis was used to estimate the hazard ratios and corresponding 95% confidence intervals (95% CI). Results Compared with those in the gingivitis cohort, patients with periodontitis have a higher risk of ischaemic stroke and a lower survival rate of stroke over the 10-year follow-up period. After integrative dental care, both dental scaling and intensive treatment, the risk was reduced, especially in patients with periodontitis, while patients with periodontal disease may have an increased risk of stroke after tooth extraction therapy. Conclusions Our study showed that periodontitis is a risk factor for ischaemic stroke. Both dental scaling and intensive treatment for periodontal disease are associated with a lower risk of further ischaemic stroke events.

Background Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being utilized in patients with massive pulmonary embolism (PE). However, the efficacy and the safety remain uncertain. This study aimed to investigate clinical courses and outcomes in ECMO-treated patients with acute PE. Methods Twenty-one patients with acute PE rescued by ECMO from January 2012 to December 2019 were retrospectively analysed. Clinical features, laboratory biomarkers, and imaging findings of these patients were reviewed, and the relationship with immediate outcome and clinical course was investigated. Results Sixteen patients (76.2%) experienced refractory circulatory collapse requiring cardiopulmonary resuscitation (CPR) or ECMO support within 2 h after the onset of cardiogenic shock, and none could receive definitive reperfusion therapy before ECMO initiation. Before or during ECMO support, more than 90% of patients had imaging signs of right ventricular (RV) dysfunction. In normotension patients, the computed tomography (CT) value was a valuable predictor of rapid disease progression compared with cardiac troponin I level. Ultimately, in-hospital death occurred in ten patients (47.6%) and 90% of them died of prolonged CPR-related brain death. Cardiac arrest was a significant predictor of poor prognosis (p = 0.001). Conclusions ECMO appears to be a safe and effective circulatory support in patients with massive PE. Close monitoring in intensive care unit is recommended in patients with RV dysfunction and aggressive use of ECMO may reduce the risk of sudden cardiac arrest and improve clinical outcome.

Background Ascending aortic thrombus (AAT) in a nonaneurysmal aorta is an extremely rare event and has potentially catastrophic complications, with a life-threatening risk of myocardial infarction and cerebral embolization. This systematic review aims to elucidate the clinical manifestations and to compare the outcomes of anticoagulation therapy versus open aortic surgery for AAT. Methods The MEDLINE/PubMed databases were extensively searched between 1995 and 2019. All relevant publications on AAT in adults were reviewed, and individual patient data were pooled in this meta-analysis. The primary outcome was AAT resolution. The adverse outcome variables were recurrent arterial embolic events, complications related to open aortic surgery, and mortality during the study period. Chi-squared test and logistic regression analysis were used to compare groups and identify any predictors of mortality. Results Overall, 107 patients from 101 articles were included, of whom 29 patients who received anticoagulation therapy and 59 who underwent open aortic surgery were included in the outcome analysis. Among 29 patients treated with initial anticoagulation therapy, the persistence of AAT was observed in 11 patients (38%) and recurrent arterial embolization was developed in 6 patients (21%). All 11 patients in the anticoagulation group underwent secondary aortic surgery for the persistence of AAT with uneventful postoperative course. Compared with patients treated with primary aortic surgery, patients treated with initial anticoagulation therapy had higher risk of recurrent embolization (P = 0.002). No significant difference existed in the mortality rates between the groups (P = 0.106). Hemodynamic instability was an independent predictor of mortality (P = 0.008). Conclusions Anticoagulation therapy and open aortic surgery for AAT show similar results; however, open aortic surgery reliably removes AAT and reduces the risk of recurrent embolization compared with anticoagulation therapy. Furthermore, the preoperative hemodynamic status significantly influences the clinical outcome and is a strong predictor of prognosis.

Blood glucose measurements help to guide insulin therapy, thus reducing disease severities, secondary complications, and related mortalities. Efforts are underway to allow diabetes patients to experience a more convenient way to measure blood glucose and consequently increase their adherence to regular self-monitoring of blood glucose (SMBG). This study demonstrated a new SMBG system that integrated all components of a glucometer via a smartphone’s optical sensing module to detect the colorimetric blood strip and obtains the blood glucose concentration with calculations performed by an application install in the smartphone. To validate the accuracy and applicability of the new SMBG system regarding the ISO15197:2013 accuracy criteria and patient requirements, a clinical trial and usability survey involving participants from different age groups were conducted in collaboration with the China Medical University, where enrolled 120 diabetic patients were asked to operate the new SMBG system to measure their blood glucose concentration, and feedback was obtained from their user experience. The results showed that three different reagent system lots fulfilled the accuracy requirements with values of 97.4–97.5% , and all of the data were within zones A and B of the consensus error grid, which satisfies the ISO 15197:2013 requirement. The usability survey showed that 97.5% of the participants found the operations convenient, and 100% found the design easy for carrying. This new system could lead to improvements in blood glucose monitoring by people with diabetes, and thus, better management of the disease.

Glioblastoma (GBM) is the most mortality brain cancer in the world. Due to high invasion and drug resistance cause the poor prognosis of GBM. Naringenin, an ingredient of citrus, exhibits many cellular functions such as antioxidant, anti-inflammation, and anticancer. Naringenin inhibits the migration of bladder and lung cancer via modulation of MMP-2 and/or MMP-9 activities, Naringenin inhibits migration and trigger apoptosis in gastric cancer cells through downregulation of AKT pathway. However, the effects of naringenin in GBM still remain to be elucidated. In this study, we reveal the molecular mechanisms of naringenin in the inhibition of migration and invasion in GBM. No overt alternation of cell proliferation was found in of GBM 8901 cells treated with different concentration of naringenin. Slight decreased cell viability was found in GBM 8401 cell treated with 200 and 300 μM naringenin. Significant reduction of migration and invasion as assayed by Boyden chamber analysis was found in of GBM cells treated with 100, 200, and 300 μM naringenin. Zymography analysis also revealed that the activities of MMP-2 and MMP-9 of GBM cells were significantly inhibited in response to 100, 200, or 300 μM naringenin treatment. Proteins of MMP-2 and MMP-9 were downregulated in naringenin treated GBM cells. In addition, naringenin also attenuated the activities of ERK and p38. Naringenin decreased mesenchymal markers (snail and slug) expression as revealed by Western blot analysis. Taken together, our findings indicated that naringenin eliminated the migration and invasion of GBM cells through multiple mechanisms including inhibition of MMPs, ERK, and p38 activities and modulation of EMT markers. Our results also suggested that naringenin may be a potential agent to prevent metastasis of GBM.

Parkinson's disease (PD) is a progressive motor neurodegenerative disorder, characterized by a selective loss of dopaminergic neurons in the substantia nigra. The complexity of disease etiology includes both genetic and environmental factors. No effective drug that can modify disease progression and protect dopamine neurons from degeneration is presently available. Human α-Synuclein A30P (A30P) is a mutant gene identified in early onset PD and showed to result selective dopamine neuron loss in transgenic A30P flies and mice. Paraquat (PQ) is an herbicide and an oxidative stress generator, linked to sporadic PD. We hypothesized that vital PD modifier genes are conserved across species and would show unique transcriptional changes to oxidative stress in animals expressing a PD-associated gene, such as A30P. We also hypothesized that manipulation of PD modifier genes would provide neuroprotection across species. To identify disease modifier genes, we performed two independently-duplicated experiments of microarray, capturing genome-wide transcriptional changes in A30P flies, chronically fed with PQ-contaminated food. We hypothesized that the best time point of identifying a disease modifier gene is at time when flies showed maximal combined toxicity of A30P transgene and PQ treatment during an early stage of disease and that effective disease modifiers gene are those showing transcriptional changes to oxidative stress in A30P expressing and not in wild type animals. Fly Neprilysin3 (Nep3) is one identified gene that is highly conserved. Its mouse and human homolog is endothelin-converting enzyme-1 (Ece1). To investigate the neuroprotective effect of Ece1, we used NS1 cells and mouse midbrain neurons expressing A30P, treated with or without PQ. We found that ECE1 expression protected against A30P toxicity on cell viability, on neurite outgrowth and ameliorated A30P accumulation in vitro. Expression of ECE1 in vivo suppressed dopamine neuron loss and alleviated the corresponding motor deficits in mice with A30P-expression. Our study leverages a new approach to identify disease modifier genes using a stress-enhanced PD animal model.

Previous studies demonstrated that both diabetes and flunarizine use can increase the risk of parkinsonism. The aim of the current study was to investigate the risk of developing parkinsonism after flunarizine treatment, in a cohort of patients newly diagnosed with type 2 diabetes. We conducted a nested case-control study of a type 2 diabetic cohort from the Taiwan Longitudinal Health Insurance Database 2005 (LHID 2005). Each incident case of parkinsonism, during the period from 2001 to 2013, was randomly matched with 3-10 controls, according to age, sex, calendar year of cohort entry, and the duration of follow-up. Conditional logistic regression was used to estimate the odds ratio (OR) of parkinsonism associated with flunarizine use. The cohort consisted of 44,644 patients with newly diagnosed type 2 diabetes from 2001 to 2013, of whom 464 patients had a parkinsonism event during the follow-up period. The adjusted OR of parkinsonism with relation to flunarizine use was 2.75 (95% confidence interval: 2.26-3.36). There were also duration- and dose-response effects. Compared to those who had not used it, the OR for developing parkinsonism was 1.77 for patients who used flunarizine for less than 1 month. When the exposure period expanded over 3 months, the OR increased to 7.03. Our findings suggested that flunarizine use is a potential risk factor for parkinsonism in patients with newly diagnosed type 2 diabetes, especially when the drug is persistently used for over 3 months.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Introduction Right heart free-floating thrombus in the absence of structural heart disease or atrial fibrillation is rare. When it travels to the heart into the lung, called thrombus-in-transit, may cause cardiopulmonary collapse and sudden death. The clinical presentation varies from mild respiratory symptoms to sudden death; however, there are few clinical case reports of giant, free-floating thrombus in the right heart in an asymptomatic patient, and the optimal management options have not been established. Patient concerns A 36-year-old Asian woman presented to the emergency department with complaints of worsening swelling of the left lower extremity over 12 hours. Diagnosis Left leg deep vein thrombosis accompanied by an asymptomatic giant right atrial thrombus and pulmonary embolism with a rare autoimmune disease of Evans syndrome. Interventions Emergent surgical thrombectomy under cardiopulmonary bypass for right atrial thrombus. Outcomes The postoperative course was uneventful, and she was discharged on the eighth postoperative day with normal heart function and mild tricuspid regurgitation. Conclusion An additional diagnostic workup in cases of deep vein thrombosis is necessary for the rapid diagnosis of right heart thrombus and pulmonary embolism without delay. This case report illustrates that early recognition of venous thromboembolism and emergent thrombectomy of right heart thrombus-in-transit is crucial to prevent mortality.

Objective The aim of this study was to investigate the pattern of ergotamine prescription and overuse in Taiwan. Background Ergotamine is a frequently prescribed medication for the treatment of migraine, although excessive use may lead to medication-overuse headache. Methods We conducted a retrospective cohort study by using the Longitudinal Health Insurance Database 2005 in Taiwan. Patients enrolled in the study were between the ages of 18 and 80 years, received at least two prescriptions of ergotamine, and follow-up for more than 1 year at outpatient clinics during 1999 to 2013. Each ergotamine prescription was converted into a defined daily dose (DDD) and patients were sorted into two groups: occasional users, having fewer than 3 consecutive months of use, and regular users, with 3 consecutive months of use or more. Regular users were further divided into overusers (DDDs ≥ 10 per month) and non-overusers. Results A total of 41,023 migraine patients were enrolled in the study; 5803 patients were classified as regular users, with 859 of those being overusers. Of the ergotamine overusers, around 698/859 (82%) continued to use, and 443/859 (52%) remained overusers of ergotamine in the subsequent year after the index date. The most frequently prescribed prophylactic medications were propranolol and flunarizine, which were prescribed in 30.4% and 20.0% of overuse patients, respectively. Conclusions Ergotamine overuse remains common in Taiwan, while prophylactic medicine is still underutilized. More education on ergotamine-overuse headache is needed to improve awareness.

Background/Aim: Metalloproteinases (MMPs) are a family of multifunctional proteins reported to be overexpressed in several types of cancers. However, the contribution of MMP8 genotype to oral cancer has not been elucidated. In this study, we focused on the contribution of polymorphisms in the promoter region of MMP-8 (C-799T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to Taiwanese oral cancer. Materials and Methods: In this case-control study, MMP-8 genotype, was examined among 788 patients with oral cancer and 956 gender- and age-matched healthy controls regarding its potential to determine oral cancer risk. Results: The distributions of MMP-8 C-799T, Val436Ala and Lys460Thr genotypes were not different between the oral cancer and non-cancer control groups. We also analyzed the allelic frequency distributions and no significant difference was found. As for gene-environment interaction analysis, there was an increased risk for smokers, alcohol drinkers or betel quid chewers with variant MMP-8 C-799T or Val436Ala genotypes. Conclusion: Our findings suggest that the polymorphisms at MMP-8 C-799T or Val436Ala may not play a major role in mediating personal risk of oral cancer; however, the detailed mechanisms require further investigation.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Background: Metoclopramide is used to relieve gastrointestinal symptoms, however, it could cause adverse reactions of motor disorders. The aim of this study was to investigate whether metoclopramide treatment has a duration–response or dose–response effect and to estimate the risk of developing Parkinsonism following different and specific durations of treatment. Methods: A cohort study of newly diagnosed type 2 diabetes mellitus in 45- to 79-year-old patients, between 1999 and 2008, was selected using the Longitudinal Health Insurance Database 2005. A nested case–control study was conducted in the diabetes cohort in which all incident cases of Parkinsonism were identified. We randomly matched each case with up to 10 controls from the risk set. Conditional logistic regression was utilized to estimate odds ratio of Parkinsonism associated with metoclopramide use. Results: A total of 34,685 patients with diabetes were assembled as the cohort, and 541 incident Parkinsonism cases were identified. There were duration–response and dose–response effects on the risk of developing Parkinsonism. Compared with never-use patients, the adjusted odds ratios (ORs) of continuing therapy for 0–1 month, 1–2 months, 2–3 months, 3–5 months, and more than 5 months were 1.17 [95% confidence interval (CI) 0.93–1.45], 1.44 (95% CI 1.04–2.00), 1.74 (95% CI 1.14–2.65), 1.90 (95% CI 1.23–2.93), and 2.17 (95% CI 1.50–3.12), respectively. Conclusions: With metoclopramide treatment, regardless of less or more than 3 months of use, the risk of developing Parkinsonism in patients with newly diagnosed diabetes escalated with the duration of therapy. Therefore, we recommend close monitoring for the development of Parkinsonism in patients treated with metoclopramide, particularly (but not limited to) those with prolonged exposure.

Prostate cancer is one of the major cancers of the genitourinary tract. High-mobility group box 1 (HMGB1) was suggested as a promising therapeutic target for prostate cancer. In this study, we aim to elucidate the associations of HMGB1 single nucleotide polymorphisms (SNPs) with prostate cancer susceptibility and clinicopathological characteristics. The HMGB1 SNPs rs1412125, rs2249825, rs1045411, and rs1360485 in 579 prostate cancer patients and 579 cancer-free controls were analyzed with real-time polymerase chain reactions (real-time PCR). All of the data were evaluated with SAS statistical software. Our results showed that the HMGB1 rs1045411 T allele genotype was significantly associated with advanced pathologic T stage (odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.021‒2.012, p = 0.037) and pathologic N1 stage (OR = 2.091, 95% CI = 1.160‒3.767, p = 0.012), and the rs1360485 polymorphic CT + TT genotype was associated with pathologic Gleason grade group (4 + 5) (OR = 1.583, 95% CI = 1.017‒2.462, p = 0.041), pathologic T stage (3 + 4) (OR = 1.482, 95% CI = 1.061‒2.070, p = 0.021), and pathologic N1 stage (OR = 2.131, 95% CI = 1.178‒3.852, p = 0.011) compared with their wild-type carriers. In conclusion, our results revealed that the HMGB1 SNPs were associated with the clinical status of prostate cancer. The HMGB1 SNPs may have the potential to predict prostate cancer disease progression.

Maintaining appropriate insulin levels is very important for diabetes patients. Effective monitoring of blood glucose can aid in maintaining the body’s insulin level, and thus reduce disease severities, secondary complications, and related mortalities. However, existing blood glucose measurement devices are inconvenient to carry and involve complex procedures, reducing the willingness of diabetes patients to regularly measure blood glucose. We aim to provide a rapid, convenient, and portable meter for diabetes patients. We introduce an integrated blood glucose detection device (IBGDD) that has no electronic component and uses the optical sensing module of a smartphone to inspect colorimetric blood strips. To demonstrate accuracy conformance of the developed device to the ISO 15197:2013 standard for blood glucose measurement, 20 diabetes mellitus patients used the IBGDD with smartphones to measure their blood glucose level. The measurement results revealed an accuracy of 100%, completely satisfying the requirements of the ISO 15197:2013 standard. Overall, our specially designed IBGDD with a smartphone could achieve high accuracy and convenient usage for the measurement of blood glucose concentration. Furthermore, the device is highly portable and simple to operate. This contributes toward achieving self-monitoring of blood glucose by diabetes patients and improved mobile health in the future.

The clinical features of parkinsonism in carbon monoxide (CO) intoxication have been associated with striatal-related neuronal networks. As parkinsonian and neuropsychiatric features are both related to presynaptic dopaminergic integrity, the aim of this study was to explore the clinical significance of 99mTcTRODAT-1 in grading neurobehavioral scores and parkinsonian severity in CO intoxication. We enrolled 64 patients with CO intoxication, including 29 with parkinsonism (parkinsonism[+] group) and 35 without (parkinsonism[-] group). All of the patients received 99mTcTRODAT-1 neuroimaging evaluations, comprehensive neurobehavioral tests and assessments of the severity of parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS)-part III motor score. Univariate and multivariate regression analyses were used to test the predictive factors and scores for a diagnosis of parkinsonism and its severity. The parkinsonism(+) group had significantly lower cognitive scores and higher neuropsychiatric total scores compared with the parkinsonism(-) group, both of which were independently related to the severity of parkinsonism. 99mTcTRODAT-1 regional caudate signals were correlated with tremors at rest, action or postural tremors of the hands, bradykinesia and hypokinesia, and visuospatial, verbal fluency, abstract thinking and digit backwards scores. Scores of the neurobehavioral tests and UPDRS items were highly correlated (p

Bidirectional co-morbidity between migraine and depression has been observed. Mood disorders are associated with an increased risk of both migraine and irritable bowel syndrome (IBS). The aim of this study was to evaluate the risk of developing IBS in patients with migraine and to compare the risks between those with and without anxiety or depression. This research used the data contained in the National Health Insurance Research Database (NHIRD). A total of 2859 subjects with migraine and 5718 age-, sex-, hypertension-, diabetes-, mood disorder-matched controls were identified. Both cohorts excluded subjects with pre-existing catastrophic illness and IBS diagnosed before the index visit or within 30days after the index visit. All individuals of both cohorts were tracked until either having the diagnosis of IBS, loss of follow-up, or IBS free up to 7years. During the 7-year follow-up period, 8.4% of patients with migraine and 5.4% of control cohort developed IBS. Migraine is associated with an increased risk of developing IBS (HR=1.58, 95% CI: 1.33-1.87). When separating the cohort into those with mood disorder and without it, migraine is a significant risk factor of IBS in patients without mood disorders, but not in patients with co-existed mood disorders. The findings of this study suggest that migraine is a risk factor of future IBS development for those without comorbid anxiety or depression. However, migraine does not contribute significantly additional risk to IBS development in patients with comorbid anxiety or depression.

Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized by bradykinesia, rigidity and tremor, constituting difficulties in walking and abnormal gait. Previous research shows that Drosophila expressing human α-synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis climbing is a different movement modality from walking. Whether A30P flies would exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is not known. In this study, we characterized A30P fly walking using a high-speed camera and an automatic behavior tracking system. We found that old but not young A30P flies exhibited walking abnormalities, specifically decreased total moving distance, distance per movement, velocity, angular velocity and others, compared with old control flies. Those features match the definition of bradykinesia. Multivariate analysis further suggested a synergistic effect of aging and A30P, resulting in a distinct pattern of walking deficits, as seen in aged A30P flies. Psychiatric problems are common in PD patients with anxiety affecting 40–69% of patients. Central avoidance is one assessment of anxiety in various animal models. We found old but not young A30P flies exhibited increased centrophobism, suggesting possible elevated anxiety. Here, we report the first quantitative measures of walking qualities in a PD fly model and propose an alternative behavior paradigm for evaluating motor functions apart from climbing assay.

Background: The direct impact of medical expenses on breast cancer incidence and mortality rate has not been sufficiently addressed. The purpose of this study is to investigate the potential correlation between the incidence and mortality rate of breast cancer and the medical expenses in Taiwan. Materials and Methods: Breast cancer cases were identified from the National Health Insurance Research Database (NHIRD) with corresponding to International Classification of Diseases, and the Ninth Revision (ICD-9) code 174, 1740-1749, 175, 1750 and 1759 from January 1999 to December 2006. Age-specific incidences were estimated by population data obtained from the Department of Statistics, Ministry of the Interior. Medical expenses, including outpatient and inpatient services, were also retrieved from the NHIRD. Results: The incidence increased from 20.06 per 100,000 in 1999 to 30.34 per 100,000 in 2006; the total expenses increased from 1,449,333,521 in 1999 to 4,350,400,592 Taiwan dollars in 2006. The age-standardized mortality rate for female breast cancer remained essentially unchanged, while the age-standardized incidence increased steadily (except 2002-2003). Among the top 20 coexisting ICD-9 codes for expenses, four are directly on cancers, while 16 are on other diseases or symptoms, which are not necessarily caused by breast cancer. Conclusions: Significantly increased medical expenditure on breast cancer failed to bring down its mortality and incidence rate. The finding has implications for healthcare policy planners in proposing strategies for breast cancer control and allocating the resources.

Biomaterials are often added to autologous fat grafts both as supporting matrices for the grafted adipocytes and as cell carrier for adipose-derived stem cells (ADSCs). This in vivo study used an autologous fat graft model to test a lamininalginate biomaterial, adipocytes, and ADSCs in immune-competent rats. We transplanted different combinations of shredded autologous adipose tissue [designated “A” for adipose tissue]), laminin-alginate beads [designated “B” for bead], and ADSCs [designated “C” for cell]) into the backs of 15 Sprague-Dawley rats. Group A received only adipocytes, Group B received only laminin-alginate beads, Group AB received adipocytes mixed with laminin-alginate beads, Group BC received laminin-alginate beads encapsulating ADSCs, and Group ABC received adipocytes and laminin-alginate beads containing ADSCs. Seven-tesla magnetic resonance imaging was used to evaluate the rats at the 1st, 6th, and 12th weeks after transplantation. At the 12th week, the rats were sacrificed and the implanted materials were retrieved for gross examination and histological evaluation. The results based on MRI, gross evaluation, and histological data all showed that implants in Group ABC had better resorption of the biomaterial, improved survival of the grafted adipocytes, and adipogenic differentiation of ADSCs. Volume retention of grafts in Group ABC (89%) was also significantly greater than those in Group A (58%) (p

Online fitness videos make it possible and popular to do exercise at home. However, it is not easy to notice the details of motions by merely watching training videos. We propose a new type of motion guidance system that simulates the way that the human body moves as driven by muscle contractions. We have designed external artificial muscles on a sleeve to create a pulling sensation that can guide the forearm's pronation (internal rotation) and the forearm's supination (external rotation). The sleeve consists of stepper motors to provide pulling force, fishing lines and elastic bands to imitate muscle contraction to drive the forearm to rotate instinctively. We present two preliminary experiments. The first one shows that this system can effectively guide the forearm to rotate in the correct direction. The second one shows that users can be guided to the targeted angle by utilizing a tactile cue. We also report users' feedback through the experiments and provide design recommendations and directions for future research.

Summary Purpose The impact of epilepsy following different subtypes of stroke is unclear. The aim of this study was to evaluate the risk of post-stroke epilepsy with different stroke subtypes. Methods A total of 4126 stroke patients and 24,756 age- and sex-matched controls were retrieved from the Longitudinal Health Insurance Database 2005, a major dataset of the National Health Insurance Research Database, from 2000 to 2003. All were then individually tracked to their last medical visit up to five years from 30 days after their first-ever stroke incident to identify those who developed epilepsy. Results Among the 4126 stroke patients, 72.2% had ischemic stroke, 14.7% had intracerebral hemorrhage (ICH), 2.3% had subarachnoid hemorrhage (SAH), 2.0% had other and unspecified intracranial hemorrhage (OIH), including subdural hemorrhage and epidural hemorrhage, and 8.9% had multiple stroke subtypes. The adjusted hazard ratio for the development of epilepsy was 11.5 (95% CI 8.2–16.2) for the patients with stroke compared to the controls. 2.6% of the patients with stroke developed epilepsy during the 5-year follow-up period. The rate of post-stroke epilepsy was highest in patients with multiple subtypes (7.7%), followed by ICH (4.3%), SAH (4.2%), OIH (2.5%) and ischemic stroke (1.6%). Conclusion Stroke patients had a significantly higher risk of developing epilepsy than the controls. The risk of post-stroke epilepsy was higher in patients with hemorrhagic stroke than ischemic stroke.

Background Diabetes is associated with an increased risk of developing dementia. However, data on the patients with newly diagnosed type 2 diabetes are limited. Objective To investigate the relationship between newly diagnosed type 2 diabetes and the risk of developing dementia, ischemic stroke and intracranial hemorrhage after disease diagnosis and the interrelationship between dementia and the stroke events. Method Data were collected from the National Health Insurance Research Database of Taiwan. The study cohort included 3717 patients newly diagnosed with type 2 diabetes and 37,170 age- and sex-matched comparison patients from the same period. All patients were tracked for 7 years following their index visit in 2000–2001. Result After adjusting for potential confounders, dementia risk was approximately 63% higher (hazard ratio [HR], 1.63; 95% CI, 1.33–1.99) among newly diagnosed type 2 diabetic patients than among comparison subjects. Newly diagnosed type 2 diabetes also increased the risk of developing ischemic stroke but not intracranial hemorrhage. About 43.6% of diabetic patients who developed dementia also had ischemic stroke during the follow-up period, higher than the rate 29.6% in the comparison group. Conclusion This study shows that newly diagnosed type 2 diabetes is associated with a 63% higher future risk of dementia during the 7-year follow-up period. The high dementia and ischemic stroke overlap rate in the diabetic study group suggests vascular events play an important role in the pathogenesis of developing dementia.

The reported complication rates of the distal radius fractures vary widely from 6% to 80%. Unlike damage to neural and tendinous structures, vascular complications have been extremely rare. We described an unusual case of distal radius fracture complicated with digital gangrenes because of occlusion of radial and ulnar arteries.

Background: Little is known about the epidemiology of cryptococcal meningitis in Taiwan. The aim of this study was to conduct the first nationwide population-based epidemiologic study of cryptococcal meningitis in Taiwan. Methods: Cases of cryptococcal meningitis were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database with the corresponding ICD-9 code 321.0 from January 2000 to December 2007. Results: A total of 845 incident cases of cryptococcal meningitis were detected. Among them, 109 patients (12.9%) had human immunodeficiency virus (HIV) infection. The average incidence was 4.7 per million person-years. The incidence remarkably increased in the age group of 60–69 years, peaked in the age group of 70–79 years, and fell after the age of 80 years. The average incidence for men was 2.2-fold higher than that for women. The most common complication was obstructive hydrocephalus in 15.3% of the patients, followed by acute respiratory failure in 12.0% of the patients. Conclusion: This is the first population-based epidemiologic study of cryptococcal meningitis in Taiwan. The incidence was stable during the study period, and most cases were non-HIV related.

The definition and clinical significance of vertebral artery hypoplasia (VAH) remain inconclusive. VAH has been proposed as a predisposing factor of posterior circulation ischemic stroke. The aim of this study was to determine a best cut-off diameter of vertebral artery (VA) for VAH and to investigate if unilateral VAH is associated with a decrease in net vertebral flow volume. Retrospective data of 1000 presumably healthy subjects free of cerebrovascular disease or apparent carotid atherosclerosis were analysed. We found that a VA diameter

A number of hypotheses have been postulated to explain the development of syringomyelia associated with Chiari I malformation. However, the mechanism of syrinx development is still poorly understood. Furthermore, the outcomes of current surgical procedures have been variable. There is evidence that the syringomyelia can spontaneously resolve, and this may warrant a more conservative approach to monitor the progression of neurological deficits. In this paper, we present a patient with spontaneous regression of syringomyelia. The current aetiological theories are discussed.

Traumatic intracranial aneurysms are uncommon and represent fewer than 1% of all cerebral aneurysms. They may develop after blunt or penetrating head injuries and can present both diagnostic challenges and surgical difficulties. Because traumatic aneurysms are fragile and prone to rupture, early diagnosis with cerebral angiography and prompt treatment are essential. We present two patients with traumatic aneurysms and discuss their aetiology, classification, clinical presentations, diagnosis, and treatment options.

Objective Transient monocular blindness (TMB) attacks may occur during straining activities that impede cerebral venous return. Disturbance of cerebral and orbital venous circulation may be involved in TMB. Methods Duplex ultrasonography and Doppler-flow measurement of jugular and retrobulbar veins were performed in 134 consecutive patients with TMB and 134 age- and sex-matched control subjects. All recruited patients received thorough examinations to screen for possible underlying causes. Results Of the 134 patients with TMB, 48 patients had ipsilateral carotid arterial lesion and 7 patients had TMB attack(s) caused by cardiac embolism. Of the remaining 79 patients with undetermined cause, 46 had 3 or more TMB attacks (undetermined-frequent group) and 33 had fewer than 3 attacks. In comparison with the control subjects, the TMB patients had greater frequencies of jugular venous reflux (57 vs 30%; p < 0.0001; odds ratio [OR]: 3.079, 95% confidence intervals [CI]: 1.861–5.096) and flow reversal in the superior ophthalmic vein (RSOV; 37 vs 9%; p < 0.0001; OR: 6.052, CI: 3.040–12.048). The undetermined-frequent group had the greatest frequencies of jugular venous reflux (74%, 34 patients; OR: 6.66, CI: 3.13–14.17) and RSOV (59%, 27 patients; OR: 6.51, CI: 3.12–13.58). Of the 50 patients with RSOV, 47 (94%) had RSOV on the side of the TMB attacks. Interpretation The increased incidences of jugular and orbital venous reflux in TMB patients suggest that disturbance of cerebral and orbital venous circulation is involved in the pathogenesis of TMB, especially among patients with frequent attacks of undetermined cause. Ann Neurol 2008

Background Radiofrequency catheter ablation for paroxysmal atrial fibrillation is well established but not drawback free. Pulmonary vein stenosis is one of the complications and usually treated with stenting with the disadvantages of high re-stenosis rate and anticoagulant dependence. Case presentation Herein, we present the case of a 47 year-old lady, who suffered from fever and hemoptysis due to right inferior pulmonary vein occlusion after radiofrequency catheter ablation for paroxysmal atrial fibrillation. Eventually, thoracoscopic right lower lung lobectomy was inevitable with satisfactory result. Conclusions Pulmonary vein stenosis is a major complication after radiofrequency ablation of atrial fibrillation. High suspicion and early detection in patients with pulmonary manifestations are mandatory for salvage the injured lung in early. If delayed, surgical resection of the involved lung, especially through the thoracoscopic approach will eradicate the problem with minimal complication.

Background:Kennedy's disease (KD) is an X-linked recessive polyglutamine disease. Traditionally, it is a lower motor neuron syndrome with additional features such as gynecomastia and tremor. Sensory symptoms are minimal if ever present. We used multimodal evoked potential (EPs) tests to study the distribution of the involvement of the disease.Methods:Visual, brainstem auditory, somatosensory and motor EPs were studied in six KD patients. All of them had typical presentations and had been proved genetically.Results:Abnormal findings were noted as follows: prolonged peak latencies of visual EPs, increased hearing threshold level, inconsistent brainstem auditory EPs, decreased amplitudes of cortical potentials of somatosensory EPs, and increased motor threshold to transcranial magnetic stimulation.Conclusions:Our multimodal EP studies showed that KD involved multiple levels of the nervous system. It implies the widespread effects of the mutant androgen receptors.

Baroreflex sensitivity (BRS) and heart rate variability (HRV) are potential therapeutic targets. The present study was conducted to assess changes in BRS and HRV after monotherapy with losartan versus that of atenolol in uncomplicated essential hypertension. Thirty subjects with uncomplicated essential hypertension were randomized to receive atenolol 50 mg to 100 mg (n = 15) or losartan 50 mg to 100 mg (N = 15) daily for 6 months. Instantaneous systolic blood pressure (SBP) and heart rate were assessed using servo-controlled infrared finger plethysmography before treatment and at the end of 3 months and 6 months after treatment. The fluctuation in SBP and interpulse interval (IPI) was divided into three specific frequency ranges by fast Fourier transform as high frequency (HF; 0.15 Hz-0.4 Hz), low frequency (LF; 0.04 Hz-0.15 Hz), and very low frequency (VLF; 0.004 Hz-0.04 Hz). The BRS was expressed as (1) SBP-IPI transfer function with its magnitude in the HF and LF ranges and (2) BRS index alpha. The HRV was expressed as total power and power in the LF and HF ranges of interpulse interval. Blood pressure was reduced to a similar extent in both groups. Compared with the baseline, BRS did not improve in both groups at month 3. However, BRS was significantly improved in the losartan group (P0.05) but not in the atenolol group at month 6. In addition, BRS was significantly higher in the losartan group than the atenolol group at month 3 and month 6 (P0.05). Moreover, heart rate variability was significantly reduced in the atenolol group at month 6 (P0.05), but not in the losartan group. The HRV in the losartan group was significantly higher than that in the atenolol group at month 6 (P0.05). These findings suggest superior effects of losartan on BRS and HRV than atenolol in uncomplicated essential hypertension, which may be beyond blood pressure reduction/resetting.

Background Recurrent cellulitis is a vexing clinical problem with huge financial burden on healthcare resources. Though intramuscular antibiotics had been suggested as a prevention strategy but the evidence is scarce. Methods We conducted a cohort study by using Taiwan’s National Health Insurance Research Database (NHIRD) between 2000 and 2008. Patients received intramuscular benzathine pencillin 2.4 MU every 4 weeks at least three prescriptions within half a year were enrolled and followed for 1 year since the first dose. The prevention efficacy was determined by comparing the incidence of recurrent cellulitis in the prophylactic period to non-prophylactic period in each enrolled subject by a Poisson regression model. The prophylactic period was defined as 4 weeks after the date of each dose of benzathine penicillin injection and non-prophylactic period was the time not covered by penicillin during the follow-up period. Results In total, 211 patients were enrolled, including 123(58.3%) men. An average of 7.9 doses of IM benzathine penicillin was given in the study period. The incidence rate of recurrent cellulitis in the prophylactic period was 0.31 episode/patient-year, significantly lower than that of 0.77 episodes/patient-year in the non-prophylactic period (P = 0.004). The common underlying diseases of enrolled patients included diabetes mellitus (73, 35.4%), tinea pedis (69, 33.5%), impaired venous drainage (20, 9.7%), joint replacement of lower extremity (13, 6.3%) and edema status including congestive heart failure (19, 9.2%), chronic renal failure (15, 7.3%), and cirrhosis (8, 3.9%). In multivariate analysis of Poisson regression model, penicillin prophylaxis was associated with lower recurrence (relative risk (RR), 0.30; 95% confidence interval (CI), 0.13–0.69, P = 0.005), in contrast, impaired venous drainage (RR 2.78; CI, 1.20–6.48, P = 0.018) and tinea pedis (RR 3.04; CI, 1.17–7.90, P = 0.022) were associated with higher risk of recurrence. Conclusion The study was the largest cohort that demonstrated intramuscular injection of 2.4 million units benzathine penicillin with 4-week interval significantly reduced the incidence of recurrent cellulitis. Disclosures All authors: No reported disclosures.

Several tasks were tried to prepare crack-free mullite films on silica substrates. Basically, a sol containing TEOS (Tetraethylorthosilicate) and boehmite colloid was used for spin coating on silica substrate. The formulation of the sols was kept in stoichiometric composition 3Al2O3·2SiO2, or contained a crack-limiting agent, Polyvinylpyrrolidone (PVP). These films were then treated up to 1300°C. The properties of the sols and the dried films were characterized by rheometer, various thermal analysis techniques (DTA, TGA and TMA), also by XRD, SEM and TEM. The mullite film shows randomly oriented grains in sizes from 0.1 μm to a few micrometers. The films still contain fine θ- and δ-Al2O3 particles after being treated at 1280°C for 1 h.

Background and Purpose— This study was to evaluate the retrobulbar hemodynamics in patients who have transient monocular blindness (TMB) without carotid stenosis. Methods— Fifty-nine patients who have TMB without carotid stenosis were studied along with 59 age- and sex-matched controls. Color Doppler–imaging was used to study the retrobulbar hemodynamic by measuring the flow velocities (peak-systolic velocity, and end-diastolic velocity), vascular resistance indices (pulsatility index, and resistance index) in central retinal arteries, short posterior ciliary arteries, and ophthalmic arteries. The patients were divided into 2 groups according to the attack frequency: group 1 (occasional TMB, 2 or fewer attacks, 26 patients) and group 2 (frequent TMB, 3 or more attacks, 33 patients). Results— The risk factors for atherosclerosis were similar between the cases and controls. The means of end-diastolic velocity were significantly lower in central retinal arteries and ophthalmic arteries, and the pulsatility index and resistance index were significantly higher in all the 3 retrobulbar vessels in TMB patients than for the controls. The differences between patients and controls were greater for the group-2 patients. Conclusion— Patients who have TMB without carotid stenosis had altered retrobulbar hemodynamics with a generalized increase in vascular resistance in the retrobulbar arteries. The role of venous hypertension as an etiology needs further study.

Parkinson’s disease (PD) is the most common motor neurodegenerative disorder. Olfactory dysfunction is a prevalent feature of PD. It often precedes motor symptoms by several years and is used in assisting PD diagnosis. However, the cellular and molecular bases of olfactory dysfunction in PD are not known. The fruit fly Drosophila melanogaster, expressing human alpha-synuclein protein or its mutant, A30P, captures several hallmarks of PD and has been successfully used to model PD in numerous studies. First, we report olfactory deficits in fly expressing A30P (A30P), showing deficits in two out of three olfactory modalities, tested – olfactory acuity and odor discrimination. The remaining third modality is odor identification/naming. Second, oxidative stress is an important environmental risk factor of PD. We show that oxidative stress exacerbated the two affected olfactory modalities in younger A30P flies. Third, different olfactory receptor neurons are activated differentially by different odors in flies. In a separate experiment, we show that the odor discrimination deficit in A30P flies is general and not restricted to a specific class of chemical structure. Lastly, by restricting A30P expression to dopamine, serotonin or olfactory receptor neurons, we show that A30P expression in dopamine neurons is necessary for development of both acuity and discrimination deficits, while serotonin and olfactory receptor neurons appeared not involved. Our data demonstrate olfactory deficits in a synuclein fly PD model for exploring olfactory pathology and physiology, and for monitoring PD progression and treatment.

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S(2) mutant large HBV surface antigen (LHBS) in type II ground glass hepatocytes (GGHs) has been recognized as an emerging viral oncoprotein; it directly interacts with the c-Jun activation domain-binding protein 1 (JAB1) and subsequently causes hyperphosphorylation of the tumor-suppressor retinoblastoma and, consequently, leads to disturbed cell cycle progression. The interaction of the pre-S(2) mutant LHBS with JAB1 could provide a potential target for chemoprevention. In this study, we found that the preneoplastic type II GGHs showed a significant decrease of the cyclin-dependent kinase inhibitor p27(Kip1), which serves as a marker for pre-S(2) mutant-JAB1 complex formation. The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) elevated expression of the tumor-suppressor thioredoxin-binding protein 2 (TBP2), which subsequently enhanced the JAB1-TBP2 interaction and abolished the pre-S(2) mutant LHBS-induced degradation of p27(Kip1), which, in turn, recovered the normal cell cycle checkpoint. The pre-S(2) mutant LHBS-induced pro-oncogenic effects: increased cell proliferation, nuclear/cytoplasmic ratio and proliferating cell nuclear antigen expression, were all greatly ameliorated after SAHA treatments, which suggested SAHA as a promising chemopreventive agent for the pre-S(2) mutant oncoprotein-induced HCC. In conclusion, this study provides the mechanism of histone deacetylase (HDAC) inhibitor in preventing the pre-S(2) mutant-induced oncogenic phenotype. The HDAC inhibitor SAHA is therefore a potential chemopreventive agent for high-risk chronic HBV patients who may develop HCC.

The laser Doppler flowmeter has become an effective tool for the clinical study of microcirculation with non-invasive measurements and excellent velocity resolution. Microcirculation flow measurements cannot be used as reference criteria for circulation function. Thus, the relative change in fingertip microcirculation was measured through inflation and deflation of an automatic sphygmomanometer wrapped around the arm, and the blood pressure and functional parameters of circulation, such as biological zero (BZ), peak flow (PF) and time to peak flow (tp), were determined. For 50 healthy participants, the correlation coefficients for the laser Doppler flowmeter and oscillometric results were 0.950 and 0.838 for systolic and diastolic pressure, respectively. The mean and standard errors for both methods fell within the range specified in the Association for the Advancement of Medical Instrumentation standards. The BZ of an edema patient was about 5 times higher than normal. For patients with peripheral arterial occlusive disease (PAOD), the PF could not be determined, and the tp was about twice the normal value. The accuracy of blood pressure measurements using the laser Doppler flowmeter was comparable to that of the commonly used oscillometric sphygmomanometer, and the physiological circulation functional parameters were useful in identifying signs of edema and PAOD.

Background Patients with Parkinson’s disease (PD) are subject to posture instability and falling. However, PD was not included as one of the risk factors in commonly used fracture risk calculation tools and the fracture rate in patients with PD was rarely reported. The aim of this study was to evaluate the risk of hip fracture in patients with PD. Methods Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 394 patients with PD diagnosed in 1999–2000. The comparison cohort was comprised of 3940 age- and sex-matched patients from the same enrollment period. All patients were tracked from their index visits for eight years. Results Hip fracture developed in 10.4% of patients with PD and 4.1% of patients in the comparison cohort during the follow-up period. Log-rank test analysis showed a significantly higher rate of hip fracture in PD. The Cox proportional regression model showed an adjusted hazard ratio of 2.71 (95% confidence interval = 1.92–3.83, P Conclusion The hip fracture rate was as high as 10.4% in PD patients during 8 years follow-up period. While assessing the risk of hip fracture, PD should be taken into consideration. For those very high risk patients (elderly women with PD, osteoporosis, diabetes and diabetic neuropathy), many efforts should be made to prevent fracture.

Background and Purpose— The purpose of this study was to investigate the risk of future intracerebral hemorrhage development in patients with liver cirrhosis. Methods— Data were collected from the National Health Insurance Research Database of Taiwan. The study cohort included 948 patients with liver cirrhosis diagnosed in 1999 and 9480 age- and sex-matched patients of the same year. All patients were tracked from their index visits for 9 years. Results— Intracerebral hemorrhage developed in 1.3% of patients with liver cirrhosis and 1.0% of patients in the comparison cohort during the follow-up period. Log-rank test analysis showed no significant difference between the 2 cohorts ( P =0.39). A stratified Cox proportional regression model showed an adjusted hazard ratio of 1.62 (95% CI, 0.85 to 3.10) for patients with liver cirrhosis to develop intracerebral hemorrhage compared with patients without liver cirrhosis. Conclusions— Patients with liver cirrhosis had a similar intracerebral hemorrhage incidence rate but a trend of increased risk for intracerebral hemorrhage compared with the comparison cohort during the 9-year follow-up period.

Background: The purpose of this study is to investigate the epidemiology and medical expenses of Huntington’s disease (HD) in Taiwan. Methods: Cases of HD were identified from the National Health Insurance Research Database with corresponding International Classification of Diseases, Ninth Revision (ICD-9) code 333.4 from January 2000 to December 2007. Age- and sex-specific incidences were estimated by dividing the incidence number by population data obtained from the Department of Statistics, Ministry of the Interior. Results: During the study period, 182 cases were identified, including 81 males and 101 females. The average annual incidence rate was 0.1 per 100,000. The age-specific incidence peaked in the 40–49 age group in men (0.23 per 100,000 per year) and in the 50–59 age group in women (0.24 per 100,000 per year). The incidence rate was only 0.01 per 100,000 per year in those under 20 years of age. The prevalence was 0.42 per 100,000 in 2007. Conclusions: This is the first population-based epidemiologic study on HD in Taiwan. The incidence rates and prevalence were much lower than those of Caucasians although the age distribution was similar.

Cerebral venous outflow insufficiency via the internal jugular vein (IJV) is associated with several neurological disorders. However, a normal reference set of IJV hemodynamic parameters derived from a large, healthy population over a wide range of age has, until now, been lacking. Color-coded duplex sonography was performed on the IJVs of 349 subjects (55.60 ± 17.49,16 to 89 y; 167 M/182 F). With increasing age, increased lumen area and decreased time-averaged mean velocity of bilateral IJV and a decreased proportion of total flow volume, drainage in the left IJV were found. The frequency of left jugular venous reflux (JVR) also increased with aging. We report IJV hemodynamic parameters across a large population, which could be used as a normal reference for clinical and research purposes. Furthermore, we found a decreased proportion of venous drainage, increased JVR prevalence, dilated lumen and slowed flow velocity in the left IJV, all of which suggest increased left IJV outflow impedance with aging.

Eremofortin C (EC) and PR toxin are secondary metabolites of Penicillium roqueforti. Of 17 strains from the American Type Culture Collection that were studied for their ability to produce EC and PR toxin, 13 produced these metabolites. Toxin production by strains grown in solid media (10 cereals and 8 other agricultural products) was also investigated. Production of EC and PR toxin by fungi grown on cereals was greater than production of EC and PR toxin by fungi grown on legumes; fungi grown on corn produced the greatest amount of PR toxin. Addition of corn extracts to the culture medium greatly increased the production of EC and PR toxin in a coordinated manner, with no significant change in mycelial dry weight. The fungi produced the highest levels of EC and PR toxin at 20 to 24 degrees C depending on the strain. Toxin production was higher in stationary cultures than in cultures that were gently shaken at 120 rpm. The optimum pH for production of both EC and PR toxin was around pH 4.0. With regard to spore age, toxin levels did not change significantly when we used spores obtained from fungi that were grown at 24 degrees C for 3 up to 48 days.

Background: Adopting thrombolytic therapy with tissue plasminogen activator (tPA) in clinical practice presents many challenges. One major factor is the restrictive time window of 0–3 hours after symptom onset, for the commencement of treatment. Objective: To test the efficacy of a newly developed plasminogen activator (human tissue urokinase type plasminogen activator [HTUPA]) for the treatment of acute ischaemic stroke within 5 hours of symptom onset. Design: An open-label, dose escalation trial. The initial dose was 0.3 mg/kg and could be increased or decreased depending on tolerability. Setting: Three teaching hospitals in Taiwan. Participants: Thirty-three patients who presented with National Institute of Health Stroke Scale (NIHSS) scores of between 9 and 20, who had evidence of ischaemic stroke confirmed by CT. Main outcomes measures: Efficacy was assessed by the NIHSS, the Modified Rankin Scale (MRS), the Barthel Index and the Glasgow Outcome Scale. Preliminary efficacy endpoints included major neurological improvement at 24 hours and favourable outcome at 90 days after administration of HTUPA. Results: Of the 33 patients who received HTUPA, 29 received 0.3 mg/kg, 3 received 0.35 mg/kg and 1 received 0.4 mg/kg. Major neurological improvement, defined as improvement of ≥4 points on the NIHSS 24 hours after treatment, was observed in 45% of all patients treated (15/33) and in 48% (14/29) of those treated with 0.3 mg/kg. Ninety days after symptom onset, in those who received HTUPA 0.3 mg/kg, the proportion of patients with a favourable outcome was 34% on the NIHSS (≤1), 45% on the MRS (0 or 1), 41% on the Barthel Index (≥95) and 45% on the Glasgow Outcome Scale (1). Eighty six percent of the patients treated with 0.3 mg/kg within 0–3 hours of symptom onset reached scores of 0–1 on both the NIHSS and the MRS. Conclusions: Approximately 50% of patients treated with HTUPA 0.3 mg/kg within a 5-hour window after symptom onset experienced major neurological improvement within 24 hours of drug administration. Thrombolytic agents, in this case HTUPA, may be suitable for Taiwanese or Asian patients with acute ischaemic stroke who meet the inclusion criteria.