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BackgroundIschemic stroke poses a major threat to human health and represents the third leading cause of death worldwide and in Taiwan. Post-acute care (PAC) training has been reported to be beneficial for post-index stroke events. However, knowledge is still lacking on the outcome of stroke events with cardiac origin. The focus of the current study is to investigate the effectiveness of PAC in this subgroup of patients as well as identify key baseline pointers that are capable of early prediction of patients' physical recovery. In addition, the authors hypothesize that the routinely arranged non-invasive carotid duplex that evaluates the characteristics of the carotid lumen could play a significant role in providing an early outcome prediction.MethodsFor the current research, 142 ischemic stroke patients with underlying cardiac arrhythmia (atrial fibrillation) were retrospectively recruited. The patients' basic demographics, neuroimaging, carotid duplex, and basic biochemistry datasets were accurately documented. The pre and post-admission National Institutes of Health Stroke Scale (NIHSS) (6-month follow-ups), Barthel Index, and mRS score (12-month follow-ups) were also recorded. All statistical analyses were performed using R for Windows (version 3.6.3). Barthel Index, NIHSS, and mRS scores obtained before and after hospitalization were compared to determine the patients' outcomes and were classified as improved or unimproved. A multivariate logistic analysis was designed and applied to assess the significance of risk factors and to obtain the odds ratios (ORs). The receiver operating characteristic (ROC) curve and the Youden Index was used to find the important cut-off point information, and the area under the curve (AUC) was calculated to provide accuracy.ResultsThe average age of the 142 ischemic stroke patients enrolled in the current study was about 66 years, of which 88 patients were male and 54, female. Many of them had other comorbidities: 86 patients had mixed hyperlipidemia (60.56%), 115 had hypertension (80.99%), and 49 suffered from diabetes mellitus (34.51%). The mRS showed an improvement in the condition of only 40 patients (28.175%), whereas the Barthel Index showed improvement in 71 patients (50%), and 68 patients (47.89%) showed recovery on the NIHSS. The Barthel Index and NIHSS were selected because they already had an almost equal number of samples among the improved and unimproved groups (50%), rather than mRS, which had a lower number (28.17%) of improved cases. While conducting the EuroQol-5 Dimension (EQ-5D) assessment, anxiety/depression stood out as the most prominent issue, affecting 44 patients (30.99%). Self-care was another factor that was involved in the ongoing improvement of 36 patients (25.35%). Multivariate logistic analysis of both NIHSS and Barthel Index showed improvement with a contralateral plaque index statistical significance (P

Background and objectives: The objective of this study is to elucidate peripheral occlusion artery disease (PAOD) as a risk factor for cellulitis. Materials and Methods: This is a retrospective population-based cohort study. The database is the Longitudinal Health Insurance Database, which covers two million beneficiaries from the entire population of the 2010 registry for beneficiaries in Taiwan. The PAOD group is composed of patients who were newly diagnosed with PAOD from 2001 to 2014. The non-PAOD group is composed of patients who were never diagnosed with PAOD from 2001 to 2015. All patients were followed until the onset of cellulitis, death, or until the end of 2015. Results: Finally, 29,830 patients who were newly diagnosed with PAOD were included in the PAOD group, and 29,830 patients who were never diagnosed with PAOD were included in the non-PAOD group. The incidence densities (ID) of cellulitis were 26.05 (95% CI = 25.31–26.80) patients per 1000 person-years in the PAOD group and 49.10 (95% CI = 48.04–50.19) in the non-PAOD group. The PAOD group had an increased risk of cellulitis (adjusted HR = 1.94, 95% CI = 1.87–2.01) compared to the non-PAOD group. Conclusions: Patients with PAOD were associated with a higher risk of subsequent cellulitis compared to patients without PAOD.

Abstract Background DNA methylation of Cadherin 13 (CDH13), a tumor suppressor gene is associated with gene repression and carcinogenesis. We determined the relation of dietary fat and sex with CDH13 cg02263260 methylation in Taiwanese adults. Methods Data of 870 eligible participants (430 men and 440 women) between 30 and 70 years were obtained from the Taiwan Biobank (TWB) database. The association of dietary fat and sex with CDH13 cg02263260 methylation was determined using multiple linear regression. Results The association between sex and cg02263260 methylation was significant: beta-coefficient (β) = 0.00532; 95% confidence interval (CI) = 0.00195–0.00868. Moreover, the interaction between sex and dietary fat on cg02263260 methylation was significant (P-value = 0.0145). After stratification by sex, the association of dietary fat with cg02263260 methylation was significant only in women. Specifically, high dietary fat was positively associated with cg02263260 methylation in women (β = 0.00597; 95% CI = 0.00061–0.01133) and the test for trend was significant (P-value = 0.0283). Conclusion High fat intake was significantly associated with higher cg02263260 methylation in women and the test for trend was significant. These findings suggest that the association of fat intake and CDH13 cg02263260 might vary by sex and CDH13 cg02263260 methylation levels in women might increase as fat intake increases.

This study evaluated the association between long-term low-dose aspirin use and decreased risk of pneumonia in patients with cardio-cerebra-vascular ischemic diseases (CCVDs). This retrospective cohort study used records from Taiwan's National Health Insurance Research Database of claims made between 1997 and 2013. After propensity score matching (PSM), patients who took a low dose of aspirin for more than 90 days within 1 year of diagnosis with CCVDs were identified as the exposure group (n = 15,784). A matched total of 15,784 individuals without aspirin use were selected for the non-aspirin group. The main outcome was the development of pneumonia after the index date. Multivariable Cox regression analysis and Kaplan–Meier survival analysis were performed to estimate the adjusted hazard ratio (aHR) and cumulative probability of pneumonia. The result after PSM indicated a lower hazard ratio for pneumonia in aspirin users (aHR = 0.890, 95% confidence interval = 0.837–0.945). Therefore, patients with CCVDs who took aspirin had a lower risk of developing pneumonia than those who did not. In conclusion, this population-based cohort study demonstrated that long-term low-dose aspirin use is associated with a slightly decreased risk of pneumonia in patients with CCVDs.

Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of FGFR4 gene polymorphisms on the risk and progression of CRC. Three FGFR4 single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG; AOR, 0.236; p = 0.046) or rs351855 (GA and AA; AOR, 0.191; p = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression.

Background and objectives: We aimed to evaluate the correlation between periodontal disease (PD) and following ocular diseases via the National Health Insurance Research Database in Taiwan. Materials and Methods: A retrospective cohort study was conducted. Subjects were regarded as having PD according to the diagnostic codes. For comparison, each subject with PD was matched to one non-PD individual from the database after exclusion. The main outcome was defined as the development of infectious keratitis, endophthalmitis, orbital cellulitis, lacrimal duct infection, uveitis and infectious scleritis. Cox proportional hazard regression was used to yield the adjusted hazard ratios (aHR) of ocular diseases between the study and control groups. Results: A total of 426,594 subjects were enrolled in both the study and control groups. In the multivariable analysis, significantly higher rates of infectious keratitis (aHR: 1.094, 95% CI: 1.030–1.161), uveitis (aHR: 1.144, 95% CI: 1.074–1.218) and infectious scleritis (aHR: 1.270, 95% CI: 1.114–1.449) were found in the study group. Concerning the PD interval, infectious keratitis (aHR: 1.159, 95% CI: 1.041–1.291) and infectious scleritis (aHR: 1.345, 95% CI: 1.055–1.714) would significantly occur in PD patients with an interval shorter than two years, individuals with a PD interval that ranged from two to five years were under a higher risk of developing uveitis (aHR: 1.184, 95% CI: 1.065–1.315) and infectious scleritis (aHR: 1.386, 95% CI: 1.125–1.708), and the rate of uveitis (aHR: 1.149, 95% CI: 1.038–1.272) was significantly higher if PD persisted more than five years. Conclusions: The presence of PD was moderately associated with the risk of developing infectious keratitis, uveitis and infectious scleritis.

Background and objectives: Breast cancer is a common cancer in women and has been the fourth leading cause of death in Taiwanese women. Risk factors for breast cancer include family history of breast cancer, genetic factors, and not breastfeeding. Several studies have reported an association between repeated inflammation at a young age, especially among lactating women, and cancer; however, the number of studies about the association of mastitis and breast cancer in nonlactating women is still limited. Therefore, the aim of this study was to determine the relationship between mastitis in women aged ≥40 years and breast cancer. Materials and Methods: This was a retrospective cohort study design. The data source was the Longitudinal Health Insurance Database 2010 (LHID 2010), comprising data collected by Taiwan’s National Health Insurance program. Cases of newly diagnosed mastitis in women aged ≥40 years (ICD-9-CM code = 611.0) were selected from the years 2010 to 2012. Women not diagnosed with mastitis were selected as the control group, and their data for the years 2009 to 2013 were obtained through the database. In addition, the non-mastitis group was matched 1:10 by age. Results: A total of 8634 participants were selected from the LHID 2010, which included 734 cases with mastitis and 7900 cases without mastitis. After adjustment for age, hypertension, hyperlipidemia, diabetes, hypothyroidism, and autoimmune diseases, the Cox proportional hazard model showed that patients with mastitis had a higher risk of breast cancer (aHR = 3.71, 95% CI = 1.9–7.02) compared with the non-mastitis group. The Kaplan–Meier curve also showed that women with mastitis had a higher risk of developing breast cancer. Conclusions: This study confirmed that women with mastitis have a higher risk of developing breast cancer. Therefore, women aged ≥40 years could reduce breast cancer risk by taking precautions to prevent mammary gland infection and mastitis.

Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30−70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (β = −5.705; p = 0.001) followed by lacto-ovo vegetarians (β = −3.900; p < 0.001) and former vegetarians (β = −0.329; p = 0.475). The test for trend was significant (p < 0.001). After categorization by exercise modalities, the β-value was −13.984 for strict vegetarians, −4.419 for lacto-ovo vegetarians, and −1.864 for former vegetarians, respectively (p < 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.

BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk. METHODOLOGY/PRINCIPAL FINDINGS:Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC. After adjustment for potential confounders, patients with at least one T allele at rs11545028 of WWOX may have a significantly smaller tumor size, reduced levels of α-fetoprotein and alanine aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX conferred higher risk of vascular invasion. Additional in silico analysis also suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which in turn contributes to tumor vascular invasion. CONCLUSIONS:In conclusion, genetic variations in WWOX may be a significant predictor of early HCC occurrence and a reliable biomarker for disease progression.

Nuclear localization of β-catenin is known to associate with malignant transformation of many squamous cell carcinomas. The aim of this study was to compare β-catenin expression in normal human oral epithelium and areca quid chewing associated oral squamous cell carcinomas (OSCCs) and further to explore the potential mechanisms that may lead to induce β-catenin expression. Methods: A total of 40 areca quid chewing-associated OSCCs and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, extracellular signal-regulated protein kinase inhibitor PD98059, glutathione precursor N-acetyl-l-cysteine (NAC), tyrosine kinase inhibitor herbimycin-A, p38 inhibitor SB203580, and phosphatidylinositaol 3-kinase inhibitor LY294002 were added to find the possible regulatory mechanisms. Results: β-catenin expression was significantly higher in OSCC specimens than that in normal oral epithelial specimens (p

Invasive lobular cancer (ILC) tends to be significantly larger in size with significantly more positive lymph nodes, whereas ILC has a significantly more favorable outcome, compared to stage-matched invasive ductal carcinoma (IDC). The mechanism accounting for such differences remains elusive. Based on morphological, immunohistochemical, and molecular studies of over 1,000 cases of human breast cancers, we hypothesize that the differences may result from the structural and/or functional differences of their surrounding myoepithelial cell layers, which dictate lobular and ductal tumor cells to follow different pathways of invasion or metastasis. The background, rationale, supportive data, and implications of our hypothesis are presented and discussed.

Background: There is an upward trend for parents to resort to assisted reproductive technology (ART) treatment due to delayed childbirth or birth difficulties.Objective: This study investigates the pregnancy health and birth outcomes of women who underwent ART and analyzes the factors that influence birth weight to become

Chinese herbs have been and still are widely used as important remedies in Oriental medicine. Over the recent years, a variety of biologically active constituents have been isolated from these sources and confirmed to have multifunctional activity in experimental studies. Honokiol is a small-molecule polyphenol isolated from the genus Magnolia. It is accompanied by other related polyphenols, including magnolol, with which it shares certain biological properties. Recently, honokiol and magnolol have been found to have anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties in preclinical models, without appreciable toxicity. These findings have increased interest in bringing honokiol and magnolol to the clinic as novel therapeutic agents in dermatology. In this review, the findings concerning the major mechanisms of action of honokiol and magnolol are described. Knowledge of the multiple activities of honokiol and magnolol can assist with the development of honokiol and magnolol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol and magnolol in the patient setting for dermatologic disorders.

Human breast cancer represents a group of highly heterogeneous lesions consisting of about 20 morphologically distinct subtypes with substantially different molecular and/or biochemical signatures, clinical courses, and prognoses. This study analyzed the possible correlation between the morphological presentations of breast cancer and two hypothesized models of carcinogenesis, in order to identify the intrinsic mechanism(s) and clinical implications of breast cancer heterogeneity.

Our previous studies revealed that pregnancy associated breast cancer (PABC) had significantly reduced nuclear p63 expression in myoepithelia, while intense cytoplasmic p63 expression in associated epithelia. Our current study assessed these epithelia using immunohistochemistry with a panel of aggressiveness and invasiveness related markers and comparative genomic hybridization (array-CGH) with over 30,000 DNA probes. These epithelia showed several unique alterations, including (1) immunohistochemical and morphological resemblance to invasive cancer, (2) significant gain in copy numbers of DNA coding genes for morphogenesis, angiogenesis, and metastasis, and (3) significant loss in copy numbers of DNA coding genes for tumor suppressors, cell adhesion, and macromolecular complex assembly or intra-cellular trafficking. Detected array-CGH alterations correlated well with in vivo expression of a number of corresponding proteins tested. These findings suggest that aberrant sub-cellular localization of p63 expression in normal or hyperplastic appearing epithelial cells may significant contribute to increased invasiveness and aggressiveness of these cells.

The fractional concentration of exhaled nitric oxide (FENO) has been reported to be elevated in asthma and many other lung diseases. The present study investigated reference values and determinants of FENO in a Taiwanese non-smoking, healthy adult population. Methods: We used a chemiluminescence analyzer according to American Thoracic Society/European Respiratory Society recommendations to measure FENO values in 356 adults who received a health check-up and a detailed respiratory questionnaire at Taichung Veterans General Hospital, Taiwan. Among the volunteers, 249 fulfilled our definition of healthy adults: no history of smoking or physician-diagnosed asthma; no recent upper airway infection; no chronic respiratory symptoms; and no allergic rhinitis and urticaria. Results: Among the 249 non-smoking and non-asthmatic adults, the mean (5th to 95th percentile reference range) FENO was 27.9 (12.5–58.0) parts per billion. In multivariate regression analyses, age and lung function (forced vital capacity or forced expiratory volume in 1 second) were associated positively with FENO values. Sex, height, weight, and ambient NO values were not associated significantly with FENO values. Conclusion: Age and lung function were predictors of FENO in this population, and these factors should be considered for clinical applications of FENO measurements.

Heme oxygenase-1 (HO-1) is known as an oxidative stress responsive protein that is upregulated by various physiologic and endogenous stimuli. HO-1 has been proposed to provide an important cellular response that protects cells against oxidative damage. Areca quid chewing is a major risk factor in the development and further progression of oral squamous cell carcinoma (OSCC). The aim of the present study was to investigate the difference in HO-1 expression in normal human oral epithelium and OSCC, and further explore the potential mechanism that may lead to HO-1 expression. Methods: Thirty-five OSCC and 10 normal epithelium specimens were examined by immunohistochemistry and analyzed by clinicopathologic profiles. The oral epithelial GNM cell line was challenged with arecoline, a major areca nut alkaloid, by reverse-transcriptase polymerase chain reaction. Furthermore, tobacco smoke carcinogen benzo[a]pyrene (BaP) and glutathione (GSH) precursor N-acetyl-L-cysteine were added to find the possible regulatory mechanisms. Results: HO-1 expression was significantly higher in OSCC specimens (p < 0.05). No significant difference in HO-1 expression was observed with respect to age, sex, T category, and stage (p > 0.05). The high HO-1 expression was associated with lymph node metastasis (p = 0.005). In addition, arecoline was found to elevate HO-1 mRNA in a dose-dependent manner (p < 0.05). The addition of BaP enhanced arecoline-induced HO-1 expression (p < 0.05). Moreover, addition of NAC markedly inhibited arecoline-induced HO-1 expression (p < 0.05). Conclusion: Taken together, these results suggest that HO-1 expression is significantly upregulated in OSCC from areca quid chewers, and arecoline may be responsible for enhanced HO-1 expression in vivo. The compounds of cigarette smoke may act synergistically in the pathogenesis of areca-quid-chewing-associated OSCC. The regulation of HO-1 expression induced by arecoline is critically dependent on intracellular GSH concentration.

Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of osteoarthritis (OA). Here, we investigated the intracellular signaling pathways involved in CCL2-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human OA synovial fibroblasts (OASFs).Stimulation of OASFs with CCL2 induced VCAM-1 expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor (RS102895), PKCδ inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 increased PKCδ and p38MAPK activation. Treatment of OASFs with CCL2 also increased the c-Jun phosphorylation and c-Jun binding to the AP-1 element on the VCAM-1 promoter. Moreover, CCL2-mediated CCR2, PKCδ, p38MAPK, and AP-1 pathway promoted the adhesion of monocytes to the OASFs monolayer.Our results suggest that CCL2 increases VCAM-1 expression in human OASFs via the CCR2, PKCδ, p38MAPK, c-Jun, and AP-1 signaling pathway. The CCL2-induced VCAM-1 expression promoted monocytes adhesion to human OASFs.

BACKGROUND: Angiogenesis is essential for the progression of osteoarthritis (OA). Hepatocyte growth factor (HGF) is an angiogenic mediator, and it shows elevated levels in regions of OA. However, the relationship between HGF and vascular endothelial growth factor (VEGF-A) in OA synovial fibroblasts (OASFs) is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that stimulation of OASFs with HGF induced concentration- and time-dependent increases in VEGF-A expression. Pretreatment with PI3K inhibitor (Ly294002), Akt inhibitor, or mTORC1 inhibitor (rapamycin) blocked the HGF-induced VEGF-A production. Treatment of cells with HGF also increased PI3K, Akt, and mTORC1 phosphorylation. Furthermore, HGF increased the stability and activity of HIF-1 protein. Moreover, the use of pharmacological inhibitors or genetic inhibition revealed that c-Met, PI3K, Akt, and mTORC1 signaling pathways were potentially required for HGF-induced HIF-1α activation. CONCLUSIONS/SIGNIFICANCE: Taken together, our results provide evidence that HGF enhances VEGF-A expression in OASFs by an HIF-1α-dependent mechanism involving the activation of c-Met/PI3K/Akt and mTORC1 pathways.

Low high-density lipoprotein cholesterol (HDL-C) is a major risk factor for cardiovascular diseases (CVDs), the leading cause of global mortality. We aimed to determine the effect of coffee drinking and sex and their interaction, as well as rs1800588 and rs1800775 polymorphisms on HDL-C levels in Taiwanese adults. Data of 4262 men and 4813 women, aged 30–70 years, were retrieved from Taiwan Biobank. The interaction between sex and coffee drinking on HDL-C was significant (p = 0.0452). Coffee consumption was significantly associated with higher HDL-C levels in only women (β = 0.81679; p = 0.0246). However, rs1800588 and rs1800775 variants were significantly associated with HDL-C in both sexes. In women, β-values were 0.99080; p = 0.0059 and 3.16277; p < 0.0001 for rs1800588 CT and TT genotypes, respectively and −1.80954; p < 0.0001 and −2.81512; p < 0.0001 for rs1800775 AC and CC genotypes, respectively. In men, β-values were 1.32430; p < 0.0001 and 3.24976; p < 0.0001 for rs1800775 CT and TT genotypes, respectively and −1.96232; p < 0.0001 and −2.71536, p < 0.0001 for the AC and CC genotypes, respectively. In conclusion, coffee drinking was significantly associated with higher high-density lipoprotein (HDL) levels in women but not men after adjusting for confounders including rs1800588 (LIPC) and rs1800775 (CETP) variants. [ABSTRACT FROM AUTHOR]

Objectives: Isolated minor rib fractures (IMRFs) after blunt chest traumas are commonly observed in emergency departments. However, the relationship between IMRFs and subsequent pneumonia remains controversial. This nationwide cohort study investigated the association between IMRFs and the risk of pneumonia in patients with blunt chest traumas. Design: Nationwide population-based cohort study. Setting: Patients with IMRFs were identified between 2010 and 2011 from the Taiwan National Health Insurance Research Database. Participants: Non-traumatic patients were matched through 1:8 propensity-score matching according to age, sex, and comorbidities (namely diabetes, hypertension, cardiovascular disease, asthma and chronic obstructive pulmonary disease (COPD)) with the comparison cohort. We estimated the adjusted HRs (aHRs) by using the Cox proportional hazard model. A total of 709 patients with IMRFs and 5672 non-traumatic patients were included. Main outcome measure: The primary end point was the occurrence of pneumonia within 30 days. Results: The incidence of pneumonia following IMRFs was 1.6% (11/709). The aHR for the risk of pneumonia after IMRFs was 8.94 (95% CI=3.79 to 21.09, p<0.001). Furthermore, old age (≥65 years; aHR=5.60, 95% CI 1.97 to 15.89, p<0.001) and COPD (aHR=5.41, 95% CI 1.02 to 3.59, p<0.001) were risk factors for pneumonia following IMRFs. In the IMRF group, presence of single or two isolated rib fractures was associated with an increased risk of pneumonia with aHRs of 3.97 (95% CI 1.09 to 14.44, p<0.001) and 17.13 (95% CI 6.66 to 44.04, p<0.001), respectively. Conclusions: Although the incidence of pneumonia following IMRFs is low, patients with two isolated rib fractures were particularly susceptible to pneumonia. Physicians should focus on this complication, particularly in elderly patients and those with COPD. [ABSTRACT FROM AUTHOR]

Oral cancer is a common cancer with poor prognosis. We evaluated the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) and its prognostic significance in oral cancer. PBK/TOPK expression was measured by immunohistochemical staining of samples from 287 patients with oral cancer. The association between PBK/TOPK expression and clinicopathological features was analyzed. The prognostic value of PBK/TOPK for overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. A high PBK/TOPK expression level was correlated with long overall survival. The prognostic role of PBK/TOPK expression was significant in young patients (p < 0.05), patients with smoking habits (p < 0.05), and late stage disease (p < 0.05). Our results suggest that PBK/TOPK expression is enhanced in oral cancer. High PBK/TOPK expression, either alone or in subgroups according to clinicopathological features, may serve as a favorable prognostic marker for patients with oral cancer. [ABSTRACT FROM AUTHOR]

(2011) Journal of Nursing Management , 339-345 To compare the symptoms of fatigue and physiological indices in nurses who work during the day with nurses who work in shifts. One-hundred and seven nurses were recruited and asked to assess their symptoms of fatigue before their work commenced and after it finished. Using logistic regression analysis adjusted for covariates, it was found that nurses who work in shifts were more fatigued than nurses who work during the day (odds ratio = 2.44, P < 0.10). There was a significant difference regarding critical flicker fusion in the two groups of nurses ( P = 0.032), and nurses who work in shifts had poorer physiological indices than nurses who work during the day. It is clear that differing work schedules result in differing levels of fatigue, with shift work attributing to higher levels than day work. Nurse managers need to take into account the fatiguing effects of different work schedules when designing rostering patterns. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide. Genetic polymorphism has been reported as a predictive factor related to a higher risk for HCC. Because the stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, have been reported to play important roles in tumor cell proliferation, angiogenesis, and metastasis of HCC, the aim of this study was to estimate the relationship between SDF-1 and CXCR4 gene variants to HCC risk and clinicopathological status. Methods: Polymerase chain reaction-restriction fragment length polymorphism was used to measure SDF-1 (rs1801157) and CXCR4 (rs2228014) gene polymorphisms in 311 healthy controls and 102 patients with HCC. Results: Compared to controls, individuals with at least one A allele had a higher risk of 1.57-fold (95% CI: 1.00–2.47) to induce HCC and had a risk of 2.81-fold (95% CI: 1.04–7.58) to develop a status of stage III or stage IV disease, after being adjusted for other confounders. However, there was no significant association between CXCR4 gene polymorphism and either HCC risk or pathological status. Additionally, both gene polymorphisms were not associated with the serum expression of liver-related clinical pathological markers. Conclusions: SDF-1–3′A gene polymorphism could be considered as a factor related to an increased susceptibility to the risk and pathological development of HCC. Clin Chem Lab Med 2009;47:412–8. [ABSTRACT FROM AUTHOR]

Human dihydrolipoamide dehydrogenase (hE3) is a common component of α-ketoacid dehydrogenase complexes. Mutations of this homodimeric protein cause E3 deficiency and are always fatal. To investigate its reaction mechanism, we first performed multiple sequence alignment with other 17 eukaryotic E3s. According to hE3 structure and the result of multiple sequence alignment, two amino acids, T148 and R281, were subjected to mutagenesis and four hE3 mutants, T148G, T148S, R281N, and R281K, were expressed and assayed. The specific activities of T148G, T148S, R281N, and R281K are 76.34%, 88.62%, 12.50%, and 11.93% to that of wild-type E3, respectively. The FAD content analysis indicated that the FAD content of these mutant E3s were about 71.0%, 92%, 96%, and 93% that of wild-type E3, respectively. The molecular weight analysis showed that these three mutant proteins form the dimer. Kinetic data demonstrated that the Kcat of forward reaction of all mutants, except T148 mutants, were decreased dramatically. The results of kinetic study suggest that T148 is not important to E3 catalytic function and R281 play a role in the catalytic function of the E3. [ABSTRACT FROM AUTHOR]

Rhinosinusitis is a common complication in patients with nasopharyngeal carcinoma (NPC) who receive radiotherapy. An impaired mucociliary clearance due to this treatment may be the major cause of rhinosinusitis in these irradiated patients. The relative frequency with which various pathogens cause rhinosinusitis in these patients is unknown. This study investigates the bacteriology of acute rhinosinusitis in irradiated NPC patients by maxillary sinus puncture. From October 2001 through July 2006, 20 irradiated NPC patients with radiograph-proven acute maxillary sinusitis received maxillary sinus punctures. Aspirate contents of the sinuses were collected for aerobic and anaerobic cultivation. A total sampling of 26 sides was performed in the 20 patients. The culture rate was 85%. Frequently identified aerobes and facultative anaerobes included alpha-hemolytic streptococcus ( n = 8), Staphylococcus aureus ( n = 5) and Pseudomonas aeruginosa ( n = 3). Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, however, are far less common. This may provide important information about the antibiotic therapy in irradiated NPC patients with acute rhinosinusitis. [ABSTRACT FROM AUTHOR]

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G) have been recommended for evaluating function and disability in patients with ankylosing spondylitis (AS). The aim of this study was to develop a Chinese version of the BASDAI, BASFI, and BAS-G and assess their reliability and validity. The Chinese version was obtained after a translation and back-translation process. A total of 447 patients with adult and juvenile AS were assessed using these three instruments. Reliability was tested by internal consistency and test–retest reliability. Internal consistency of the instrument was given as Cronbach’s alpha. Test–retest reliability was assessed by intraclass correlation coefficient. To assess the sensitivity to change, 153 patients were included in an 8-week follow-up study. In our analysis, the reliability of these three instruments—the BASDAI, BASFI, and BAS-G—for a 24-h test–retest showed acceptable intraclass correlation coefficients (0.92–0.94). Our Chinese versions of the BASDAI, BASFI, and BAS-G also showed 0.87, 0.94, and 0.90, respectively, with Cronbach’s alpha coefficient, indicating good reliability. For sensitivity to change in 8-week follow-up, all three instruments showed 5.0 to 5.4% changes. Our Chinese versions of the BASDAI, BASFI, and BAS-G showed adequate reliability, validity, and responsiveness to clinical change. Thus, disease activity and functional status in Chinese-speaking patients with AS may be adequately evaluated with these versions of the original instruments. [ABSTRACT FROM AUTHOR]

Aim: Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. The aim of the present study was to investigate the effect of alendronate, a bisphosphonate, on the invasion and migration of human chondrosarcoma cells (JJ012). Methods: JJ012 cells were treated with alendronate of various concentrations up to 100 μmol/L for a specified period, and then gelatin zymography and matrigel invasion assay was performed to study the effects of alendronate on matrix metalloproteinase (MMP)-2 activity and the invasion ability of JJ012 cells, respectively. Results: Our data showed that alendronate exerted a dose- and time-dependent inhibitory effect on the invasion and migration of JJ012 cells. Furthermore, gelatin zymography and RT-PCR showed that alendronate treatment decreased the activity and mRNA levels of MMP-2 in a concentration-dependent manner. Conclusion: Our findings suggest that alendronate may reduce MMP-2 secretion at the transcriptional and translational levels, and inhibit the invasion of chondrosarcoma cell. Therefore, alendronate may be a potential candidate for the systemic therapy of chondro-sarcomas, as well as other malignant diseases. [ABSTRACT FROM AUTHOR]

In Taiwan, colorectal cancer has one of the highest rates of increased incidence in the past two decades. Heterocyclic amines from dietary cooked meats are metabolically activated by NAT2 (N-acetyltransferase 2), which are associated with colorectal cancer incidence. Thus, the NAT2 fast acetylator genotype may be associated with colorectal cancer risk. However, the association between the NAT2 genotype and colorectal cancer risk is not clearly understood. We conducted a study with 244 primary colorectal cancer cases and 299 cancer-free healthy control subjects to verify the association of NAT2 polymorphisms with the risk of Taiwanese colorectal cancer. Our data showed that subjects with the NAT2 W/W homozygous genotype had a 1.63-fold increased risk of colorectal cancer compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.03–2.58); however, no risk was found in the W/Mx heterozygous and Mx/W+W/W fast acetylator genotypes. Being stratified by gender factors, the colorectal cancer risk in females with homozygous W/W or Mx/W+W/W fast acetylators increased 2.47-fold and 2.13-fold compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.27–4.82 for W/W genotype; 95 percent confidence interval, 1.17–3.89 for Mx/W+W/W genotype); however, the risk of the NAT2 genotype and colorectal cancer was not observed in males. Collectively, patients with the NAT2 fast acetylator genotype were more prone to colorectal cancer and reflected the possibility that exposure to heterocyclic amines may contribute to colorectal cancer development in Taiwan, especially in Taiwanese females. [ABSTRACT FROM AUTHOR]

Fourteen serum samples obtained from hepatitis B virus (HBV) chronic carriers and patients recovered from hepatitis B infection were used with four sodium dodecyl sulfate‐treated enzyme‐linked immunosorbent assay (ELISA) plates available commercially, and one self‐prepared HBcAg analog for evaluation of anti‐HBe subclass pattern absorbance. The self‐prepared plates had the best performance and were thus used for samples obtained from 104 (60 male and 44 female) HBV chronic carriers and 439 (247 male and 192 female) recovered individuals. Tests for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also carried out in 21 of the subjects (>25 IU/ml). Statistical comparison of these patients with elevated ALT/AST levels with other ALT/AST‐normal chronic carriers revealed no significant differences in the anti‐HBe OD, although the mean optical density (OD) of patients with elevated ALT/AST levels was higher. The results suggest that the anti‐HBe IgG subclass profiles in the chronic carriers did not change with inflammation of the liver, and were independent of sex and age. In contrast to previous anti‐HBc findings, the distribution pattern of anti‐HBe subclasses in HBV chronic carriers was IgG1 > IgG4 > IgG3 while in the recovered individuals it was IgG1 > IgG3 > IgG4, for both males and females. Subclasses IgG1 and IgG2 were the most and least prevalent isotypes, respectively, in both study groups. The results of the study suggest that induction of IgG1 and/or IgG3 antibodies is important for effective virus neutralization, while IgG2 antibodies are of limited importance. Significantly higher OD values for anti‐HBe IgG4 were observed when comparing samples from the chronic carriers and recovered individuals, which may reflect the effects of persistence. Further, in contrast to previous anti‐HBs results, the concentrations of total IgG and IgG1 were higher in the samples from chronic carriers relative to those from recovered individuals. J. Med. Virol. 79:495–502, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For those patients with plasma Hcy ≥15 μmol/l, a perspective trial of daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4±3.8 μmol/l, p<0.05), MTX (11.9±4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2±2.6, p<0.05) compared with normal controls (8.6±1.2 μmol/l) and AS patients without DMARD(9.4± 2.6μmol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg can lower Hcy level in 2 weeks (32.3±24.0 vs 15.6±11.1 μmol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence of nocturnal enuresis among children in elementary school in Taiwan and to evaluate its associated factors and severity. Materials and Methods: A randomly selected cross-sectional study was conducted from elementary schools in Changhua county, Taiwan in 2003. In all, 9228 questionnaires were sent to 46 schools in 26 districts. Results: A total of 92.1% (8496/9228) of questionnaires were completed. The overall prevalence of nocturnal enuresis was 6.8%. The ratio of male to female was about 1.5 (8.0% vs. 5.5%). The prevalence of enuresis according to age group declined from 12.5% at 6 years to 2.0% at 12 years. The prevalence of enuresis in the urban area did not show significant difference from that of rural area (6.2% vs. 6.9%). Of the factors associated with enuresis, gender, age, urinary frequency or urgency, heredity, drinking habit before sleep and difficulty in waking showed significant difference after multiple logistic regression analysis. After multivariate analysis, difficulty in waking and time of wetting were the only factors significantly associated with the severity of enuresis. Conclusion: Our investigation showed the prevalence of enuresis is similar to those reports from the north of Taiwan and most of other western countries, but higher than that of China and Hong-Kong. Difficulty in waking and time of wetting were the only factors significantly associated with the severity of enuresis. [ABSTRACT FROM AUTHOR]

PURPOSE The purpose of this study was to evaluate function of major salivary glands, subjective xerostomia, and correlation between subjective and objective xerostomia scoring after precision-oriented radiotherapy for nasopharyngeal carcinoma. MATERIALS AND METHODS From 2000 to 2002, 34 patients with histologically proven non-metastatic nasopharyngeal carcinoma received definitive therapy by parotid-sparing radiotherapy, which included intensity-modulated radiotherapy (33 patients > 60 Gy), 3D-conformal radiotherapy, and brachytherapy boost. Salivary function was assessed by sialoscintigraphy pre-irradiation and post-irradiation at 1, 6, 12, and 18 months. The salivary stimulated secretion ratio (SSR) was used to evaluate function of submandibular and parotid glands. Subjective and objective xerostomia was monitored by the LENT/SOMA system. RESULTS The median dose to parotid gland was 34.6 Gy (interquartile range, 32.9 36.5 Gy). The median dose to submandibular gland was 60.5 Gy (interquartile range, 58.1-61.5 Gy). Parotid-gland post-irradiation median SSR at 1 (0.01, P = 0.000) and 6 (0.08, P = 0.002) months showed significant reduction compared with pre-irradiation data (0.30). After 12 months, parotid-gland median SSR (12 months. 0.22, P = 0.734; 18 months, 0.16, P = 0.885) lost significance compared with pre-irradiation data. Submandibular-gland post-irradiation median SSR at 1 (P = 0.000), 6 (P = 0.000), 12 (P = 0.000), and 18 (P = 0.000) months all showed significant reduction compared with pre-irradiation data. There were significant correlations between LENT/SOMA subjective and objective xerostomia scores at 6 months (r = 0.657, P = 0.000), 12 months (r = 0.480, P = 0.013), and 18 months (r = 0.591, P = 0.002). CONCLUSIONS With parotid-sparing radiotherapy for nasopharyngeal carcinoma, gland function can recover significantly 12 months after radiotherapy. There were significant rank-order correlations between LENT/SOMA subjective and objective (analytic) grading scores at 6 to 18 months' follow up. [ABSTRACT FROM AUTHOR]

Although allergic asthma and allergic rhinitis have recently been considered to be a single disease, many questions remain unanswered. Why do some atopic patients develop asthma symptoms and others develop allergic rhinitis symptoms? Which factors play a role in the development of different allergic phenotypes? We hypothesized that angiotensin-converting enzyme (ACE) gene polymorphism might play a role in the development of asthma phenotypes in children with allergic rhinitis. The study sample included 106 children with allergic rhinitis, but no asthma, and 105 age- and gender-matched children with allergic rhinitis and asthma. Subjects of both groups exhibited the same systemic immunologic changes and allergen sensitivities. Controls consisted of 102 healthy children. The ACE genotype was determined by polymerase chain reaction. The serum total immunoglobulin E (IgE) level, allergen-specific IgE sensitivity, and eosinophil count were also measured. The frequencies of the DD genotype were significantly higher in the children with both allergic rhinitis and asthma than in the children with allergic rhinitis but no asthma [p = 0.018; odds ratio (OR) = 3.257; (1.222–8.680)]. Results of this study suggest that ACE gene polymorphism DD genotype might play a role in the development of the asthma phenotype in children with allergic rhinitis. [ABSTRACT FROM AUTHOR]

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6–12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus ( D.p.)/ D. farinae ( D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies. [ABSTRACT FROM AUTHOR]

Background: Etanercept (Enbrel), was the first approved biologics in Taiwan for rheumatoid arthritis (RA), juvenile RA (JRA), psoriatic arthritis and ankylosing spondylitis. Approximately 500 patients with RA were under etanercept therapy by April 2006. Aim: We aimed to review the current status of biological agents use in the treatment of rheumatic diseases in Taiwan. Methods: MEDLINE database (January 1966 to February 2006) was searched by MeSH terms, limited to Taiwan by author affiliations. All known principal clinical investigators and pharmaceutical companies in Taiwan were contacted for unpublished information about this issue. Results: Six articles including two clinical trials, two case series and two preclinical studies were found in MEDLINE since January 1966. A 12-week double-blind placebo-controlled study of 58 patients with active adult RA in Taiwan revealed better efficacy than results in Western countries. For JRA, two studies reported good results in polyarticular type JRA but fair response in systemic type. Adalimumab (Humira, Abbott) and Alefacept (Ameviev, Biogen) had completed their local trials in RA and psoriasis but they are not yet available in Taiwan. Widespread usage of biologics has been limited due to restricted insurance coverage policy only to the refractory patients with RA. Some herbs demonstrating TNF-α inhibition properties are under exploratory clinical trials. Conclusions: Etanercept showed better efficacy in patients with adult RA in Taiwan than Western countries. Some herbs demonstrated TNF-α inhibition and are under laboratory and clinical investigations. [ABSTRACT FROM AUTHOR]