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Objective This study investigated the psychological impact on, coping behaviors of, and traumatic stress experienced by healthcare workers during the early stage of the COVID-19 pandemic and formulated effective support strategies that can be implemented by hospitals and government policymakers to help healthcare staff overcome the pandemic. Methods This cross-sectional study recruited clinical healthcare workers at a regional hospital in Nantou County, Taiwan. The questionnaire collected personal characteristics, data on the impact and coping behaviors of the pandemic, and Impact of Event Scale-Revised (IES-R). A total of 354 valid questionnaires were collected. The statistical methods employed were univariate and multivariate stepwise regression, and logistic regression. Results Perceived impact and coping behaviors were found to be moderate in degree, and traumatic stress was lower than that in other countries. However, our data identified the following subgroups that require special attention: those with young age, those living with minor children, nurses, those with self-rated poor mental health, and those with insufficient COVID-19-related training. Conclusion Managers should pay particular attention to helping healthcare workers in high-risk groups, strengthen COVID-19 training, provide adequate protective equipment and shelter, and offer psychological counseling.

Background To identify predictors of carotid artery stenosis (CAS) progression in head and neck cancer (HNC) patients after radiation therapy (RT). Methods We included 217 stroke-naïve HNC patients with mild carotid artery stenosis after RT in our hospital. These patients underwent annual carotid duplex ultrasound (CDU) studies to monitor CAS progression. CAS progression was defined as the presence of ≥50% stenosis of the internal/common carotid artery on follow-up CDU. We recorded total plaque score (TPS) and determined the cut-off TPS to predict CAS progression. We categorized patients into high (HP) and low plaque (LP) score groups based on their TPS at enrolment. We analyzed the cumulative events of CAS progression in the two groups. Results The TPS of the CDU study at enrolment was a significant predictor for CAS progression (adjusted odds ratio [aOR] = 1.69, p = 0.002). The cut-off TPS was 7 (area under the curve: 0.800), and a TPS ≥ 7 strongly predicted upcoming CAS progression (aOR = 41.106, p = 0.002). The HP group had a higher risk of CAS progression during follow-up (adjusted hazard ratio = 6.15; 95% confident interval: 2.29–16.53) in multivariable Cox analysis, and also a higher trend of upcoming ischemic stroke (HP vs. LP: 8.3% vs. 2.2%, p = 0.09). Conclusions HNC patients with a TPS ≥ 7 in any CDU study after RT are susceptible to CAS progression and should receive close monitoring within the following 2 years.

BackgroundLittle is known about the effects of anticoagulation in patients with atrial fibrillation (AF) and left atrial enlargement (LAE).MethodsData of patients with AF were retrieved from Chang Gung Research Database during 2007–2016. We excluded patients who were not using oral anticoagulants, used anticoagulants for ResultsWe identified 40,777 patients who received a diagnosis of AF. After the exclusion criteria were applied, 6,445 patients remained, 4,922 with LAE, and they were followed up for 2.4 ±1.9 years. The mean age of the patients was 77.32 ± 0.18 in the NOAC group and 76.58 ± 6.91 in the warfarin group (p< 0.0001); 48.24% of patients in the NOAC group and 46.98% of patients in the warfarin group were men (p> 0.05). The mean CHA2DS2-VASc score was 3.26 ± 1.05 in the NOAC group and 3.07 ± 1.12 in the warfarin group (p< 0.0001). The mean HAS-BLED score was 3.87 ± 3.81 in the NOAC group and 3.86 ± 3.80 in the warfarin group (p> 0.05). Furthermore, the mean LA diameter was 4.75 ± 0.63 cm in the warfarin group and 4.79 ± 0.69 cm in the warfarin group (p> 0.05). Among patients with LAE, NOAC was associated with significantly reduced IS/SE events (CRR = 0.63, 95% CI = 0.52–0.77), no difference in major bleeding (CRR = 0.91, 95% CI = 0.78–1.05), and significantly reduced death from any cause (aHR = 0.65, 95% CI = 0.52–0.80) compared with warfarin.ConclusionsIn elderly patients with AF and LAE, NOAC was associated with reduced IS/SE and death from any cause compared with warfarin, whereas no difference in major bleeding was observed between these treatments.

The existing tamper detection schemes for absolute moment block truncation coding (AMBTC) compressed images are able to detect the tampering. However, the marked image qualities of these schemes can be enhanced, and their authentication methods may fail to detect some special tampering. We propose a secure AMBTC tamper detection scheme that preserves high image fidelity with excellent detectability. In the proposed approach, a bit in bitmaps of AMBTC codes is sequentially toggled to generate a set of authentication codes. The one that causes the least distortion is embedded into the quantization levels with the guidance of a key-generated reference table (RT). Without the correct key, the same reference table cannot be constructed. Therefore, the proposed method is able to detect various kinds of malicious tampering, including those special tampering techniques designed for RT-based authentication schemes. The proposed method not only offers better image quality, but also provides an excellent and satisfactory detectability as compared with previous works.

Background During the COVID-19 surge in Taiwan, the Far East Memorial Hospital established a system including a centralized quarantine unit and triage admission protocol to facilitate acute care surgical inpatient services, prevent nosocomial COVID-19 infection and maintain the efficiency and quality of health care service during the pandemics. Materials and methods This retrospective cohort study included patients undergoing acute care surgery. The triage admission protocol was based on rapid antigen tests, Liat® PCR and RT-PCT tests. Type of surgical procedure, patient characteristics, and efficacy indices of the centralized quarantine unit and emergency department (ED) were collected and analyzed before (Phase I: May 11 to July 2, 2021) and after (Phase II: July 3 to July 31, 2021) the system started. Results A total of 287 patients (105 in Phase I and 182 in Phase II) were enrolled. Nosocomial COVID-19 infection occur in 27 patients in phase I but zero in phase II. More patients received traumatological, orthopedic, and neurologic surgeries in phase II than in phase I. The patients’ surgical risk classification, median total hospital stay, intensive care unit (ICU) stay, intraoperative blood loss, operation time, and the number of patients requiring postoperative ICU care were similar in both groups. The duration of ED stay and waiting time for acute care surgery were longer in Phase II (397 vs. 532 minutes, p < 0.0001). The duration of ED stay was positively correlated with the number of surgical patients visiting the ED (median = 66 patients, Spearman’s ρ = 0.207) and the occupancy ratio in the centralized quarantine unit on that day (median = 90.63%, Spearman’s ρ = 0.191). Conclusions The triage admission protocol provided resilient quarantine needs and sustainable acute care surgical services during the COVID-19 pandemic. The efficiency was related to the number of medical staff dedicated to the centralized quarantine unit and number of surgical patients visited in ED.

Background Transcatheter aortic valve-in-valve (VIV) procedure is a safe alternative to conventional reoperation for bioprosthetic dysfunction. Balloon-expandable valve (BEV) and self-expanding valve (SEV) are the 2 major types of devices used. Evidence regarding the comparison of the 2 valves remains scarce. Methods A systematic review and meta-analysis was conducted to compare the outcomes of BEV and SEV in transcatheter VIV for aortic bioprostheses dysfunction. A computerized search of Medline, PubMed, Embase, and Cochrane databases was performed. English-language journal articles reporting SEV or BEV outcomes of at least 10 patients were included. Results In total, 27 studies were included, with 2,269 and 1,671 patients in the BEV and SEV groups, respectively. Rates of 30-day mortality and stroke did not differ significantly between the 2 groups. However, BEV was associated with significantly lower rates of postprocedural permanent pacemaker implantation (3.8% vs. 12%; P < 0.001). Regarding echocardiographic parameters, SEV was associated with larger postprocedural effective orifice area at 30 days (1.53 cm2 vs. 1.23 cm2; P < 0.001) and 1 year (1.55 cm2 vs. 1.22 cm2; P < 0.001). Conclusions For patients who underwent transcatheter aortic VIV, SEV was associated with larger postprocedural effective orifice area but higher rates of permanent pacemaker implantation. These findings provide valuable information for optimizing device selection for transcatheter aortic VIV.

Background Patients with chronic obstructive pulmonary disease (COPD) less often receive β-blockers after acute myocardial infarction (AMI). This may influence their outcomes after AMI. This study evaluated the efficacy of β-blockers after AMI in patients with COPD, compared with non-dihydropyridine calcium channel blockers (NDCCBs) and absence of these two kinds of treatment. Methods and results We conducted a nationwide population-based cohort study using data retrieved from Taiwan National Health Insurance Research Database. We collected 28,097 patients with COPD who were hospitalized for AMI between January 2004 and December 2013. After hospital discharge, 24,056 patients returned to outpatient clinics within 14 days (the exposure window). Those who received both β-blockers and NDCCBs (n = 302) were excluded, leaving 23,754 patients for analysis. Patients were classified into the β-blocker group (n = 10,638, 44.8%), the NDCCB group, (n = 1,747, 7.4%) and the control group (n = 11,369, 47.9%) based on their outpatient prescription within the exposure window. The β-blockers group of patients had lower overall mortality risks (adjusted hazard ratio [95% confidence interval]: 0.91 [0.83-0.99] versus the NDCCB group; 0.88 [0.84-0.93] versus the control group), but the risk of major adverse cardiac events within 1 year was not statistically different. β-blockers decreased risks of re-hospitalization for COPD and other respiratory diseases by 12-32%. Conclusions The use of β-blockers after AMI was associated with a reduced mortality risk in patients with COPD. β-blockers did not increase the risk of COPD exacerbations.

BackgroundPatients with cirrhosis and acute myocardial infarction (AMI) present dilemma whether dual antiplatelet therapy (DAPT) should be used.MethodsElectronic medical records between 2001-2013 were retrieved from Taiwan National Health Insurance Research Database. Patients were excluded for missing information, age ResultsA total of 150,887 patients with AMI retrieved. After exclusion criteria and propensity score-matching, 914 cirrhotic and 3,656 non-cirrhotic patients with AMI on DAPT were studied. During 1-year follow-up, there was significantly increased mortality in cirrhotic patients compared to non-cirrhotic patients (HR = 1.49, 95% CI = 1.28-1.74). There was significantly decreased recurrent MI in cirrhotic patients compared to non-cirrhotic patients (subdistribution HR [SHR] = 0.71, 95% CI = 0.54-0.92). However, non-significantly increased major bleeding (SHR = 1.23, 95% CI = 0.87-1.73) and significantly increased gastrointestinal bleeding (SHR = 1.49, 95% CI = 1.31-1.70).ConclusionsIn cirrhotic patients with AMI, DAPT offers benefit with decreased recurrent MI at the expense of increased gastrointestinal bleeding.

ObjectivesThe purpose of this study was to examine the impact of epidermal growth factor receptor (EGFR) mutation status and tyrosine kinase inhibitors (TKIs) on the survival of brain metastases (BM) in patients with surgically resected non-small cell lung cancer (NSCLC).MethodsWe selected the patients who had developed metastatic NSCLC; analyzed the differences between brain metastases and other sites of metastases, including patient characteristics, EGFR status, and survival; and selected the patients who had BM for further investigation. We also compared the treatment effects of first-generation TKIs with those of second-/third-generation TKIs.ResultsA total of 785 cases of stage I-IIIa NSCLC were reviewed. Thirty-six (4.6%) patients were identified as having BM. Among them, 14 patients had a mutated EGFR status. No association between EGFR mutation and the incidence of BM was observed (p = 0.199). Patients with mutated EGFRs had significantly longer overall survival and post-recurrence survival than patients with wild-type EGFR mutation (p = 0.001 for both). However, there was no survival difference between patients with exon 19 and exon 21 mutations (p = 0.426). Furthermore, patients who received the second- and/or third-generation EGFR-TKIs had better survival than patients who only received first-generation EGFR-TKIs (p = 0.031). A multivariate analysis indicated that the next-generation TKIs (HR, 0.007; 95% CI, 0.000 to 0.556; p = 0.026) and a longer interval before BM development (HR, 0.848; 95% CI, 0.733 to 0.980; p = 0.025) were significant factors in longer survival.ConclusionsEGFR-TKIs were effective in treating NSCLC patients with BM after curative pulmonary surgery, especially in those patients harboring EGFR mutations. Furthermore, the second-/third-generation EGFR-TKIs showed more promising results than the first-generation EGFR-TKIs in treating those particular patients, though larger studies needed to further prove the results.

Osteoarthritis (OA), one of the most common joint disease, affects more than 80% of the population aged 70 or over. Mesenchymal stem cells (MSCs) show multi-potent differentiation and self-renewal capability, and, after exposure to an inflammatory environment, also exhibit immunosuppressive properties. In this study, we have used a model of lipopolysaccharide (LPS)-stimulated chondrocytes to evaluate MSC anti-inflammatory efficacy. The anti-inflammatory mechanism was tested in two cell-contained culture systems: (i) MSC-chondrocyte indirect contact system and (ii) MSC-chondrocyte direct contact system, and one cytokine-only culture system: MSC-conditioned medium (CM) system. Results showed that MSCs reduced chondrocyte inflammation through both paracrine secretion and cell-to-cell contact. The inflammation-associated, and free-radical-related genes were down-regulated significantly in the direct contact system on 24 h, however, the TNF-α. IL-6 were upregulated and aggrecan, COLII were downregulated on 72 h in direct contact system. Moreover, we found CM produced by MSC possess well therapeutic effect on inflammatory chondorcyte, and the 10-fold concentrated MSC-conditioned medium could down-regulated chondorcyte synthesis inflammation-associated, and free-radical-related genes, such as TNF-α, IL-1β, IL-6 and iNOS even treated for 72 h. In conclusion, MSC-CM showed great potential for MSC-based therapy for OA.

Unilateral sinus disease (USD) can sometimes be difficult to accurately diagnose before surgery. The application of nasal nitric oxide (nNO) for USD diagnosis and its surgical outcome in USD has not been reported in the literature. We prospectively enrolled sixty-six USD patients who underwent endoscopic sinus surgery for fungal rhinosinusitis (n = 19), chronic rhinosinusitis (CRS) without nasal polyps (n = 13), CRS with nasal polyps (n = 12) and sinonasal mass lesions (n = 22). nNO levels were measured preoperatively and at three and six months postoperatively. Correlations between nNO levels and potential clinical parameters, type of disease, disease severity, and disease-related quality of life (QOL) were assessed. Unlike bilateral CRS, in USD, nNO levels did not correlate with disease severity or postoperative QOL improvements. Except for fungus group, there were no differences in nNO levels between lesion and non-lesion sides in all the other groups. nNO levels on both sides were significantly elevated six months postoperatively in all groups. Fungal rhinosinusitis patients had the lowest preoperative nNO levels, and a cutoff of 239.3 ppb had the best sensitivity (79.0%) and specificity (87.2%) for preoperative diagnosis. While preoperative nNO levels cannot serve as an alternative marker for disease severity of USD, they were lower in fungal rhinosinusitis patients than in other USD patients and may be useful for more accurate diagnosis prior to surgery.

ObjectiveThis study aims to investigate the association of serum vitamin D (VD) levels with the severity of liver fibrosis (LF) in post Kasai's portoenterostomy biliary atresia (PKBA) patients living with their native liver.MethodsIn this cross-sectional study, carried out in a tertiary Children's Hospital in Taipei, Taiwan, PKBA patients living with their native liver were enrolled. Liver biochemistry data, serum 25-hydroxyvitamin D (25-OHVD), acoustic radiation force impulse (ARFI), and scores of Pediatric Quality of Life questionnaire (PedsQL) were collected.ResultsAll the enrolled 33 PKBA patients (36.4% males), aged 1-23 years, possessed 25-OHVD less than 30ng/ml. An inverse correlation was detected between serum 25-OHVD and ARFI (r2 = 0.175; p = 0.024). We selected a cutoff value of 23ng/mL to divide PKBA patients into two groups, as the p-value was the most significant at this point when comparing the median ARFI of two groups (p = 0.003). Ten (30.3%) had 25-OHVD≥23ng/ml (HVD group), whereas 23(69.7%) had 25-OHVDConclusionVD levels are inversely associated with severity of LF in PKBA patients with native liver.

Coexistence of chronic rhinosinusitis (CRS) with asthma appears to impair asthma control. Type-2 innate lymphoid cells (ILC2s) respond to the cytokines of thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33, thus contributing to airway diseases such as CRS and asthma. We investigate whether the augmented Th2-cytokines in CRS might be related to sinonasal tract ILC2s corresponding to enhanced IL-25, IL-33 and TSLP release in severe asthmatics, and be involved in asthma control. Twenty-eight asthmatics (12 non-severe and 16 severe) with CRS receiving nasal surgery were enrolled. The predicted FEV1 inversely associated with CRS severity of CT or endoscopy scores. Higher expression of Th2-driven cytokines (IL-4, IL-5, IL-9, and IL-13), TSLP, IL-25 and IL-33 in nasal tissues was observed in severe asthma. Severe asthmatics had higher ILC2 cell counts in their nasal tissues. ILC2 counts were positively correlated with Th2-cytokines. Nasal surgery significantly improved asthma control and lung function decline in severe asthma and CRS. The higher expression of IL-33/ILC2 axis-directed type 2 immune responses in nasal tissue of CRS brought the greater decline of lung function in severe asthma. ILC2-induced the upregulated activity of Th2-related cytokines in asthmatics with CRS may contribute to a recalcitrant status of asthma control.

[This corrects the article DOI: 10.1371/journal.pone.0062817.].

Background Studies have shown a higher risk of depressive disorders in children with sleep apnea than in those without sleep apnea. However, the association between sleep apnea and subsequent depressive disorders in the pediatric population remains undetermined. Thus, this study investigated the risk of depressive disorders among pediatric patients with sleep apnea. Methods In this study, the population-based National Health Insurance Research Database of Taiwan was used to identify patients who had first been diagnosed with sleep apnea between 1999 and 2013. Patients with sleep apnea who were younger than 18 years were included in the sleep apnea group. Controls (those without sleep apnea) were matched to patients with sleep apnea at a 1:10 ratio by age, sex, and index year. Patients who had baseline or inherited depressive disorders before the enrollment date were excluded. The two groups were followed up until December 31, 2013. The primary endpoint was the occurrence of one or more depressive disorders. Results At the end of this study, 6,237 children had been enrolled, comprising 567 children with sleep apnea and 5,670 children without sleep apnea. During the mean follow-up period of 5.87 years, a total of 77 children (1.23%) developed one or more depressive disorders; 14 (2.46%) from the sleep apnea group and 63 (1.11%) from the control group. Kaplan–Meier analysis showed that children with sleep apnea had a significantly higher risk of depressive disorders (log-rank test, p = 0.002). After adjusting for covariates, the risk of subsequent depressive disorders among children with sleep apnea was still significantly higher (hazard ratio [HR] = 2.25; 95% confidence interval [CI] = 1.25–4.05; p = 0.006). Moreover, boys with sleep apnea had a significantly higher risk than those without sleep apnea (adjusted HR = 3.77; 95% CI, 1.82–7.54; p < 0.001). Furthermore, in sleep apnea group, children older than 12 years of age had more risk to depression (hazard ratio (HR) = 7.1833, 95% confidence interval (CI), 2.3734 to 21.7411; p = 0.0004). Conclusions This study found a significantly higher subsequent risk of depressive disorders in children with sleep apnea, particularly boys and those older than 12 years of age. The study findings strongly suggest that clinicians should provide psychological evaluation and supportive care for children with sleep apnea, in addition to medical treatment.

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry.

Background Studies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results. Objective To determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis. Methods For the case-control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta-analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk. Results We found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76–1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95–1.99)] and a high heterogeneity (I2: 87.2%). Conclusions The association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted.

Background It is unclear whether oral anticoagulants are beneficial for atrial fibrillation (AF) patients with low CHA2DS2-VASc score. Age could be important in determining the risk of thromboembolism in low risk AF patients (CHA2DS2-VASc score of 1 for male or 2 for female). Methods The Taiwan National Health Insurance Research Database (NHIRD) was used and 27,521 AF patients with CHA2DS2-VASc score of 1 (male) or 2 (female) not receiving anticoagulants were acquired as the study cohort, which were classified into three age groups: 20–49, 50–64, and 65–74 years. The clinical endpoint was the occurrence of ischemic thromboembolism within one year of follow up. Results During the follow-up of 0.94 ± 0.19 years, 385 (2.19%) male patients experienced ischemic thromboembolism, with annual rate of 2.32%. The annual risk ranged from 1.29%, 2.43% to 2.77% for male patients aged 20–49, 50–64 and 65–74 years respectively. Of the female patients, 218 (2.20%) experienced clinical event with annual rate of 2.32%. The annual risk increased from 1.87%, 2.28% to 2.64% for female patients aged 20–49, 50–64 and 65–74 years respectively. There was no difference in risk between the male patients aged 20–49 years with CHA2DS2-VASc score of 1 and overall male patients with CHA2DS2-VASc score of 0. (P = 0.631) The female patients aged 20–49 years with CHA2DS2-VASc score of 2 was associated with a higher risk of thromboembolic events than overall female patients with CHA2DS2-VASc score of 1 (HR = 1.93; P = 0.008). Conclusions Age is important in determining the risk of thromboembolism in AF patients with single risk factor. In male patients

Objective To investigate the efficacy and long-term clinical benefits of DES for dialysis patients. Background It is unclear whether percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is associated with lower rates of major adverse cardiovascular events (MACE) or mortality compared to bare-metal stents (BMS). Methods From a nationwide cohort selected from Taiwan’s National Health Insurance Research Database, we enrolled 2,835 dialysis patients who were hospitalized for PCI treatment with stent implantation from Dec 1, 2006. Follow-up was from the date of index hospitalization for PCI until the first MACE, date of death, or December 31, 2011, whichever came first. Results A total of 738 patients (26.0%) had DES implanted, and 2,097 (74%) had BMS implanted. The medium time to the first MACE was 0.53 years (interquartile range: 0.89 years; range: 0–4.62 years). At 1-year follow-up, patients treated with BMS had significantly, non-fatal myocardial infarction (MI), all-cause mortality, and composite MACE compared to those treated with DES. The overall repeat revascularization with coronary artery bypass graft (CABG), non-fatal MI, all-cause mortality, and composite MACE were significantly lower in patients treated with DES than those treated with BMS. Multivariate cox regression analysis showed that older age, history of diabetes, history of heart failure, history of stroke, and DES vs. BMS were independent significant predictors of MACE. Conclusions DES implantation conferred survival benefits in dialysis patients compared with BMS implantation.

Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.

Background & Aims To evaluate the risk of depressive disorders among patients with Hepatocellular Carcinoma (HCC) using the National Health Insurance Research Database (NHIRD) in Taiwan. Methods We conducted a retrospective study of a newly diagnosed HCC cohort of 55,973 participants who were selected from the NHIRD. Patients were observed for a maximum of 6 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in HCC patients. Results Of the total 55,973 HCC patients, 1,041 patients (1.86%) were diagnosed with depressive disorders during a mean (SD) follow-up period of 1.1 (1.2) years. The Cox multivariate proportional hazards analysis showed that age of 40–59 (HR 1.376, 95% CI 1.049–1.805, p = 0.021), age of 60–79 (HR 1.341, 95% CI 1.025–1.753, p = 0.032), women (HR 1.474 95% CI 1.301–1.669, p < 0.001), metastasis (HR 1.916, 95% CI 1.243–2.953, p = 0.003), and HCV (HR 1.445, 95% CI 1.231–1.697, p < 0.001) were independent risk factors for developing depressive disorders. Conclusions Our study indicated a subsequent risk of depressive disorders in patients with HCC, and the risk increased for those with female gender, aged 40 to 59, aged 60 to 79, with metastasis, or with HCV. Psychological evaluation and support are two critical issues in these HCC patients with the risk factors.

The purpose of this study was to measure the long-term growth of the mandible in miniature pigs using 3D Cone-Beam Computerized Tomography (CBCT). The mandibles of the pigs were scanned monthly over 12 months using CBCT and the 3D mandibular models were reconstructed from the data. Seventeen anatomical landmarks were identified and classified into four groups of line segments, namely anteroposterior, superoinferior, mediolateral and anteroinferior. The inter-marker distances, inter-segmental angles, volume, monthly distance changes and percentage of changes were calculated to describe mandibular growth. The total changes of inter-marker distances were normalized to the initial values. All inter-marker distances increased over time, with the greatest mean normalized total changes in the superoinferior and anteroposterior groups (p0.05). Monthly distance changes were greatest during the first four months and then reduced over time. Percentages of inter-marker distance changes were similar among the groups, reaching half of the overall growth around the 4th month. The mandibular volume growth increased non-linearly with time, accelerating during the first five months and slowing during the remaining months. The growth of the mandible was found to be anisotropic and non-homogeneous within the bone and non-linear over time, with faster growth in the ramus than in the body. These growth patterns appeared to be related to the development of the dentition, providing necessary space for the teeth to grow upward for occlusion and for the posterior teeth to erupt.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3-6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents.

BackgroundBreast cancer survivors have an increased risk of bone fracture. But the risk among young patients with adjuvant therapies remains unknown. This population-based study is aimed to assess the incidence and risk of fracture among young (age of 20 to 39 years) breast cancer patients who received adjuvant therapies.MethodsFrom January 2001 to December 2007, 5,146 newly diagnosed breast cancer patients were enrolled from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients were observed for a maximum of 6 years to determine the incidence of newly onset fracture. Kaplan Meier and Cox regression analyses were used to evaluate the risk of fracture in young breast cancer patients who received adjuvant treatments.ResultsOf the total 5,146 young (age of 20 to 39 years) breast cancer patients, the Cox multivariate proportional hazards analysis showed that AIs, radiotherapy, and monoclonal antibodies were significantly associated with a high risk of fracture. Moreover, patients who received AIs for more than 180 days had a high hazard ratio (HR) of 1.77 (95% CI = 0.68-4.57), and patients who received more than four radiotherapy visits had a high HR of 2.54 (95% CI = 1.07-6.06). Under the site-specific analysis, young breast cancer patients who received AIs had the highest risk of hip fracture (HR = 8.520, 95% CI = 1.711-42.432, p < 0.04), whereas patients who received radiotherapy had the highest risk of vertebral fracture (HR = 5.512, 95% CI = 1.847-16.451, p < 0.01).ConclusionYoung breast cancer patients who are receiving AIs, radiotherapy or monoclonal antibody need to be more careful for preventing fracture events. Breast cancer treatment plans are suggested to incorporate fracture prevention interventions.

Abdominal aortic aneurysm (AAA) is a life-threatening situation affecting almost 10% of elders. There has been no effective medication for AAA other than surgical intervention. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to have a protective effect on cardiovascular disease. Whether DPP-4 inhibitors may be beneficial in the treatment of AAA is unclear. We investigated the effects of DPP-4 inhibitor sitagliptin on the angiotensin II (Ang II)-infused AAA formation in apoE-deficient (apoE-/-) mice. Mice with induced AAA were treated with placebo or 2.5, 5 or 10 mg/kg/day sitagliptin. Ang II-infused apoE-/- mice exhibited a 55.6% incidence of AAA formation, but treatment with sitagliptin decreased AAA formation. Specifically, administered sitagliptin in Ang II-infused mice exhibited decreased expansion of the suprarenal aorta, reduced elastin lamina degradation of the aorta, and diminished vascular inflammation by macrophage infiltration. Treatment with sitagliptin decreased gelatinolytic activity and apoptotic cells in aorta tissues. Sitaglipitn, additionally, was associated with increased levels of plasma active glucagon-like peptide-1 (GLP-1). In vitro studies, GLP-1 decreased reactive oxygen species (ROS) production, cell migration, and MMP-2 as well as MMP-9 activity in Ang II-stimulated monocytic cells. The results conclude that oral administration of sitagliptin can prevent abdominal aortic aneurysm formation in Ang II-infused apoE-/-mice, at least in part, by increasing of GLP-1 activity, decreasing MMP-2 and MMP-9 production from macrophage infiltration. The results indicate that sitagliptin may have therapeutic potential in preventing the development of AAA.

Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model.Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orally administrated daily saline, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi). Diarrhea score, pro-inflammatory cytokines serum levels, intestinal villus height and crypt depth and total RNA from tissue were assessed. Samples of blood, liver and spleen tissues were assessed for translocation.Marked diarrhea developed in the 5-FU groups but was attenuated after oral Lcr35 and LaBi administrations. Diarrhea scores decreased significantly from 2.64 to 1.45 and 0.80, respectively (P0.001). Those mice in 5-FU groups had significantly higher proinflammatory cytokine levels (TNF-α: 234.80 vs. 29.10, P0.001, IL-6: 25.13 vs. 7.43, P0.001, IFN-γ: 22.07 vs. 17.06, P = 0.137). A repairing of damage in jejunal villi was observed following probiotics administration. We also found TNF-α, IL-1β and IL-6 mRNA expressions were up-regulated in intestinal mucositis tissues following 5-FU treatment (TNF-α: 4.35 vs. 1.18, IL-1β: 2.29 vs. 1.07, IL-6: 1.49 vs. 1.02) and that probiotics treatment suppressed this up-regulation (P0.05). No bacterial translocation was found in this study.In conclusion, our results show that oral administration of probiotics Lcr35 and LaBi can ameliorate chemotherapy-induced intestinal mucositis in a mouse model. This suggests probiotics may serve as an alternative therapeutic strategy for the prevention or management of chemotherapy-induced mucositis in the future.

This study aimed to investigate the association between herpes zoster (HZ) and human immunodeficiency virus (HIV). Data were retrieved from the Longitudinal Health Insurance Databases (LHID 2005 and 2010), Taiwan. The International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes were used to identify Hz from 2001-2004. Identification of HIV infection was from 2005-2010. The hazard ratios of HIV among herpes zoster infected and non-herpes zoster infected patients were estimated using multiple Cox proportional hazard model. In general, 19685 participants were identified with Hz. The HIV incidence rates (per 104 person-months) in herpes zoster infected and non-infected patients were 0.191(95% CI 0.130-0.280) and 0.079 (95% CI 0.074-0.084), respectively while the hazard ratio (HR) of HIV among infected individuals was 3.518 (95% CI 2.375-5.211). This study concludes that herpes zoster could be considered as a predictor of HIV infection especially among Asian populations, hence it is vital to test herpes zoster infected individuals for HIV antibodies.

Salmonella, a common zoonotic pathogen, causes gastroenteritis in both humans and animals. Traditional Chinese Medicine (TCM) has been used to improve gastrointestinal dysfunction and to modify the immune response to inflammation for centuries. This study used six herbal plants and four TCM formulae to rate their efficacy in preventing S. Typhimurium infection via mouse model. Minimum bactericidal concentration (MBC) of Coptidis rhizome (CR) against the reference strain tallied 12.5 mg/ml and against clinical isolate ST21 was 25 mg/ml. MBCs of other herbal extracts and formulae on Salmonella Typhimurium strains were above 50 mg/ml. In the mice model, CR and Si Jun Zi Tang (SJZT) could significantly decrease the bacterial load in organs and blood after being challenged, along with body weight loss due to the infection. CR and SJZT alleviated infection-induced interferon-gamma levels in the serum and tissues, and tumor necrosis factor-alpha (TNF-α) levels in intestinal tissues. CR and SJZT serum metabolites could suppress S. Typhimurium invasion and TNF-α expression in RAW264.7 cells. The therapeutic activity of CR and SJZT may involve berberine, ginsenoside Rb1, and glycyrrhizin, interfering with Salmonella when invading macrophages. CR and SJZT has shown potential in preventing S. Typhimurium infection through the regulation of the immune response.

The purpose of this study was to measure the long-term growth of the mandible in miniature pigs using 3D Cone-Beam Computerized Tomography (CBCT). The mandibles of the pigs were scanned monthly over 12 months using CBCT and the 3D mandibular models were reconstructed from the data. Seventeen anatomical landmarks were identified and classified into four groups of line segments, namely anteroposterior, superoinferior, mediolateral and anteroinferior. The inter-marker distances, inter-segmental angles, volume, monthly distance changes and percentage of changes were calculated to describe mandibular growth. The total changes of inter-marker distances were normalized to the initial values. All inter-marker distances increased over time, with the greatest mean normalized total changes in the superoinferior and anteroposterior groups (p

BackgroundData from a large patient population regarding very long-term outcomes after BMS implantation are inadequate. This study aimed to evaluate the very long-term (8-17 years) clinical and long-term (3-5 years) angiographic outcomes after intracoronary bare-metal stenting (BMS).Methods and resultsFrom the Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions (CAPTAIN) registry, a total of 2391 patients with 2966 lesions treated with 3190 BMSs between November 1995 and May 2004 were evaluated. In total, 1898 patients with 2364 lesions, and 699 patients with 861 lesions underwent 6-month and 3- to 5- year angiographic follow-up, respectively. During a mean follow-up period of 149 ± 51 months, 18.6% of the patients died (including 10.8% due to cardiac death), 6.1% developed reinfarction, 16.2% had target lesion revascularization (including 81% of the patients within the first year), 14.5% underwent new lesion stenting (including 72% of the patients after 3 years), 2.4% underwent coronary bypass surgery, and 1.6% had definite stent thrombosis. The overall cardiovascular event-free survival rate was 58.5%. The 6-month angiographic study indicated a 20% restenosis rate. The minimal luminal diameter increased from 0.65 ± 0.44 mm to 3.02 ± 0.46 mm immediately after stenting, decreased to 2.06 ± 0.77 mm at the 6-month follow-up, and increased to 2.27 ± 0.68 mm at the 3- to 5-year follow-up.ConclusionsThis study provides clinical and angiographic results from a large population of patients who underwent BMS implantations after a long-term follow-up period (149 ± 51 months). The progression of coronary atherosclerosis developed over time, and presented with new lesion required stent implantation. The follow-up angiographic findings reconfirmed the late and sustained improvement in luminal diameter between 6 months and 3-5 years.

Background Diadenosine tetraphosphate (Ap4A), a constituent of platelet dense granules, and its P1,P4-dithio and/or P2,P3-chloromethylene analogs, inhibit adenosine diphosphate (ADP)-induced platelet aggregation. We recently reported that these compounds antagonize both platelet ADP receptors, P2Y1 and P2Y12. The most active of those analogs, diadenosine 5′,5″″-P1,P4-dithio-P2,P3-chloromethylenetetraphosphate, (compound 1), exists as a mixture of 4 stereoisomers. Objective To separate the stereoisomers of compound 1 and determine their effects on platelet aggregation, platelet P2Y1 and P2Y12 receptor antagonism, and their metabolism in human plasma. Methods We separated the 4 diastereomers of compound 1 by preparative reversed-phase chromatography, and studied their effect on ADP-induced platelet aggregation, P2Y1-mediated changes in cytosolic Ca2+, P2Y12-mediated changes in VASP phosphorylation, and metabolism in human plasma. Results The inhibition of ADP-induced human platelet aggregation and human platelet P2Y12 receptor, and stability in human plasma strongly depended on the stereo-configuration of the chiral P1- and P4-phosphorothioate groups, the SPSP diastereomer being the most potent inhibitor and completely resistant to degradation in plasma, and the RPRP diastereomer being the least potent inhibitor and with the lowest plasma stability. The inhibitory activity of SPRP diastereomers depended on the configuration of the pseudo-asymmetric carbon of the P2,P3-chloromethylene group, one of the configurations being significantly more active than the other. Their plasma stability did not differ significantly, being intermediate to that of the SPSP and the RPRP diastereomers. Conclusions The presently-described stereoisomers have utility for structural, mechanistic, and drug development studies of dual antagonists of platelet P2Y1 and P2Y12 receptors.

Cerebral vasoreactivity (CVR) can be assessed by functional MRI (fMRI) using hypercapnia challenges. In normal subjects, studies have shown temporal variability of CVR blood oxygenation level-dependent responses among different brain regions. In the current study, we analyzed the variability of BOLD CVR dynamics by fMRI with a breath-holding task in 17 subjects with unilateral carotid stenosis before they received carotid stenting. Great heterogeneity of CVR dynamics was observed when comparing BOLD responses between ipsilateral and contralateral hemispheres in each patient, especially in middle cerebral artery (MCA) territories. While some subjects (n=12) had similar CVR responses between either hemisphere, the others (n=5) had a poorly correlated pattern of BOLD changes between ipsilateral and contralateral hemispheres. In the latter group, defined as impaired CVR, post-stenting perfusion tended to be more significantly increased. Our data provides the first observation of divergent temporal BOLD responses during breath holding in patients with carotid stenosis. The development of collateral circulation and the derangement of cerebral hemodynamics can be detected through this novel analysis of the different patterns of BOLD changes. The results also help in prediction of robust increase of perfusion or hyperperfusion after carotid stenting.

Multipartite viruses contain more than one distinctive genome component, and the origin of multipartite viruses has been suggested to evolve from a non-segmented wild-type virus. To explore whether recombination also plays a role in the evolution of the genomes of multipartite viruses, we developed a systematic approach that employs motif-finding tools to detect conserved motifs from divergent genomic regions and applies statistical approaches to select high-confidence motifs. The information that this approach provides helps us understand the evolution of viruses. In this study, we compared our motif-based strategy with current alignment-based recombination-detecting methods and applied our methods to the analysis of multipartite single-stranded plant DNA viruses, including bipartite begomoviruses, Banana bunchy top virus (BBTV) (consisting of 6 genome components) and Faba bean necrotic yellows virus (FBNYV) (consisting of 8 genome components). Our analysis revealed that recombination occurred between genome components in some begomoviruses, BBTV and FBNYV. Our data also show that several unusual recombination events have contributed to the evolution of BBTV genome components. We believe that similar approaches can be applied to resolve the evolutionary history of other viruses.

Background Long lesions have been associated with adverse outcomes in percutaneous coronary interventions with bare metal stents (BMS). However, the exact impact of lesion length on the short- and long-term outcomes of drug-eluting stent (DES) implantations is not as clear. Methods and Results This study compared the impact of lesion length on angiographic and clinical outcomes of BMS and DES in a single-center prospective registry. Lesion length was divided into tertiles. The primary endpoints were angiographically defined binary in-stent restenosis (ISR) rate and major adverse cardiac event (MACE). Of the 4,312 de novo lesions in 3,447 consecutive patients in the CAPTAIN registry, 2,791 lesions (of 2,246 patients) received BMS, and the remaining 1,521 lesions (of 1,201 patients) received DES. The mean follow-up duration was 4.5 years. The longer the lesion, the higher the ISR rate (14%, 18%, and 29%, p

OBJECTIVES: Recurrent falls not only have risk factors different from those of single falls but also have less favorable outcomes. The aim of our study was to determine the association between the injury characteristics of a first fall and the likelihood of recurrent injurious falls in a cohort of hospitalized patients. METHODS: We designed a nationwide retrospective cohort study and selected hospitalized patients who had injurious falls between 2001 and 2010. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of recurrent injurious falls requiring hospitalization in the following year on the basis of the patients' demographic characteristics, comorbidities, and the characteristics of injuries from the first injurious fall requiring hospitalization. RESULTS: Among the 504 512 patients hospitalized for injurious falls, 19 442 experienced recurrent injurious falls requiring hospitalization. The 1-year incidence of recurrent injurious falls requiring hospitalization was 3.85%. The incidence density was the highest within the 3-month period after the first injurious fall. The risk of recurrent injurious falls among patients aged 40 to 64, 65 to 74, and ≥ 75 years increased progressively (HR: 2.11, 95% confidence interval [CI]: 1.90-2.34; HR: 2.80, 95% CI: 2.51-3.11; and HR: 3.80, 95% CI: 3.42-4.23, respectively). The length of hospitalization (LOH) ≥ 15 or ≥ 31 days (HR: 1.39, 95% CI: 1.30-1.48; and HR: 1.59, 95% CI: 1.43-1.77, respectively) and injury to the head (HR: 1.59, 95% CI: 1.53-1.65) or spine (HR: 1.66, 95% CI: 1.59-1.74) were also found to be major risk factors. CONCLUSIONS: Our findings show that the LOH and head and spine injuries are associated with an increased risk of recurrent injurious falls leading to hospitalization. The risk of recurrent injurious falls requiring hospitalization increased significantly among adults older than 40 years. We suggest further research on the effects of injury characteristics associated with the first injurious fall requiring hospitalization and resultant anatomical damages on the risk of recurrent injurious falls requiring hospitalization. High-risk patients should receive tailored rehabilitation addressing their respective injuries within 3 months after hospital discharge. Language: en

The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

Background Clopidogrel is a prodrug that undergoes in vivo bioactivation to show its antiplatelet effects. Recent studies have shown that cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogrel bioactivation. Here, we aim to determine the effects of genetic polymorphisms of CYP (CYP 2C19*2, CYP 2C19*3, and CYP 2C19*17), ABCB1 (ABCB1 3435C>T, ABCB1 129T>C, and ABCB1 2677G>T/A), and PON1 (PON1 Q192R, PON1 L55M, and PON1 108C>T) on the development of stent thrombosis (ST) in patients receiving clopidogrel after percutaneous coronary intervention (PCI). Methods and Results We evaluated the incidence of ST (0.64%) in 4964 patients who were recruited in the CAPTAIN registry (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions). The presence of genetic polymorphisms was assessed in 20 subjects who developed ST after aspirin and clopidogrel therapy and in 40 age- and sex-matched control subjects who did not develop ST, which was documented after 9 months of angiographic follow-up. ST was acute in 5 subjects, subacute in 7, late in 7, and very late in 1. The presence of CYP 2C19*2 allele was significantly associated with ST (adjusted odds ratio [ORadj]: 4.20, 95% confidence interval [CI], 1.263–9.544; P = 0.031). However, genetic variations in PON1 and ABCB1 showed no significant association with ST. Conclusion We conclude that in a Taiwanese population, PON1 Q192R genotype is not associated with ST development after PCI. However, the presence of CYP 2C19*2 allele is a risk factor for ST development after PCI.

Human respiratory syncytial virus (RSV) constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although "controlled" inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1β (IL-1β) plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1β is synthesized as an immature pro-IL-1β form. It is cleaved by activated caspase-1 to yield mature IL-1β that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1β release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1β secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1β production during RSV infection. Further studies illustrated that prior to inflammasome formation; the "first signal" constitutes activation of toll-like receptor-2 (TLR2)/MyD88/NF-κB pathway. TLR2/MyD88/NF-κB signaling is required for pro-IL-1β and NLRP3 gene expression during RSV infection. Following expression of these genes, two "second signals" are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS) and potassium (K(+)) efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-κB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1β release during RSV infection.

Background The moth orchid (Phalaenopsis species) is an ornamental crop that is highly commercialized worldwide. Over 30,000 cultivars of moth orchids have been registered at the Royal Horticultural Society (RHS). These cultivars were obtained by artificial pollination of interspecific hybridization. Therefore, the identification of different cultivars is highly important in the worldwide market. Methods/Results We used Illumina sequencing technology to analyze an important species for breeding, Phalaenopsis aphrodite subsp. formosana and develop the expressed sequence tag (EST)-simple sequence repeat (SSR) markers. After de novo assembly, the obtained sequence covered 29.1 Mb, approximately 2.2% of the P. aphrodite subsp. formosana genome (1,300 Mb), and a total of 1,439 EST-SSR loci were detected. SSR occurs in the exon region, including the 5’ untranslated region (UTR), coding region (CDS), and 3’UTR, on average every 20.22 kb. The di- and tri-nucleotide motifs (51.49% and 35.23%, respectively) were the two most frequent motifs in the P. aphrodite subsp. formosana. To validate the developed EST-SSR loci and to evaluate the transferability to the genus Phalaenopsis, thirty tri-nucleotide motifs of the EST-SSR loci were randomly selected to design EST-SSR primers and to evaluate the polymorphism and transferability across 22 native Phalaenopsis species that are usually used as parents for moth orchid breeding. Of the 30 EST-SSR loci, ten polymorphic and transferable SSR loci across the 22 native taxa can be obtained. The validated EST-SSR markers were further proven to discriminate 12 closely related Phalaenopsis cultivars. The results show that it is not difficult to obtain universal SSR markers by transcriptome deep sequencing in Phalaenopsis species. Conclusions This study supported that transcriptome analysis based on deep sequencing is a powerful tool to develop SSR loci in non-model species. A large number of EST-SSR loci can be isolated, and about 33.33% EST-SSR loci are universal markers across the Phalaenopsis breeding germplasm after preliminary validation. The potential universal EST-SSR markers are highly valuable for identifying all of Phalaenopsis cultivars.