Search

Background: Individuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan Methods: Between 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 μm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. Results: Of 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 μg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. Conclusions: This longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

Background: The coronavirus disease 2019 (COVID-19) pandemic not only profoundly changed people’s living and consumption habits but also affected their physical and mental health and life satisfaction. Healthcare workers reportedly have higher anxiety levels than the general population, and their response to major difficult events, including life, work, and natural and man-made disasters, is affected by their resilience level. Objectives: This study aimed to understand the correlation between healthcare workers’ self-perceived health, psychological resilience, and life satisfaction and to further analyze the mediating effect of psychological resilience between self-perceived health and life satisfaction. Methods: This study adopted a cross-sectional, purpose-sampling survey design to recruit, and select participants aged over 20 years at a regional, teaching hospital in Central Taiwan. The questionnaire included basic data, self-perceived health, psychological resilience, and life satisfaction. This study collected answered questionnaires from 399 (88.7%) respondents. The mediating effect of psychological resilience on the relationship between self-perceived health and life satisfaction was examined using Pearson’s product-moment correlation coefficient analysis and bootstrapping. Results: The mean age was 34.51 ± 9.88 years. Self-perceived health, psychological resilience, and life satisfaction were at good levels. Significant differences were noted in sex, position, and education in terms of psychological resilience and life satisfaction. Psychological resilience partially mediated self-perceived health and life satisfaction. Conclusion: Psychological resilience has a partial mediating effect on healthcare workers’ life satisfaction, indicating an important driving factor for life satisfaction. Furthermore, the psychological process of employees’ resilience can be explained by self‑perceived health.

We explored the use of biomimetic structures, including those that mimic leaf structures, to enhance the angular color uniformity of flat phosphor-converted light-emitting diodes (pcLEDs). The distinct microstructures found on natural leaf surfaces, such as micro-scale bumps, ridges, and hierarchical patterns, have inspired the design of artificial microstructures that can improve light extraction, scattering, and overall optical performance in LED applications. The effects of these leaf surface microstructures on the phosphor layer of flat pcLEDs were evaluated. An imprinting technique was employed to directly replicate the surface morphology structures from fresh plant leaves. The results indicated that this method provided excellent scattering capability and reduced the disparity in light output between blue and yellow light emissions from flat pcLEDs at various angles. Subsequently, uniform correlated color temperature in the flat pcLEDs was achieved, reducing the yellow ring effect. Furthermore, the availability of diverse wrinkle and surface patterns from a wide range of natural prototypes could reduce design costs compared with traditional mold fabrication, making the method suitable for application in mass production.

Purpose: This study investigated the oncological and functional surgical outcomes for patients with renal tumor who underwent robot-assisted partial nephrectomy (PN) by a single surgeon in Taiwan from 2006 to 2019. Methods: This retrospective study assessed patients who underwent robot-assisted PN for renal tumor. Patient data were analyzed for age, sex, body mass index, operative time and total ischemic time, surgical margin (positive/negative), and surgical complications. To evaluate functional and oncological outcomes, achievement of trifecta, and pentafecta criteria was used. Trifecta criteria were defined as a negative surgical margin, no postoperative complications, warm ischemia time 90% preservation of estimated glomerular filtration rate (eGFR) preservation, and no stage progression of chronic kidney disease at 1-year follow-up. Results: Of 101 patients who received robot-assisted PN, the most common type of renal tumor was clear cell renal cell carcinoma (RCC) (38%), followed by angiomyolipoma (26%). Patient characteristics were mean age 54.59 ± 13.8 years; mean RENAL Nephrometry score 6.63 ± 2.16; mean operative time 102.34 ± 50.06 min; and warm ischemia time 20.01 ± 14.12 min. The mean eGFR was 104.43 ± 31.73 mL/min/1.73 m2 preoperatively and 89.39 ± 32.3 mL/min/1.73 m2 postoperatively. Pathologic evaluation showed malignant tumors in 57 patients, among whom achievement of trifecta criteria occurred for 39 (68.42%) and pentafecta criteria for 18 (31.57%). Operation time was the only predictor for pentafecta achievement. Conclusion: Robotic PN is a safe and effective approach for patients with renal tumor that can preserve most renal function and achieve oncological control. Pentafecta criteria can be used to more clearly define the surgical outcome of RAPN.

The clinical characteristics and long-term outcomes of patients with ischemic stroke (IS) and atrial fibrillation detected after stroke (AFDAS) have not been clearly established. Previous studies evaluating patients with AFDAS were limited by the low prescription rates of anticoagulants and short follow-up periods. Consecutive patients hospitalized for IS between 2014 and 2017 were identified from a National Health Insurance Research Database. The included patients were categorized into three groups: (1) known diagnosis of AF (KAF) before the index stroke, (2) AFDAS, and (3) without AF (non-AF). Univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio (HR) for independent variables and recurrent IS, hemorrhagic stroke, or all-cause mortality. We identified 158,909 patients with IS of whom 16,699 (10.5%) had KAF and 7,826 (4.9%) had AFDAS. The patients with AFDAS were younger, more often male, and had lower CHA2DS2-VASc scores (3.8 ± 1.9 versus 4.9 ± 1.8, p < 0.001) than the patients with KAF. Anticoagulant treatment significantly reduced the risks of all outcomes. The standardized mortality rates were 40.4, 28.6, and 18.4 (per 100 person-years) for the patients with KAF, AFDAS, and non-AF, respectively. Compared with AFDAS, KAF was associated with lower risks of recurrent IS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86-0.97, p < 0.01] and hemorrhagic stroke (HR: 0.88, 95% CI: 0.79-0.99, p < 0.01) and a higher risk of all-cause mortality (HR: 1.11, 95% CI: 1.07-1.16, p < 0.001). The risks of recurrent IS and hemorrhagic stroke were higher and of all-cause mortality was lower for patients with AFDAS than with KAF. There is a strong need to refine treatment modalities to reduce the high mortality in patients with KAF and AFDAS.

In this study, we introduce a novel design of a remote edge-lit backlight structure featuring blue laser diodes (LDs). These LDs were integrated into a remote yellow phosphor layer on a light guide plate (LGP). Blue light emitted by the LDs passes through the LGP and spreads to the remote phosphor layer, generating white light output. Owing to the incorporation of a scattering layer between sequential LGPs, the remote edge-lit backlight structure facilitates the expansion of the output surface of the LGP by combining multiple individual LGPs. Two- and three-LGP remote edge-lit backlight structures demonstrated acceptable white illuminance uniformity. The proposed architecture serves as a viable solution for achieving uniform illumination in planar lighting systems using blue LDs; thus, this structure is particularly suitable for linear lighting or slender backlighting instead of display stand applications.

Background Smoking cessation reduces the risk of severe illnesses in the long run and contributes to improving health. This study evaluated the short-term and long-term effectiveness of workplace smoking cessation intervention implemented using the transtheoretical model. Methods Participants were assessed at baseline before the intervention and after 6 months and 4 years of follow-ups. Data on changes in participants’ perception of smoking prohibition in the workplace, knowledge of the hazards of smoking, attitude towards quitting smoking, and behavior related to tobacco harm prevention were collected. Results Results showed the prevalence of smoking cessation was 31.5% (95% CI: 25.4-38.1%) after 6 months and 10.7% (95% CI: 6.9-15.6%) after 4 years. At the abovementioned time points, the prevalence of second-hand smoke exposure, and the proportion of people who demonstrated correct knowledge of smoke hazards initially decreased and then increased. The proportion of participants who had seen or received information about tobacco harm prevention provided in the workplace increased from 75.6% at baseline to 95.6% (increased by 20.0%) after 6 months and finally to 97.2% (increased by 21.6%) after 4 years ( P < .001). However, the percentage of participants who hoped their workplace continued to provide smoking cessation services rose from 80.0% at baseline to 93.6% (increased by 13.6%) after 6 months and then fell to 78.0% (decreased by 2.0%) after 4 years ( P < .001). Conclusion The short-term effectiveness of the transtheoretical model in promoting workplace smoking cessation is substantial, but in the long-term, effectiveness weakens.

Abstract To increase expression levels of the PCV2 Cap(d41) protein, novel baculovirus surface display vectors with multiple expression cassettes were constructed to create recombinant baculoviruses BacSC-Cap(d41), BacDD-2Cap(d41), BacDD-3Cap(d41), and BacDD-4Cap(d41). Our results reveal that the recombinant baculovirus BacDD-4Cap(d41) was able to express the highest levels of Cap(d41) protein. Optimum conditions for expressing the PCV2 Cap(d41) protein were determined, and our results show that 107 of Sf-9 infected with the recombinant baculovirus BacDD-4Cap(d41) at an MOI of 5 for 3 days showed the highest level of protein expression. Mice immunized with the 4Cap(d41) vaccine which was prepared from the recombinant baculovirus-infected cells (107) elicited higher ELISA titers compared to the Cap (d41) vaccine. The 4Cap(d41) vaccine could elicit anti-PCV2 neutralizing antibodies and IFN-γ in mice, as confirmed by virus neutralization test and IFN-γ ELISA. Moreover, the swine lymphocyte proliferative responses indicated that the 4Cap(d41) vaccine was able to induce a clear cellular immune response. Flow cytometry analysis showed that the percentage of CD4+ T cells and CD4+/CD8+ ratio was increased significantly in SPF pigs immunized with the 4Cap(d41) vaccine. Importantly, the 4Cap(d41) vaccine induced an IFN-γ response, further confirming that its effect is through cellular immunity in SPF pigs. An in vivo challenge study revealed that the 4Cap(d41) and the commercial vaccine groups significantly reduce the viral load of vaccinated pigs as compared with the CE negative control group. Taken together, we have successfully developed a 4Cap(d41) vaccine that may be a potential subunit vaccine for preventing the disease associated with PCV2 infections.

Abstract Background The rate of preterm birth has been increasing worldwide. Most preterm babies are at an increased risk of central nervous system impairments as well as respiratory and gastrointestinal complications. The aim of this study was to investigate the epidemiologic characteristics of and associated factors contributing to preterm birth in Taiwan. Methods Information on obstetric antecedents and risk factors for preterm birth in pregnant women was obtained from the National Health Insurance Research (NHIR) database provided by the Taiwan National Health Research Institute. All live births from 2004 to 2013 in Taiwan were included in this study. Results A total of 130,362 live births from 2004 to 2013 were included in this study. Overall, the average annual rate of preterm births increased by 5.3% (from 3.33% in 2004 to 5.11% in 2013). Multiple logistic regression analyses showed that nulliparous women, multifetal pregnancies, advanced mother age, history of preterm birth, history of maternal drug abuse/dependence, and maternal medical complications were positively associated with an increased risk of preterm birth (all p-values

Purpose: Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors. GBMs with synchronous multiple foci (multiple GBMs) is rarely diagnosed in the clinical scenario. This study aims to compare the clinical characteristics between multiple and single GBMs and to identify factors associated with the survival of GBM and evaluate their effects. Methods: We retrospectively reviewed the medical records of patients with primary GBM in a referral medical center in Taiwan who were diagnosed between 2005 and 2016. They were identified from the cancer registry database of the center and followed from the date of diagnosis to october 2018. The primary endpoint of this study was overall survival (OS), and the independent factors for survival were identified through Cox regressions. Results: A total of 48 patients were identified, of whom 44 GBM (92%) and 4 gliosarcoma (GSM) (8%). Preoperative images showed five (10%) patients had multiple brain lesions. GSM showed a high ratio of multiple lesions (50%) than patients with GBM (5%) (p = 0.05). Those with multiple lesions had significantly worse median OS of 8.2 months compared to patients with a single lesion (16 months, p = 0.03). We found that multiple GBMs was a predictor of worse survival (hazard ratio [HR] = 3.57, 95% confidence interval [95%CI]: 1.26–10.13) after adjusting for other significant predictor of radiotherapy (HR = 0.47, 95%CI: 0.23–0.96). Conclusion: Patients with multiple GBMs had worse survival compared to those with single GBM. GBM patients without post-operative radiotherapy were also a predictor of worse survival. Keywords: Glioblastoma, Gliosarcoma, Multiple brain lesions, Radiotherapy, Survival

Background: Robot-assisted surgeries have been found to possess a number of advantages over conventional surgeries, and these benefits have promoted the expanded use of robot-assisted procedures in recent years, both in the numbers of procedures performed and the types of procedures to which robotic assistance is applied. This study sought to quantify this expanded use of robot-assisted surgeries over a 13-year period at a single surgeon in Taiwan. Materials and Methods: We retrospectively reviewed a total of 2000 patients who underwent robot-assisted urologic surgeries between December of 2005 and August of 2018. For the purposes of statistical comparison, we divided this 13-year period into four subperiods and classified the surgeries into eight types depending on the body part or parts upon which they were performed. Results: The total number of surgeries in the first, second, third, and fourth subperiods was 124, 173, 738, and 965, respectively; this represented a significant increase in the total number of robot-assisted urologic surgeries performed across the four subperiods. In addition, there were also significant increases in the numbers of surgeries for seven of the eight categories of surgeries across the four subperiods. Conclusion: These results show that our institution's experience with robot assistance in urological surgeries from 2005 to 2018 was consistent with the generally expanded use of such assistance documented by earlier studies, with both the numbers and types of robot-assisted surgeries performed increasing significantly over that period.

Paraneoplastic leukemoid reaction (PLR) is exceedingly uncommon syndrome in oral cancer and has implicated a worse outcome. This report describes a case of buccal mucosa cancer encountered PLR syndrome during the course of tumor progression. We conduct a literature review to highlight the relationship between PLR and the outcome in oral cancer. PLR is associated with rapid tumor growth and worse outcome in head-and-neck cancer.

Diabetes mellitus (DM) is an important risk factor in patients with end-stage renal disease (ESRD). DM is associated with the development of cardiovascular diseases, such as atrial fibrillation (AF), due to poor glycemic control. However, few studies have focused on the risk of developing ESRD among DM patients with and without AF. This study evaluated ESRD risk among DM patients with and without AF in Taiwan. Data were retrieved from one million patients randomly sampled from Taiwan's National Health Insurance Research Database, including 6,105 DM patients with AF propensity score-matched with 6,105 DM patients without AF. Both groups were followed until death, any dialysis treatment, or December 31, 2013, whichever occurred first. AF was diagnosed by a qualified physician according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), using the diagnostic code 427.31. Patients aged

Our previous reports proved that the structural protein σA of avian reovirus (ARV) is an energy activator which can regulate cellular metabolism that is essential for virus replication. This study has further demonstrated that the ARV protein σA is able to upregulate the HIF-1α/myc/glut1 pathway in three cancer cell lines (A549, B16-F10, and HeLa) to alter the metabolic pathway of host cells. Quantitative real-time RT-PCR and Western blotting results have revealed that σA protein could enhance both mRNA and the protein levels of HIF-1α, c-myc, and glut1 in these cancer cell lines. In this work, ATeam immunofluorescence staining was used to reveal that knockdown of HIF-1α, c-myc, and glut1 by shRNAs decreased cellular ATP levels. Our data reveal that the ARV σA protein can downregulate lactate fermentation and upregulate glutaminolysis. The σA protein upregulates glutaminase, which converts glutamate into the TCA cycle intermediate α-ketoglutarate, activating the TCA cycle. In the lactate fermentation pathway, ARV σA protein suppresses lactate dehydrogenase A (LDHA), implying the Warburg effect does not occur in these cancer cell lines. This study provides a novel finding revealing that ARV σA protein upregulates glycolysis and glutaminolysis to produce energy using the HIF-1α/c-myc/glut1 pathway to benefit virus replication in these cancer cell lines.

Abstract Background This study aimed to investigate the occurrence and risk factors of thyroid dysfunction (TD) in patients with chronic hepatitis C (CHC) infection in Taiwan. Methods The data in this study were obtained from the Taiwan National Health Insurance Research (Taiwan NHIR) database between 2001 and 2013. CHC patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) were enrolled as case patients, and nontreated CHC patients were enrolled as controls and were matched at a control:case ratio of 3:1 by index date, age (± 3 years), and sex. We compared the cumulative incidence of TD between the cohorts at follow-up until 2013. Results During the study period, 3810 cases and 9393 controls were included in the study. Among the study subjects, 173 (4.5%) case patients and 244 (2.6%) controls were diagnosed with TD during the follow-up period. The types of TD were hypothyroidism (42.9%), hyperthyroidism (31.2%), and thyroiditis (25.9%). Compared to controls during the 13-year follow-up, patients treated with PEG-IFN/RBV had a higher incidence rate of TD (P

Objective: Erectile dysfunction (ED) is a major complication of radical prostatectomy. Despite advances in surgical techniques, the postoperative continence and potency rates are still not satisfactory. Many studies have reported experiences with penile rehabilitation using tadalafil for patients receiving nerve-sparing robotic-assisted radical prostatectomy, but similar reports are still lacking in Taiwan. Patients and Methods: We collected 163 patients that had undergone unilateral or bilateral nerve-sparing robotic-assisted radical prostatectomy from January 2013 to December 2014 in Tungs' Hospital. One month after operation, 5 mg tadalafil once daily was prescribed for 54 patients whose Foley's catheter had been removed and who had ED. We recorded the International Index of Erectile Function (IIEF-5) score at the 12th month after surgery. We defined postsurgery IIEF-5 ≥22 as potency or no ED. We compared the differences in clinical parameters and postsurgery potency rates between patients with or without tadalafil treatment. Results: The postsurgery potency rates of those with tadalafil treatment were significantly higher than that of those without tadalafil treatment (55.6% vs. 32.1%) after a 1-year follow-up observation. The mean (standard deviation) of IIEF-5preamong those with and without tadalafil treatment was 21.3 (4.5) and 19.2 (4.2), respectively. There were no significant differences in baseline clinical condition parameters between patients with potency with or without tadalafil treatment. The results indicated that the tadalafil-treated patients had a higher odds ratio (OR) of potency (adjusted OR = 2.58, 95% confidence interval [CI] = 1.28–5.22) than the nontadalafil-treated patients. However, those ≥65 years old were associated with a lower potency rate (adjusted OR = 0.94, 95% CI = 0.89-0.99). Conclusion: Starting penile rehabilitation with tadalafil 5 mg daily 1 month after nerve-sparing radical prostatectomy is safe for patients. Patients with mild-to-moderate ED should use tadalafil 5 mg daily after receiving nerve-sparing robotic-assisted laparoscopic prostatectomy due to its significant benefit in erectile function recovery.

While Parkinson’s disease (PD) and attention-deficit hyperactivity disorder (ADHD) are two distinct conditions, it has been hypothesized that they share several overlapping anatomical and neurochemical changes. In order to investigate that hypothesis, this study used claims data from Taiwan’s Longitudinal Health Insurance Database 2000 to provide the significant nationwide population-based evidence of an increased risk of PD among ADHD patients, and the connection between the two conditions was not the result of other comorbidities. Moreover, this study showed that the patients with PD were 2.8 times more likely to have a prior ADHD diagnosis compared with those without a prior history of ADHD. Furthermore, an animal model of ADHD was generated by neonatally injecting rats with 6-hydroxydopamine (6-OHDA). These rats were subjected to behavior tests and the 99mTc-TRODAT-1 brain imaging at the juvenile stage. Compared to control group rats, the 6-OHDA rats showed a significantly reduced specific uptake ratio in the striatum, indicating an underlying PD-linked pathology in the brains of these ADHD phenotype-expressing rats. Overall, these results support that ADHD shares a number of anatomical and neurochemical changes with PD. As such, improved knowledge of the neurochemical mechanisms underlying ADHD could result in improved treatments for various debilitating neurological disorders, including PD.

Limited studies have evaluated risk of stroke associated with the use of NSAIDs in patients with end-stage kidney disease. We examined the adverse effects of selective and nonselective NSAID use on the risk of stroke in dialysis patients. Methods: A case-crossover study was conducted using medical claims data from the National Health Insurance Research Database in Taiwan. We identified patients with ischemic and hemorrhagic stroke (defined as International Classification of Diseases, 9th revision, Clinical Modification codes 433, 434, and 436 for ischemic stroke and 430 and 431 for hemorrhagic stroke) from inpatient claims during the period from 2003 to 2012. Conditional logistic regression models with adjustment for potential confounders were used to determine the effects of NSAID use on stroke. Results: A total of 1190 dialysis patients with stroke were identified from 2003 to 2012. The results indicate a 1.31-fold increased risk of stroke related to NSAID use during the 30 days prior to a stroke (AOR = 1.31; 95% CI: 1.03–1.66); likewise, an excessive risk of ischemic stroke was observed (AOR = 1.34; 95% CI: 1.02–1.77). When classifying NSAIDs into selective and nonselective groups, nonselective NSAID use was significantly associated with an increased risk of stroke (AOR = 1.27; 95% CI: 1.00–1.61). Discussion: In summary, the results show supportive evidence that NSAID use increased the risk of stroke in dialysis patients, which suggests the importance of closely monitoring the transient effects of initial NSAID treatment to patients on dialysis.

Background: To evaluate the efficacy of early dutasteride administration in patients with a detectable prostate-specific antigen (PSA) levels after robot-assisted radical prostatectomy (RARP).Methods: We retrospectively analyzed RARP patients whose pathological stage is T2a to T3b without lymph node or distant metastasis from 2007 to 2017. All patients received a daily dose of 0.5 mg of dutasteride when post-RARP PSA levels were increasing but had not achieved biochemical recurrence. PSA levels were monitored every 3 months after dutasteride administration. None of the patients received radiotherapy (RT) or androgen-deprivation therapy (ADT) before taking dutasteride. All follow-ups were begun from RARP to January 2019 or to the date of RT/ADT.Results: Thirty-five patients were included in this analysis. The median followed up was 53.6 months. Twenty-two patients (62.9%) showed a PSA response in which the PSA decreased more than 10% at the first follow-up after dutasteride administration. The Pathological stage > T2 (p = 0.012) and positive surgical margin (p = 0.046) were prognostic factors for a PSA response. Twenty-three out of 35 included patients (65.7%) did not require further RT/ADT. The significant risk factor was the PSA level (p = 0.011) at the beginning of dutasteride treatment. The cut-off value of the PSA level to avoid further RT/ADT was 0.195 ng/ml.Conclusions: Early dutasteride administration showed a significant decline in the PSA levels of patients with pathology stage >T2 and positive surgical margin in our retrospective hypothesis-generating study. If dutasteride was provided before the PSA value increased to 0.195 ng/ml after RARP, it would reduce the probability of acquirement of RT/ADT.

The prevalence of temporomandibular disorder (TMD) among elderly people with Parkinson's disease (PD) is relatively high, but a population-based study of the relationship between PD and TMD is still lacking. This study, therefore, sought to investigate the association between TMD and PD by using data for one million randomly sampled beneficiaries of Taiwan's National Health Insurance program, including 6,185 PD patients who were matched through propensity score matching with 18,555 non-PD patients. Both the PD and non-PD cohorts were followed until death, any diagnosis of TMD, or December 31, 2013, whichever occurred first. Each diagnosis of TMD was made by a qualified physician according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), using the diagnosis codes 524.60, 524.62, 524.63, and 524.69 while excluding tooth abscess, wisdom tooth eruption, herpes zoster and postherpetic neuralgia, mastoiditis, otitis externa, otitis media, parotitis, sialadenitis, and trigeminal neuralgia. We used Cox proportional hazard regression models to calculate the relative risk of TMD and found a 2.11-fold (95% CI: 1.35-3.30) increased risk of TMD overall in the PD group compared with the non-PD group. Stratified by follow-up period, there was a 4.25-fold (95% CI: 1.51-11.93) increased risk in the PD group in the first year after the initial PD diagnosis and a 3.88-fold (95% CI: 1.33-11.28) increased risk in the second year. Over the long-term (>5 years), PD was significantly associated with an increased risk of TMD. These findings suggest that it is important to closely monitor the temporomandibular joint health of PD patients.

Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS.

Psoriasis is an immune-mediated inflammatory disease that affects 2% to 3% of the world population. Alantolactone, a sesquiterpene lactone, was isolated from Inula helenium and Radix inulae and has several biological effects, including antifungal, anthelmintic, antimicrobial, anti-inflammatory, antitrypanosomal, and anticancer properties. This study aimed to evaluate the antipsoriatic potential of alantolactone in vitro and in vivo and to explore its underlying mechanisms. These results showed that alantolactone significantly attenuated IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokine-induced hyperproliferation in HaCaT keratinocytes. Moreover, M5 cytokines significantly upregulated the mRNA levels of TNF-α, IL-6, IL-1β, and IL-8. However, alantolactone attenuated the upregulation of these inflammatory cytokines. In addition, alantolactone was found to inhibit STAT3 phosphorylation and NF-κB p65 nuclear translocation in HaCaT keratinocytes. Furthermore, alantolactone treatment in mice significantly alleviated the severity of skin lesions (erythema, scaling and epidermal thickness, and inflammatory cell infiltration) and decreased the mRNA expression of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, IL-8, IL-17A, and IL-23) in an IMQ-induced-like mouse model. Therefore, our new findings revealed that alantolactone alleviates psoriatic skin lesions by inhibiting inflammation, making it an attractive candidate for future development as an antipsoriatic agent.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the production of β2-glycoprotein I (β2GPI)-dependent autoantibodies, with vascular thrombosis or obstetrical complications. Around 20% of APS patients are refractory to current treatments. Crassolide, a cembranoid diterpene extracted from soft corals, is a potential therapeutic candidate. Here, to examine the anti-inflammatory properties of crassolide, we first determined its effects on bone marrow-derived and splenic dendritic cells (DC). Specifically, we applied lipopolysaccharide (LPS) or β2GPI stimulation and measured the expressions of CD80 and CD86, and secretions of cytokines. We also determined in the OT-II mice, if bone marrow-derived DC was able to stimulate antigen-specific T cells. Moreover, we examined the therapeutic potential of crassolide postimmunization in a murine model of APS that depended on active immunization with β2GPI. The vascular manifestations were evaluated in terms of fluorescein-induced thrombi in mesenteric microvessels, whereas the obstetric manifestations were evaluated based on the proportion of fetal loss after pregnancy. We also measured blood titers of anti-β2GPI antibody, splenic cell proliferative responses and cytokine secretions after β2GPI stimulation ex vivo. Finally, we determined in these mice, hematological, hepatic and renal toxicities of crassolide. Crassolide after LPS stimulation suppressed DC maturation and secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and IL-23, and downstream T cell activation. Crassolide could partially ameliorate both the vascular and obstetric manifestations of APS in BALB/c mice. Both blood titers of anti-β2GPI antibody and splenic cell proliferation after β2GPI stimulation were reduced. Splenic Th1 and Th17 responses were also lowered after β2GPI stimulation. Finally, within therapeutic doses of crassolide, we found no evidence of its toxicity. In conclusion, we showed the ability of crassolide to suppress DC and downstream T cell responses. Crassolide is therefore a potential candidate for adjunctive therapy in APS.

ABSTRACT Enterovirus A71 (EV-A71) infections are one of the main etiological agents of hand, foot and mouth disease (HFMD) and herpangina worldwide. EV-A71 infection is a life-threatening communicable disease and there is an urgent global need for the development of vaccines for its prevention and control. The morbidity rate of EV-A71 infection differs between countries. The pathogen’s genetic lineages are undergoing rapid evolutionary changes. An association between the occurrence of EV-A71 infection and the circulation of different genetic strains of EV-A71 virus has been identified around the world. In this review, we present and discuss the molecular epidemiology and pathogenesis of the human disease caused by EV-A71 infection, as well as current prospects for the development of an EV-A71 vaccine.

Background Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.

Transplant tourism has increased rapidly in the past two decades, accounting for about 10% of world organ transplants. However it is ethically controversial and discouraged by professional guidelines. We conducted this study to investigate the outcomes and trends of overseas kidney and liver transplantation in Taiwan to provide a sound basis for ethical reflection.The Taiwanese National Health Insurance Research Database was used to identify 2381 domestic and 2518 overseas kidney transplant (KT) recipients from 1998 to 2009 and 1758 domestic and 540 overseas liver transplantation (LT) recipients from 1999 to 2009. Cox proportional hazards models were used to assess the risks of mortality and graft failure. The numbers of overseas transplantation increased after 2000, reached a peak in 2005 and decreased after 2007. Compared to their domestic counterparts, the overseas KT recipients were older, male predominant, with shorter pre-op dialysis period and more comorbidities. Similarly, the overseas LT recipients were older, male predominant and had more hepatocellular carcinoma cases. The 1-, 5-, and 10-year patient survival rates were 96.9%, 91.7% and 83.0% respectively for domestic KT and 95.8%, 87.8% and 73.1% for overseas KT (p

PURPOSE:Minimal axial diameter (MIAD) in magnetic resonance imaging (MRI) was recognized as the most useful parameter in diagnosing lateral retropharyngeal lymph (LRPL) nodes in nasopharyngeal carcinoma (NPC). This study aims to explore the additional nodal parameters in MRI and positron emission tomography-computed tomography for increasing the prediction accuracy. MATERIALS AND METHODS:A total of 663 LRPL nodes were retrospectively collected from 335 patients with NPC. The LRPL nodes ascertained on follow-up MRI were considered positive for metastases. First, the optimal cutoff value of each parameter was derived for each parameter. In addition, neural network (NN) nodal evaluation was tested for all combinations of three parameters, namely MIAD, maximal axial diameter (MAAD), and maximal coronal diameter (MACD). The optimal approach was determined through brute force attack, and the results of two methods were compared using a bootstrap sampling method. Second, the mean standard uptake value (NSUVmean) was added as the fourth parameter and tested in the same manner for 410 nodes in 219 patients. RESULTS:In first and second analysis, the accuracy rate (percentage) for the MIAD was 89.0% (590/663) and 89.0% (365/410), with the optimal cutoff values being 6.1 mm and 6.0 mm, respectively. With the combination of all three and four parameters, the accuracy rate of the NN was 89% (288/332) and 88.8% (182/205), respectively. In prediction, the optimal combinations of the three and four parameters resulted in correct identification of three (accuracy: 593/663, 89.4%) and six additional nodes (371/410, 90.5%), representing 4% (3/73) and 13.3% (6/45) decreases in incorrect prediction, respectively. CONCLUSION:NPC LRPL nodes with an MIAD ≥ 6.1 mm are positive. Among nodes with an MIAD < 6.1 mm, if the NSUVmean ≥ 2.6 or MACD ≥ 25 mm and MAAD ≥ 8 mm, the nodes are positive; otherwise, they are negative.

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

Background/Aim: Hashimoto thyroiditis (HT) association with thyroid lymphoma is well established; however, the association with papillary thyroid cancer (PTC) is still unclear. Thyroid cancer incidence has shown an increasing trend in recent years. It is characterized by slow growth, making it generally amenable to successful treatment. Materials and Methods: We aimed to identify genes considered as promising biomarkers of the progression from thyroiditis to thyroid cancer in public gene expression datasets. Results: We identified 70 differentially expressed genes (DEGs) and used them to prioritize biological risk genes for thyroiditis and thyroid cancer. Statistics and a scoring system based on six functional annotations of significant biological impact identified four genes of interest: CXCR4, IL6ST, PPARG and TP53. Kaplan–Meier plots were used to assess the expression levels related to overall survival. Furthermore, a manual bibliographic search was carried out for each gene, and a protein–protein interaction (PPI) network was built to verify their known associations. Conclusion: The results showed that all four genes (CXCR4, IL6ST, PPARG, TP53) were highly relevant to thyroiditis and thyroid cancer, thus making them worthy of further investigation to understand their relationship with these two diseases. [ABSTRACT FROM AUTHOR]