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Abstract This population-based study investigated the risk of having had prior herpes zoster within five years preceding a diagnosis of head and neck cancer. We conducted a case-control study that included 9,191 patients with a diagnosis of head and neck cancer in Taiwan’s Longitudinal Health Insurance Database 2010 and 36,764 matched controls. We assessed the odds of patients with head and neck cancer having had a diagnosis of herpes zoster during the five years preceding head and neck cancer using multiple logistic regression analysis. The prevalence of prior herpes zoster among the total sample was 4.6%, 7.9% and 3.8% among patients with and without head and neck cancer, respectively (p

Abstract Aims/Introduction Electronegative low‐density lipoprotein (L5) is the most atherogenic fraction of low‐density lipoprotein and is elevated in people with metabolic syndrome (MetS), whereas the retinol‐binding protein 4 receptor (stimulated by retinoic acid 6 [STRA6]) cascade is disrupted in various organs of patients with obesity‐related diseases. Our objective was to investigate whether L5 from MetS patients capably induces pathogenesis of aorta through disrupting the STRA6 cascade. Material and Methods We examined the in vivo and in vitro effects of L5 on the STRA6 cascade and aortic atherogenic markers. To investigate the role of this cascade on atherosclerotic formation, crbp1 transfection was carried out in vitro. Results This study shows that L5 activates atherogenic markers (p38 mitogen‐activated protein kinases, pSmad2 and matrix metallopeptidase 9) and simultaneously suppresses STRA6 signals (STRA6, cellular retinol‐binding protein 1, lecithin‐retinol acyltransferase, retinoic acid receptor‐α and retinoid X receptor‐α) in aortas of L5‐injected mice and L5‐treated human aortic endothelial cell lines and human aortic smooth muscle cell lines. These L5‐induced changes of the STRA6 cascade and atherogenic markers were reversed in aortas of LOX1−/− mice and in LOX1 ribonucleic acid‐silenced human aortic endothelial cell lines and human aortic smooth muscle cell lines. Furthermore, crbp1 gene transfection reversed the disruption of the STRA6 cascade, the phosphorylation of p38 mitogen‐activated protein kinases and Smad2, and the elevation of matrix metallopeptidase 9 in L5‐treated human aortic endothelial cell lines. Conclusions This study shows that L5 from MetS patients induces atherogenic markers by disrupting STRA6 signaling. Suppression of STRA6 might be one novel pathogenesis of aorta in patients with MetS.

Poloxamer-188 (P188) is a nonionic triblock linear copolymer that can be used as a pharmaceutical excipient because of its amphiphilic nature. This study investigated whether P188 can act as an adjuvant to improve the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) subunit vaccine. BALB/c mice were vaccinated twice with the RBD antigen alone or in combination with P188 or MF59 (a commercial adjuvant for comparison purposes). The resulting humoral and cellular immunity were assessed. Results showed that P188 helped elicit higher neutralizing activity than MF59 after vaccination. P188 induced significant humoral immune response, along with type 1 T helper (Th1) and type 2 T helper (Th2) cellular immune response when compared with MF59 due to repressing p38MAPK phosphorylation. Furthermore, P188 did not result in adverse effects such as fibrosis of liver or kidney after vaccination. In conclusion, P188 is a novel adjuvant that may be used for safe and effective immune enhancement of the SARS-CoV-2 RBD antigen.

Abstract Background Several studies examined headaches as a symptom of brain neoplasms. Nevertheless, very few studies attempted to specifically evaluate the role of headaches as a risk factor. This study aimed to investigate the risk of migraine occurrence in the preceding years among patients diagnosed with brain tumors and unaffected controls. Methods Data were obtained from the Taiwan National Health Insurance Research Database. In total, 11,325 adults with a first-time brain tumor diagnosis were included as cases, together with 11,325 unaffected matched controls. Each individual was traced in the healthcare claims dataset for a prior diagnosis of migraines. Conditional logistic regressions were performed to calculate the odds ratio (OR) and the corresponding 95% confidence interval (CI) to present the association between brain tumors and having previously been diagnosed with migraines. Results We found that among patients with and those without brain tumors, 554 (4.89%) and 235 (2.08%) individuals, respectively, were identified as having a prior migraine diagnosis. Compared to unaffected controls, patients with brain tumors experienced an independent 2.45-fold increased risk of having a prior migraine diagnosis. The risks were even higher among men (odds ratio (OR) = 3.04, 95% confidence interval (CI) = 2.29~ 4.04) and after patients who had received a prior migraine diagnosis within 3 years were excluded (OR = 1.91, 95% CI = 1.59~ 2.29). Conclusions This is the first report demonstrating the occurrence of brain tumors to be associated with a prior migraine history, for both men and women, in a population-based study.

The epicardial adipose tissue (EAT), mainly composed of brown adipose tissue, is a metabolically active tissue releasing various bioactive factors with a critical role in metabolic diseases. The EAT is often irradiated during radiotherapy in patients with esophageal cancer due to its proximity to the target region. We aimed to evaluate the effect of radiation to the EAT on survival outcomes in patients with esophageal cancer receiving neoadjuvant chemoradiotherapy followed by esophagectomy. We analyzed data on 36 patients with esophageal cancer treated with trimodal therapy between 2012 and 2017. The median follow-up period was 22.0 months. The 3-year overall survival and progression-free survival rates were 39.7% and 32.5%, respectively. Multivariate analysis revealed that higher EAT-REI was independently associated with worse overall survival (hazard ratio: 1.002, p = 0.028) and progression-free survival (hazard ratio: 1.002, p = 0.03). The cutoff value with the highest accuracy for avoiding mortality was EAT-REI = 68.8 cGy/mL (area under the curve, 0.78, p = 0.006). The 3-year overall survival rate in patients with EAT-REI ≥68.8 and p = 0.003). The EAT should be considered an organ at risk during radiotherapy in patients with esophageal cancer. EAT-REI might serve as a biomarker of survival outcomes in these patients.

Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. “Stimulated by retinoic acid 6” (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1−/− mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease.

Background: Limited data are available on the management of esophageal perforations in elderly patients. The aim of this study is to analyze the characteristics and treatments of esophageal perforations in elderly patients. Methods: Data on patients with esophageal perforations and older than 65 years of age were retrospectively reviewed from January 2001 to November 2012. Surgery-related and caustic-induced perforations were excluded in this study. Disease-related parameters, such as sex, bacteriology, locations, time to treatment, treatment types, and outcomes, were analyzed. A new method, cervical esophageal ligation and T-tube diversion following repair of esophageal perforations, was introduced. Results: A total of 61 patients, 24 females and 37 males, were eligible for this study. Heterogeneous presentations were noted following diagnosis of esophageal perforations. Esophagoscopy was the most frequently used method for diagnosis of esophageal perforations. Different sites of perforations would induce heterogeneous complications, among which thoracic perforations were most lethal. In this study, disease-related mortality rate was 13.1% (8 patients). Thoracic and abdominal perforations (p 48 hours (p = 0.002) were two significant factors responsible for mortality of patients esophageal perforations. The suggested new diversion method can be used as a salvage treatment option for complicated perforations. Conclusion: Early diagnosis and prompt treatments are the important determinants to reduce mortalities of elderly patients with esophageal perforations. Cervical esophageal ligation combined with T-tube diversion can be considered as a salvage method for complicated perforations.

Introduction: Currently, the percutaneous puncture method is a popular method for performing tracheostomies. However, unexpected bleeding or organ injury is a concern with this method because the dissection or dilatation is blind. A con- ventional open surgical tracheostomy (COST) usually takes more time to complete, but the procedure has a lower risk of bleeding compared to blind method used in the percutaneous puncture approach. In this study, we evaluated a fast open surgical tracheostomy (FOST) procedure, which combines the advantages of both open and percutaneous methods. Materials and Methods: From January 1, 2009, to December 31, 2010, our team performed surgeries on 259 patients in our institution that were indicated for tracheostomy. During this period, both COST and FOST methods were performed. These patients were not randomized with regard to method. No additional or specialized tools are required in the FOST method. All operations were performed by a single surgeon. The operative details and outcomes were analyzed. Results: One hundred and fifty-six patients underwent COST, while 103 patients underwent FOST. There was no differ- ence in gender distribution, age and indications for surgery in either group. The operative time was much faster in FOST than in COST. There was no acute or delayed bleeding in either group. Minor stoma infection was seen in five patients in the FOST group and 12 patients in the COST group. Conclusion: The FOST provided a faster alternative to COST, while preserving the techniques of open dissection and resulting in comparable outcomes. [Arch Clin Exp Surg 2015; 4(1.000): 36-40]

Patients with gastroesophageal reflux disease (GERD) present with comorbid complications with implications for healthcare utilization. To date, little is known about the effects of GERD treatment with a proton-pump inhibitor (PPI) on patients' subsequent healthcare utilization for acute respiratory infections (ARIs). This population-based study compared ARI episodes captured through outpatient visits, one year before and one year after GERD patients received PPI treatment. We used retrospective data from the Longitudinal Health Insurance Database 2005 in Taiwan, comparing 21,486 patients diagnosed with GERD from 2010 to 2012 with 21,486 age-sex matched comparison patients without GERD. Annual ARI episodes represented by ambulatory care visits for ARI (visits during a 7-day period bundled into one episode), were compared between the patient groups during the 1-year period before and after the index date (date of GERD diagnosis for study patients, first ambulatory visit in the same year for their matched comparison counterpart). Multiple regression analysis using a difference-in-difference approach was performed to estimate the adjusted association between GERD treatment and the subsequent annual ARI rate. We found that the mean annual ARI episode rate among GERD patients reduced by 11.4%, from 4.39 before PPI treatment, to 3.89 following treatment (mean change = -0.5 visit, 95% confidence interval (CI) = (-0.64, -0.36)). In Poisson regression analysis, GERD treatment showed an independent association with the annual ARI rate, showing a negative estimate (with p

Associations of hepatitis C virus infection with Alzheimer's disease have not been studied among higher risk, bipolar disorder patients. This population-based case-control study investigated the risks of hepatitis C virus infection among Alzheimer's disease patients with bipolar disorder in the years preceding their Alzheimer's disease diagnosis. We used 2000-2013 data from the Longitudinal Health Insurance Database in Taiwan. Among patients with bipolar disorder, 73 were diagnosed with Alzheimer's disease (cases), who were compared with 365 individuals with bipolar disorder but without Alzheimer's disease (randomly selected controls matched on sex, age, and index year with cases). Prior claims (before the diagnosis year/index year for controls) were screened for a diagnosis of hepatitis C virus infection. Conditional logistic regression models were used for analysis. We found that 23 (31.51%) and 60 (16.44%) patients with bipolar disease were identified with a hepatitis C diagnosis among those with and without Alzheimer's disease, respectively. Compared to controls, patients with Alzheimer's disease showed 2.31-fold (95% confidence interval = 1.28-4.16) increased risk of hepatitis C infections adjusted for demographics and socio-economic status. Findings suggest an association of Alzheimer's disease with a preceding diagnosis of hepatitis C infection among patients with bipolar disorder. Findings may suggest a need for increased awareness of and appropriate surveillance for Alzheimer's disease in patients with bipolar disorder diagnosed with hepatitis C infection.

The etiology of chronic urticaria (CU) is diverse, with chronic infections and inflammation being reported as considerable contributing factors. Although the prevalence of metabolic syndrome was found to be significantly elevated in patients with CU, no one has specifically estimated the effects on CU following hyperlipidemia. This study aimed to examine the association between hyperlipidemia and CU using a population-based dataset in Taiwan. This study included 9798 adults with CU as cases and 9798 sex- and age-matched controls. These patients were examined for whether they had received a prior diagnosis of hyperlipidemia. We used conditional logistic regression analyses to calculate the odds ratio (OR) and its corresponding 95% confidence interval (CI) for having been previously diagnosed with hyperlipidemia between cases and controls. In total, 7066 (36.1%) patients had received a prior diagnosis of hyperlipidemia, including 4287 (43.8%) among CU cases and 2779 (28.4%) among controls. The conditional logistic regression revealed that the OR of prior hyperlipidemia for cases was 1.97 (95% CI: 1.85~2.09) compared to the controls. Furthermore, compared to patients without CU, patients with CU independently experienced a 1.65-fold (95% CI = 1.55~1.76; p

Although the vermiform appendix is commonly considered a vestigial organ, adverse health consequences after an appendectomy have garnered increasing attention. In this study, we investigated the risks of gallstone occurrence during a 5-year follow-up period after an appendectomy, using a population-based dataset. We used data from the Taiwan Longitudinal Health Insurance Database 2005. The exposed cohort included 4916 patients who underwent an appendectomy. The unexposed cohort was retrieved by randomly selecting 4916 patients matched with the exposed cohort in terms of sex, age, and year. We individually tracked each patient for a 5-year period to identify those who received a diagnosis of gallstones during the follow-up period. Cox proportional hazard regressions were performed for the analysis. During the 5-year follow-up period, the incidence rate per 1000 person-years was 4.71 for patients who had undergone an appendectomy, compared to a rate of 2.59 for patients in the unexposed cohort (p

Prior studies indicate a possible association between depression and cholecystectomy, but no study has compared the risk of post-operative depressive disorders (DD) after cholecystectomy. This retrospective follow-up study aimed to examine the relationship between cholecystectomy and the risk of DD in patients with gallstones in a population-based database.Using ambulatory care data from the Longitudinal Health Insurance Database 2000, 6755 patients who received a first-time principal diagnosis of gallstones at the emergency room (ER) were identified. Among them, 1197 underwent cholecystectomy. Each patient was then individually followed-up for two years to identify those who were later diagnosed with DD. Cox proportional hazards regressions were performed to estimate the risk of developing DD between patients with gallstone who did and those who did not undergo cholecystectomy.Of 6755 patients with gallstones, 173 (2.56%) were diagnosed with DD during the two-year follow-up. Among patients who did and those who did not undergo cholecystectomy, 3.51% and 2.36% later developed depressive disorder, respectively. After adjusting for the patient's sex, age and geographic location, the hazard ratio (HR) of DD within two years of gallstone diagnosis was 1.43 (95% CI, 1.02-2.04) for patients who underwent cholecystectomy compared to those who did not. Females, but not males, had a higher the adjusted HR of DD (1.61; 95% CI, 1.08-2.41) for patients who underwent cholecystectomy compared to those who did not.There is an association between cholecystectomy and subsequent risk of DD among females, but not in males.

BackgroundThe majority of previous studies investigating the health care utilization of people with dementia were conducted in Western societies. There is little information on the economic burden on the healthcare system attributable to dementia in Asian countries. This study thus investigated differences in utilization of healthcare services between subjects with and those without a diagnosis of dementia using Taiwan's National Health Insurance population-based database.MethodsThis study comprised 5,666 subjects with a dementia diagnosis and 5,666 age- and gender-matched comparison subjects without a dementia diagnosis. We individually followed each subject for a 1-year period starting from their index date to evaluate their healthcare resource utilization. Healthcare resource utilization included the number of outpatient visits and inpatient days, and the mean costs of outpatient and inpatient treatments. In addition, we divided healthcare resource utilization into psychiatric and non-psychiatric services.ResultsAs for utilization of psychiatric services, subjects with a dementia diagnosis had significantly more outpatient visits (2.2 vs. 0.3, pConclusionsWe concluded that subjects who had received a clinical dementia diagnosis had significantly higher utilization of all healthcare services than comparison subjects.

A growing list of microRNAs (miRNAs) show aberrant expression patterns in hepatocellular carcinoma (HCC), but the regulatory mechanisms largely remain unclear. RNA editing catalyzed by members of the adenosine deaminase acting on the RNA (ADAR) family could target the miRNA precursors and affect the biogenesis process. Therefore, we investigate whether RNA editing could be one mechanism contributing to the deregulation of specific miRNAs in HCC. By overexpression of individual ADARs in hepatoma cells, RNA editing on the precursors of 16 miRNAs frequently deregulated in HCC was screened by a sensitive high-resolution melting platform. The results identified RNA precursors of miR-214 and miR-122 as potential targets edited by ADAR2. A subset of HCC showing elevated ADAR2 verified the major editings identified in ARAR2 overexpressed hepatoma cells, either with A-to-I or U-to-C changes. The unusual U-to-C editing at specific residues was demonstrated as being attributed to the A-to-I editing on the RNA transcripts complementary to the pri-miRNAs. The editing event caused a decrease of the RNA transcript complementary to pri-miR-214, which led to the decrease of pri-miR-214 and miR-214 and resulted in the increased protein level of its novel target gene Rab15. In conclusion, the current study discovered ADAR2-mediated editing of the complementary antisense transcripts as a novel mechanism for regulating the biogenesis of specific miRNAs during hepatocarcinogenesis.

We prove two new fixed point theorems in the framework of partially ordered metric spaces. Our results generalize and improve many recent fixed point theorems in the literature.

For a tvs-G-cone metric space (𝑋,𝐺) and for the family 𝒜 of subsets of X, we introduce a new notion of the tvs-ℋ-cone metric ℋ with respect to G, and we get a fixed result for the 𝒞ℬ𝒲-tvs-G-cone-type function in a complete tvs-G-cone metric space (𝒜,ℋ). Our results generalize some recent results in the literature.

By using the stronger Meir-Keeler mapping, we introduce the concepts of the sMK-G-cyclic mappings, sMK-K-cyclic mappings, and sMK-C-cyclic mappings, and then we prove some best proximity point theorems for these various types of contractions. Our results generalize or improve many recent best proximity point theorems in the literature (e.g., Elderd and Veeramani, 2006; Sadiq Basha et al., 2011).