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BACKGROUND AND AIMS Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH AND RESULTS Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P

Objectives To determine the bidirectional relationship between macrophage activation syndrome (MAS) and SLE. Methods Using the 1997–2013 Taiwan National Health Insurance Research Database, we identified patients with newly diagnosed SLE from 2001 to 2013 and selected individuals without SLE from a 1 million representative population. Propensity score (PS) matching was performed to balance incident SLE patients and individuals without SLE according to age, sex, comorbidities and medical utilization. The association between a history of MAS and SLE was studied using conditional logistic regression analysis shown as an adjusted odds ratio (aOR). The risk of MAS associated with SLE was analysed using Cox proportional regression analysis, shown as an adjusted hazard ratio (aHR), and we conducted a sensitivity analysis using various definitions of MAS. Results We included 10 481 SLE patients and 20 962 PS-matched (1:2) non-SLE individuals. The correlation between a history of MAS and SLE did not reach statistical significance after adjustment for potential confounders [aOR 1.18 (95% CI, 0.80, 1.75)] in the age-/sex-matched populations. In the 1:2 PS-matched populations, the risk of MAS markedly increased in patients with SLE [aHR 7.18 (95% CI 4.97, 10.36)]. Other risk factors for MAS included female gender, age ≥65 years, low income, a history of inflammatory bowel disease and a history of MAS. Conclusion This nationwide, population-based study revealed that a history of MAS was not significantly associated with SLE risk. However, the risk of MAS was markedly associated with SLE and a history of MAS.

The purposes of the study were (1) to assess the physical activity (PA) status, muscle strength (MS), and flexibility of survivors of head and neck cancer (HNC) and compare these findings with normative data from national labor fitness measures; (2) to examine the differences among PA subgroups, as categorized using Godin’s scores; and (3) to examine the association between stretching exercises and cervical range of motion (CROM). A cross-sectional study with consecutive sampling was used to recruit HNC survivors from a medical center in Northern Taiwan who had completed either radiation therapy (RT) or multimodality treatments including RT within the current 5 years. The level of PA, daily function, fatigue, quality of life (QOL), MS (handgrip and hip flexor), BMI, and flexibility (CROM and fingertip-to-floor tests) of the participants were assessed. A total of 108 participants completed the assessments from 135 eligible patients (80% response rate). Although 60.2% reported engaging in PA, only 16.7% met WHO guidelines. Compared to subjects in the normative data, the survivors of HNC in this study had poorer handgrip strength, BMI, and CROM, but better forward flexion. The participants who were consistent with WHO PA guidelines reported less fatigue, better right hip flexor MS, and better QOL than those who did not engage in any PA. Lack of sufficient PA and generally poorer fitness were found in study subjects. Longitudinal research to explore changes in fitness and barriers to PA compliance is strongly suggested to better enhance HNC patients’ PA and fitness.

Systemic lupus erythematosus (SLE) is an autoimmune disease that develops mainly in women of reproductive age. We aimed to explore the risk of pregnancy complications in Asian patients with SLE.From January 2005 to December 2014, we conducted a nationwide case-control study, using Taiwan's National Health Insurance Research Database. Obstetric complications and perinatal outcomes in SLE patients were compared with those without SLE.2059 SLE offspring and 8236 age-matched, maternal healthy controls were enrolled. We found increased obstetric and perinatal complications in SLE population compared with healthy controls. SLE patients exhibited increased risk of preeclampsia/eclampsia (8.98% vs.1.98%, odds ratio [OR]: 3.87, 95% confidence interval [95% CI]: 3.08-4.87, p0.0001). Their offspring tended to have lower Apgar scores (7) at both 1 min (10.7% vs. 2.58%, p0.0001) and 5 min (4.25% vs. 1.17%, p0.0001), as well as higher rates of intrauterine growth restriction (IUGR, 9.91% vs. 4.12%, OR: 2.24, 95% CI: 1.85-2.71, p0.0001), preterm birth (23.70% vs 7.56%, OR: 3.00, 95% CI: 2.61-3.45, p0.0001), and stillbirth (4.23% vs. 0.87%, OR: 3.59, 95% CI: 2.54-5.06, p0.0001). The risks of preterm birth and stillbirth were markedly increased in SLE patients with concomitant preeclampsia/eclampsia or IUGR. Preterm birth of SLE patients was 1~4 gestational weeks earlier than that of healthy controls and the peak occurrence of stillbirth in SLE population was at 20~30 gestational weeks.Asian SLE patients exhibited increased risks of maternal complications and adverse birth outcomes. Frequent antenatal visits before 20 gestational weeks are recommended in high-risk SLE patients.

A major obstacle to nanodrugs-mediated cancer therapy is their rapid uptake by the reticuloendothelial system that decreases the systemic exposure of the nanodrugs to tumors and also increases toxicities. Intralipid has been shown to reduce nano-oxaliplatin-mediated toxicity while improving bioavailability. Here, we have found that Intralipid reduces the cytotoxicity of paclitaxel for human monocytic cells, but not for breast, lung, or pancreatic cancer cells. Intralipid also promotes the polarization of macrophages to the anti-cancer M1-like phenotype. Using a xenograft breast cancer mouse model, we have found that Intralipid pre-treatment significantly increases the amount of paclitaxel reaching the tumor and promotes tumor apoptosis. The combination of Intralipid with half the standard clinical dose of Abraxane reduces the tumor growth rate as effectively as the standard clinical dose. Our findings suggest that pre-treatment of Intralipid has the potential to be a powerful agent to enhance the tumor cytotoxic effects of Abraxane and to reduce its off-target toxicities.

Life-threatening electrolyte imbalance is not uncommon in preemies. Differential diagnosis is important for immediate treatment. The syndrome of pseudohypoaldosteronism (PHA) is characterized by increased aldosterone secretion associated with clinical signs of hypoaldosteronism reflecting mineralocorticoid resistance. There are type I, type II, and secondary type of PHA. Most secondary PHA reported in the pediatric population result from urinary infection and obstructive uropathy and extremely rarely from gastrointestinal fluid loss. Seven preemies accepted jejunostomy or ileostomy, and they suffered from high output stoma. Electrolyte imbalance with bodyweight loss or cardiac event was noted. We found a high level of aldosterone and renin and diagnosed them with secondary PHA due to excessive gastrointestinal losses. After stomal reversal, aldosterone and renin level became normalized, and electrolyte was corrected. This study reports the finding of secondary pseudohyperaldosteronism (hyponatremia, hyperkalemia, and metabolic acidosis) in a series of cases with intestinal resection and ostomy of different causes. Early stomal reversal was recommended.

Background: ABCG2 rs2231142 is an important genetic factor that contributes to the development of gout and hyperuricemia (HUA). Epidemiologic studies have demonstrated that lifestyle risk factors of HUA (e.g., alcohol consumption) and genetic predisposition (e.g., ABCG2 gene) together, contribute to enhanced serum uric acid levels. However, the interaction between ABCG2 rs2231142, alcohol consumption, and HUA in the Taiwanese population is still unclear. Therefore, this study investigated whether the risk of HUA is associated with ABCG2 rs2231142 variants and how this is affected by alcohol consumption. Method: study subjects were selected from the participants of the Taiwan Biobank database. Overall, 114,540 participants aged 30 to 70 years were enrolled in this study. The interaction between ABCG2 rs2231142, alcohol consumption, and serum uric acid (sUA) levels was analyzed by multiple logistic regression models. Results: the prevalence of HUA was 32.7% and 4.4 % in the male and female populations, respectively. In the whole study population, the minor T allele of ABCG2 rs2231142 was significantly associated with HUA risk, and the occurrence of HUA was high in TT genotype and TG genotype. The risk of HUA was significantly increased by the combined association of ABCG2 rs2231142 and alcohol consumption for TG/TT genotype compared to the GG genotype (wild-type genotype), especially among women. Conclusion: the ABCG2 rs2231142 is a crucial genetic locus for sUA levels in the Taiwanese population and our findings revealed that alcohol consumption combined with the ABCG2 rs2231142 risk allele contributes to increased HUA risk.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

Simple Summary β-escin, a component of horse chestnut seed extract, was first identified as an inhibitor of ovarian cancer (OvCa) adhesion/invasion in our high-throughput screening program using a three-dimensional organotypic model assembled from primary human cells and extracellular matrix. The goal of the study presented here is to determine if β-escin and structurally-similar compounds have a therapeutic potential against OvCa metastasis. β-escin and cardiac glycosides inhibit ovarian cancer adhesion/invasion to the omental microenvironment in vivo, and β-escin inhibits ovarian cancer metastasis in the prevention and intervention setting. Additionally, β-escin was found to decrease the stemness of ovarian cancer cells, inhibit extracellular matrix production in the tumor microenvironment, and inhibit HIF1α stability in ovarian cancer cells and the tumor microenvironment. This study reveals that the natural compound β-escin has therapeutic potential because of its ability to prevent OvCa dissemination by targeting both cancer and stromal cells in the OvCa tumor microenvironment. Abstract The high mortality of OvCa is caused by the wide dissemination of cancer within the abdominal cavity. OvCa cells metastasize to the peritoneum, which is covered by mesothelial cells, and invade into the underlying stroma, composed of extracellular matrices (ECM) and stromal cells. In a study using a three-dimensional quantitative high-throughput screening platform (3D-qHTS), we found that β-escin, a component of horse chestnut seed extract, inhibited OvCa adhesion/invasion. Here, we determine whether β-escin and structurally similar compounds have a therapeutic potential against OvCa metastasis. Different sources of β-escin and horse chestnut seed extract inhibited OvCa cell adhesion/invasion, both in vitro and in vivo. From a collection of 160 structurally similar compounds to β-escin, we found that cardiac glycosides inhibited OvCa cell adhesion/invasion and proliferation in vitro, and inhibited adhesion/invasion and metastasis in vivo. Mechanistically, β-escin and the cardiac glycosides inhibited ECM production in mesothelial cells and fibroblasts. The oral administration of β-escin inhibited metastasis in both OvCa prevention and intervention mouse models. Specifically, β-escin inhibited ECM production in the omental tumors. Additionally, the production of HIF1α-targeted proteins, lactate dehydrogenase A, and hexokinase 2 in omental tumors was blocked by β-escin. This study reveals that the natural compound β-escin has a therapeutic potential because of its ability to prevent OvCa dissemination by targeting both cancer and stromal cells in the OvCa tumor microenvironment.

Objectives: Genetic variants and obesity are risk factors for hyperuricemia (HUA). Recent genome-wide association studies have identified ABCG2 rs2231142 as one of the most prominent genetic variants for HUA in an East Asian population. Nevertheless, no large-scale studies have demonstrated any interactive effects between this variant and obesity on serum urate level in Asians. This study aimed to determine the interaction of ABCG2 rs2231142 variant and body mass index (BMI) and its effect on risk of HUA in an East Asian population.Methods: The study was conducted using the Taiwan Biobank database, a population-based biomedical research database of patients with Taiwanese Han Chinese ancestry aged 30–70years between September 2014 and May 2017. Detailed physical information on participants were collected by questionnaires and genotyping using Affymetrix TWB 650K SNP chip. The primary outcome was HUA, defined as a serum uric acid level>7.0mg/dl. Odds ratio (OR) of HUA was analyzed using logistic regression models and the effects of interaction between ABCG2 rs2231142 variants and BMI on serum uric acid level were explored.Results: We identified 25,245 subjects, 4,228 (16.75%) of whom had HUA. The prevalence of HUA was 30% in men and 3.8% in women. The risk of HUA was significantly associated with ABCG2 rs2231142 risk T allele, with more HUA in TT genotype (OR: 2.40, 95% CI: 2.11–2.72, ppppABCG2 rs2231142 variant and BMI for TT genotype (OR: 7.42, 95% CI: 2.54–21.7, pppp=0.011) in women compared with the GG genotype in women.Conclusion: The risk of HUA was markedly increased by the interaction of ABCG2 rs2231142 variant and BMI, both in men and in women. Body weight control and reduction in BMI are recommended in high-risk patients with the ABCG2 rs2231142 risk T allele.

Objectives: To investigate factors associated with major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA). Methods: We conducted a nationwide, population-based, case-control study using Taiwan’s National Health Insurance Research Database for 2003–2013. From 2004 to 2012, we identified 108,319 newly diagnosed RA patients without previous MACEs, of whom 7,580 patients (7.0%) developed MACEs during follow-up. From these incident RA patients, we included 5,994 MACE cases and 1:4 matched 23,976 non-MACE controls for analysis. The associations of MACEs with comorbidities and use of anti-rheumatic medications within 1 year before the index date were examined using conditional logistic regression analyses. Results: Using multivariable conditional logistic regression analysis, the risk of MACE in RA patients was associated with use of golimumab [odd’s ratio (OR), 0.09; 95% confidence interval (CI), 0.01-0.67], abatacept (OR, 0.13; 95% CI, 0.02–0.93), hydroxychloroquine (OR, 0.90; 95% CI, 0.82-0.99), methotrexate (OR, 0.72; 95% CI, 0.64–0.81), cyclosporin (OR, 1.43; 95% CI, 1.07–1.91), nonsteroidal anti-inflammation drugs (NSAIDs) (OR, 1.36; 95% CI, 1.27–1.46), antiplatelet agent (OR, 2.47; 95% CI, 2.31-2.63), hypertension (without anti-hypertensive agents: OR, 1.04; 95% CI, 0.96-1.12; with anti-hypertensive agents: OR, 1.47; 95% CI, 1.36-1.59), diabetes (OR, 1.27; 95% CI, 1.18-1.37), hyperlipidemia without lipid-lowering agents (OR, 1.09; 95% CI, 1.01-1.17), ischemic heart disease (OR, 1.20; 95% CI, 1.10-1.31), and chronic obstructive pulmonary disease (COPD) (OR, 1.12; 95% CI, 1.03-1.23) in the parsimonious model. The risk of MACE in RA patients also increased markedly in participants younger than 65 years with some comorbidities. Conclusions: This population-based case-control study revealed that the use of golimumab, abatacept, hydroxychloroquine, and methotrexate were associated with a decreased risk of MACE development in newly diagnosed RA patients, while the use of cyclosporin, NSAIDs, and antiplatelet agents, and comorbidities, including hypertension, diabetes, hyperlipidemia without lipid-lowering agent therapy, ischemic heart disease, and COPD, were associated with an increased risk of MACE development in RA patients.

The risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after glucocorticoid (GC) pulse therapy remains unclear. Aims: Our study aimed to examine the safety of GC pulse therapy in HBsAg-negative, anti-HBc-positive rheumatic patients. Methods: Medical records of HBsAg-negative, anti-HBc-positive patients receiving GC pulse therapy to treat rheumatic diseases were reviewed. The primary outcome was HBV-associated hepatitis occurring within the first year after GC pulse therapy, the secondary outcome was HBsAg seroreversion occurring during the follow-up period. Results: We identified 5222 HBsAg-negative, anti-HBc-positive patients with rheumatic diseases who had attended Taichung Veterans General Hospital from October 2006 to December 2018. A total of 689 patients had received GC pulse therapy, with 424 patients being analyzed. Hepatitis was noted in 28 patients (6.6%) within the first year after GC pulse therapy, but none had been diagnosed as HBV-associated hepatitis. Three patients (0.7%) later developed HBsAg seroreversion, with a median interval of 97 months from the first episode of GC pulse therapy. These cases concurrently had maintained high dose oral prednisolone (≥20 mg prednisolone daily for over 4 weeks). Conclusions: Amongst the HBsAg-negative, anti-HBc-positive rheumatic patients treated with GC pulse therapy, the risk of HBV-associated hepatitis within the first year was low. HBsAg seroreversion may have developed in the later stage, but only in those patients who had maintained high-dose oral steroid.

Objective: To examine the difference in levels of fear of cancer progression (FoP), anxiety, depression between presence/absence of the target-adverse events (AEs); and to examine the differences in incidence rate of AEs and FoP, anxiety, and depression among three generations of EGFR-TKIs therapy (first, gefitinib and erlotinib [G1]; second, afatinib [G2]; third, osimertinib [G3]) in non-small-cell lung cancer (NSCLC) patients.Methods: A cross-sectional study design. NSCLC patients (n=128) were recruited from a medical center in Taiwan. A set of structured questionnaires assessing AEs, FoP, anxiety and depression. Results: Parts of AEs, such as photosensitivity, paronychia, and alopecia, exhibited significantly higher levels of FoP, anxiety, and depression. Less patients experienced AEs in the G3 group than those in the G1 or G2 group but still reported experiencing itching, dry skin with grade 3 severity. The incidence rates of mouth/throat sores, and cheilosis/cheilitis in the G2 group was significantly higher than those in the G1 or G3 group. The incidence rate of FoP, anxiety and depression were 13.8-26.3%, 23.8-40.4% and 16.7-42.1%, respectively.Conclusions: The priorities of care among three generations of EGFR-TKIs in patients with NSCLC were established. FoP, anxiety and depression were present among different targeted therapies and require further attention.

Invasive interventions have been conducted in preterm infants with significant patent ductus arteriosus (PDA) when medical treatment has failed, and methods of invasive intervention have been reported. Surgical ligation via lateral thoracotomy has been a well-established procedure for decades. Recently, transcatheter occlusion has been safely and feasibly applied to the premature population. However, little research has been conducted on the benefits of transcatheter occlusion in very-low-birth-weight (VLBW) infants compared to surgical ligation. This study compared transcatheter and surgical techniques in VLBW infants in terms of short-term respiratory outcomes. The medical records of 401 VLBW infants admitted to a tertiary hospital between September 2014 and January 2019 were retrospectively reviewed. Patients who were diagnosed with a congenital anomaly, a chromosomal anomaly, or congenital heart disease, except for an inter-atrial shunt, were excluded. The perinatal conditions, neonatal morbidities, periprocedural vital signs, and respiratory support trajectories were compared between the transcatheter-treated and surgically ligated group. A total of 31 eligible VLBW infants received invasive intervention: 14 were treated with transcatheter occlusion (Group A), and 17 infants were treated with surgical ligation (Group B). Respiratory outcomes were not statistically significant between the two groups, despite Group A showing a trend toward early improvement in post-intervention respiratory trajectory. In this small case study, a different trend in post-intervention respiratory trajectories was observed. Future research with larger case numbers should be conducted to address our preliminary observations in more detail.

Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome-wide association study was performed to identify single-nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT-associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti-HCV seropositive patients was used for genome-wide SNP array to examine the associations with baseline ALT levels. SNPs 15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow-up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p 15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11-1.78) and 1.86 (1.34-2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90-4.89) for AC and 2.64 (1.13-6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals.

Primary congenital hypothyroidism is a disease associated with low serum thyroxine and elevated thyroid-stimulating hormone (TSH) levels. The processes of screening and treating congenital hypothyroidism, in order to prevent neurodevelopmental impairment (NDI) in newborns, have been well investigated. Unlike term infants, very preterm infants (VPIs) may experience low thyroxine with normal TSH levels (&lt, 10.0 μIU/mL) during long-stay hospitalization. In the current literature, thyroxine treatment has been evaluated only for TSH-elevated VPIs. However, the long-term impact of low thyroxine levels in certain VPIs with normal TSH levels deserves more research. Since July 2007, VPIs of this study unit received screenings at 1 month postnatal age (PNA) for serum TSH levels and total thyroxine (TT4), in addition to two national TSH screenings scheduled at 3–5 days PNA and at term equivalent age. This study aimed to establish the correlation between postnatal 1-month-old TT4 concentration and long-term NDI at 24 months corrected age among VPIs with serial normal TSH levels. VPIs born in August 2007–July 2016 were enrolled. Perinatal demography, hospitalization morbidities, and thyroid function profiles were analyzed, and we excluded those with congenital anomalies, brain injuries, elevated TSH levels, or a history of thyroxine treatments. In total, 334 VPIs were analyzed and 302 (90.4%) VPIs were followed-up. The postnatal TT4 concentration was not associated with NDI after multivariate adjustment (odd ratios 1.131, 95% confidence interval 0.969–1.32). To attribute the NDI of TSH-normal VPIs to a single postnatal TT4 concentration measurement may require more research.

MicroRNA-27 is a critical non-coding metabolic gene that is often aberrantly overexpressed in non-alcoholic fatty livers (NAFLD). However, the pathogenic role of miR-27 in NAFLD remains unknown. In this study, we attempted to identify the mechanism by which miR-27 was regulated in the context of insulin resistance, a predisposed metabolic disorder in NAFLD. Our data from cell culture and animal studies showed that insulin, CREB, and Hippo signalings coordinately regulated miR-27. First, miR-27 was upregulated in palmitate-treated cells and high fat diet-fed mouse livers, which exhibited insulin resistance and CREB overexpression. Second, miR-27 peaked in the mouse liver at the post-absorptive phase when CREB activity was increased. Also, miR-27 was increased rapidly in cell lines when CREB was deactivated by insulin treatment. Third, miR-27 was decreased in cultured cells when CREB was downregulated by siRNA or metformin treatment. In contrast, Forskolin-mediated activation of CREB promoted miR-27 expression. Fourth, Hippo signaling repressed miR-27 in a CREB-independent manner: miR-27 was reduced in cells at full confluence but was inhibited in cells transfected with siRNA against Lats2 and Nf2, which were two positive regulators of Hippo signaling. Lastly, bioinformatics and luciferase assay showed that miR-27 inhibited Akt phosphorylation by targeting Pdpk1 and Pik3r1. Overexpression of miR-27 impaired Akt phosphorylation in cell lines and primary mouse hepatocytes upon insulin stimulation. In conclusion, our data suggest that insulin, CREB, and Hippo signalings contribute to aberrant miR-27 overexpression and eventually lead to insulin resistance in NAFLD.

Introduction Fecal immunochemical testing (FIT) is the most commonly used colorectal cancer (CRC) screening tool worldwide and accounts for 10% of all CRC screening in the United States. Potential vulnerabilities for patients enrolled to facilities within the military health system have recently come to light requiring reassessment of best practices. We studied the impact of a process improvement initiative designed to improve the safety and quality of care for patients after a positive screening FIT given previously published reports of poor organization performance. Methods During a time of increased utilization of nonendoscopic means of screening, we assessed rates of colonoscopy completion and time to colonoscopy after positive FIT after a multi-faceted process improvement initiative was implemented, compared against an institutional control period. The interventions included mandatory indication labeling at the time of order entry, as well as utilization of subspecialty nurse navigators to facilitate rapid follow-up even the absence of a referral from primary care. Results Preintervention, 34.8% of patients did not have appropriate follow-up of a positive FIT. Those that did had a variable and prolonged wait time of 140.1 ± 115.9 days. Postintervention, a standardized order mandating test indication labeling allowed for proactive gastroenterology involvement. Colonoscopy follow-up rate increased to 91.9% with an average interval of 21.9 ± 12.3 days. Conclusion The addition of indication labels and patient navigation after positive screening FIT was associated with 57.1% absolute increase in timely diagnostic colonoscopy. Similar highly reliable systems-based solutions should be adopted for CRC screening, and further implementation for other preventative screening interventions should be pursued.

No standard treatment for Bacille Calmette–Guérin (BCG)-associated osteomyelitis, a rare but serious complication of the BCG vaccine, has been established. This study explored the short- and long-term outcomes of surgical intervention for BCG-associated osteomyelitis. Four patients with BCG osteomyelitis aged 9–21 months when diagnosed and treated at the Department of Orthopedics, Kaohsiung Veterans General Hospital, Taiwan, between January 2001 and April 2019 were analysed. Radiography revealed osteolytic lesions of the involved sites. Magnetic resonance imaging revealed physeal involvement in three patients. Debridement was performed for all four patients. One patient then underwent additional arthroscopy because of suspect intra-articular involvement. Specimens obtained intraoperatively were sent for pathology, culture, and to the national reference mycobacterial laboratory for BCG detection using polymerase chain reaction. All four patients had positive results for Mycobacterium bovis and satisfactory short-term results. Functional monitoring using QuickDASH or the Lower Extremity Functional Scale revealed excellent long-term outcomes despite tiny limb length discrepancy observed during follow-up in two patients. Prompt diagnosis plus proper intervention is required to prevent further major complications of BCG osteomyelitis. Minimally invasive debridement led to positive clinical outcomes and is therefore recommended.

Skeletal muscle, a highly metabolic tissue, is particularly vulnerable to increased levels of saturated free fatty acids (FFAs). The role of autophagy in saturated FFAs-induced cellular senescence and insulin resistance in skeletal muscle remains unclear. Therefore, the present study was aimed to explore autophagic flux in cellular senescence and insulin resistance induced by palmitate in muscle cells, and whether resveratrol limited these responses. Our results showed that palmitate induced cellular senescence in both myoblasts and myotubes. In addition, palmitate delayed differentiation in myoblasts and inhibited expression of insulin-stimulated p-AKTSer473 in myotubes. The accumulations of autophagosome assessed by tandem fluorescent-tagged LC3 demonstrated that autophagic flux was impaired in both palmitate-treated myoblasts and myotubes. Resveratrol protected muscle cells from palmitate-induced cellular senescence, apoptosis during differentiation, and insulin resistance via ameliorating autophagic flux. The direct influence of autophagic flux on development of cellular senescence and insulin resistance was confirmed by blockage of autophagic flux with chloroquine. In conclusion, impairment of autophagic flux is crucial for palmitate-induced cellular senescence and insulin resistance in muscle cells. Restoring autophagic flux by resveratrol could be a promising approach to prevent cellular senescence and ameliorate insulin resistance in muscle. Keywords: Autophagic flux, Resveratrol, Cellular senescence, Insulin resistance

Background/purpose The purposes of this three-phase study were to: (1) translate and evaluate the burden, content, and face validity of the Chinese version of the University of Washington Quality of Life Scale, version 4 (UWQOL-v4-C); and (2) examine the psychometric properties of the UWQOL-v4-C in oral cancer and laryngeal cancer patients in Taiwan. Methods This instrument translation and validation study was part of a major research project. The first phase of this study developed and validated the content of the UWQOL-v4-C. The second phase sought to validate the internal consistency, reliability, and construct and discriminant validity in two major groups of head and neck cancer (HNC) patients: oral cavity cancers (n = 109) and laryngeal cancer (n = 102). Construct validity was measured using theoretically supported correlations between the UWQOL and related constructs. Discriminant validity was also assessed. In the third phase, test–retest reliability of UWQOL-v4-C was examined through the 1-week interval in another group of HNC patients (n = 50). Results The translated UWQOL-v4-C demonstrated satisfactory face validity, content validity, and minimal patient burden. Additionally, the UWQOL-v4-C showed excellent construct validity in patient testing, supported by significant correlations between the UWQOL-v4-C and hypothesized constructs, including generic measures of QOL and performance status. The developed scale correlated inversely with symptom severity and psychological distress. Discriminant validity was seen in patients with different cancer diagnoses, stages, and treatments. Finally, excellent stability was supported by a 1-week test–retest reliability of 0.88. Conclusion The UWQOL-v4-C was a brief, low-burden, and valid instrument to measure the QOL in Chinese-speaking HNC patients in Taiwan.

The tumor microenvironment (TME) is a key determinant of metastatic efficiency. We performed a quantitative high-throughput screen (qHTS) of diverse medicinal chemistry tractable scaffolds (44,420 compounds) and pharmacologically active small molecules (386 compounds) using a layered organotypic, robust assay representing the ovarian cancer metastatic TME. This 3D model contains primary human mesothelial cells, fibroblasts, and extracellular matrix, to which fluorescently labeled ovarian cancer cells are added. Initially, 100 compounds inhibiting ovarian cancer adhesion/invasion to the 3D model in a dose-dependent manner were identified. Of those, eight compounds were confirmed active in five high-grade serous ovarian cancer cell lines and were further validated in secondary in vitro and in vivo biological assays. Two tyrosine kinase inhibitors, PP-121 and milciclib, and a previously unreported compound, NCGC00117362, were selected because they had potency at 1 μmol/L in vitro. Specifically, NCGC00117362 and PP-121 inhibited ovarian cancer adhesion, invasion, and proliferation, whereas milciclib inhibited ovarian cancer invasion and proliferation. Using in situ kinase profiling and immunoblotting, we found that milciclib targeted Cdk2 and Cdk6, and PP-121 targeted mTOR. In vivo, all three compounds prevented ovarian cancer adhesion/invasion and metastasis, prolonged survival, and reduced omental tumor growth in an intervention study. To evaluate the clinical potential of NCGC00117362, structure–activity relationship studies were performed. Four close analogues of NCGC00117362 efficiently inhibited cancer aggressiveness in vitro and metastasis in vivo. Collectively, these data show that a complex 3D culture of the TME is effective in qHTS. The three compounds identified have promise as therapeutics for prevention and treatment of ovarian cancer metastasis.

Objective Head and neck cancer (HNC) patients suffer from symptoms and fear of recurrence (FoR), which both affect their quality of life (QoL). Based on a self-regulation model, the purpose of the study was to examine patients' FoR as a mediator of the relation between symptoms and QoL, and to identify which symptoms may trigger FoR. Methods A cross-sectional study was conducted, using convenience sampling. Structured questionnaires were used to collect data at a medical centre in Northern Taiwan. The analytic methods included descriptive statistics, structural equation modelling and linear regression. Results A total of 103 participants were recruited. Patients experienced a medium level of symptom severity and QoL but a moderate to high level of FoR. Symptom severity, FoR and QoL were significantly correlated. FoR was a significant partial mediator between symptom severity and QoL. The significant factors of the overall FoR and the subscale of health worry were "pain in general" and "pain in the mouth, throat or neck." "Pain in general" was a significant factor for the subscale of cancer worry. Conclusions This theory-driven study supports a mediation model of FoR among HNC patients and provides a more comprehensive understanding of the antecedents and consequences of FoR.

Oncology outpatient care centers generally subjugate patients' psychosocial needs to their physical care requirements. Consequently, the patients' self-management (SM) ability and utilization of social resources are essential in regulating their psychological distress (anxiety and depression). The study aims were (1) to examine the prevalence and severity of psychological distress in female cancer patients in outpatient settings in Taiwan and (2) to identify the major factors of psychological distress. Female cancer patients were recruited from oncology outpatient settings in Taiwan. Patients completed the questionnaires of anxiety, depression, social support, and utilization of social resources, and SM ability. In total, 116 patients were included. A total of 17.2% and 21.6% of the patients were at risk of anxiety and depression, respectively. Patients' mean anxiety and depression scores were 4.2 (SD = 4.1) and 4.1 (SD = 4.0), respectively. The patients' physical function, attendance of social support groups, degree of social support, and SM ability had a significant effect on their anxiety and depression. Patients' anxiety was intensified by the presence of comorbidity. Health professionals in oncology outpatient care centers should assess the patients' physical function, comorbidity, SM ability, and social support/engagement in order to reduce their psychological distress and devise appropriate follow-up interventions.

This study aimed to investigate the associations between Walk Score&reg, and lifestyle behaviors and health outcomes in older Taiwanese adults. A nationwide survey was conducted through telephone-based interviews with older adults (65 years and older) in Taiwan. Data on Walk Score&reg, lifestyle behaviors (physical activity, sedentary behavior, healthy eating behavior, alcohol use, and smoking status), health outcomes (overweight/obesity, hypertension, type 2 diabetes, and cardiovascular disease), and personal characteristics were obtained from 1052 respondents. A binary logistic regression adjusting for potential confounders was employed. None of the Walk Score&reg, categories were related to the recommended levels of total physical activity. The categories &ldquo, very walkable&rdquo, and &ldquo, walker&rsquo, s paradise&rdquo, were positively related to total sedentary time and TV viewing among older adults. No significant associations were found between Walk Score&reg, and other lifestyle health behaviors or health outcomes. While Walk Score&reg, was not associated with recommended levels of physical activity, it was positively related to prolonged sedentary time in the context of a non-Western country. The different associations between the walk score and health lifestyle behaviors and health outcomes in different contexts should be noted.

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR+ activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.

cope An elevated intracellular lipid contents resulted from lipid oversupply links obesity to insulin resistance. Flavanol-rich lychee fruit extract, oligonol, exhibited anti-obesity property in vitro and in vivo; however, the effects of oligonol on peripheral lipid metabolism and insulin sensitivity have not been fully investigated. We hypothesized that oligonol alleviated insulin resistance via decreasing intracellular lipid contents in peripheral tissues. Methods and results Dietary oligonol supplementation (20 or 200 mg/kg bw) reduced glucose and insulin levels, improved oral glucose tolerance, and suppressed inflammatory markers, MCP-1 and IL-6, in High-Fat diet (HFD) induced obese mice. Marked decreases in subcutaneous and visceral fat area, adipocyte size, and adipocyte released hormones including leptin and resistin by high-dose oligonol treatment were associated with downregulation of PPARγ gene expression. Significantly reduced intrahepatocellular lipid contents and hepatic triglyceride levels by oligonol (both doses) were associated with downregulation of mTOR/SREBP-1-mediated de novo lipogenesis. In skeletal muscle, oligonol enhanced Sirtuin1 protein expression and AMPKα activation, consequently resulted in reductions of intramuscular lipid contents and triglyceride levels and restoration of IRS-1 and AS160 phosphorylation. Conclusion Oligonol reduced intracellular lipid contents in liver and skeletal muscle and suppressed inflammatory markers, thereby alleviating HFD-induced insulin resistance.

Topical steroids are first-line treatment agents for eosinophilic esophagitis; however, some studies have demonstrated modest efficacy in inducing histologic remission.The aim of this study was to determine response to two topical steroids (fluticasone and budesonide), compare their efficacy, and examine patient characteristics which could predict non-response to topical steroids.We performed a retrospective review of an established EoE registry. Inclusion criteria were patients1 year of age who were diagnosed with EoE as defined by the most recent consensus guidelines. All patients were treated with an 8-week course of either swallowed fluticasone or viscous budesonide. Responders were defined as achieving15 eosinophils per high-power field (eos/hpf) in both proximal and distal esophageal biopsies. Demographic, clinical, endoscopic, and histologic features were examined.The study cohort included 75 EoE patients with a median age of 33 years (range 2-64 years), 71 % adults, 84 % male, and 76 % Caucasian. Overall histologic response rate to topical steroids was 51 %, while clinical response was 71 %. There was no significant differences in histologic response to treatment between children and adults (68 vs. 44 %, p = 0.111). There was no significant difference in response between males and females (47 vs. 73 %, p = 0.191) and between the two types of steroids (48 vs. 56 %, p = 0.632). Responders and non-responders were similar in clinical presentation and baseline endoscopic findings. Following treatment, responders had significantly less peak proximal (4.0 ± 4.4 vs. 46 ± 53, p 0.001) and distal eosinophil counts (3.5 ± 3.8 vs. 60 ± 47, p 0.001) compared to non-responders. There were no predictors of response to steroids identified.Histologic response to treatment was observed in approximately half the cohort, while more than two-thirds experienced clinical response to topical steroids. Response was similar between fluticasone and budesonide. Given the lack of differences in clinical presentation or endoscopic features, predictors of non-response were not seen.

Avicennia marina is the most abundant and common mangrove species and has been used as a traditional medicine for skin diseases, rheumatism, ulcers, and smallpox. However, its anticancer activities and polyphenol contents remain poorly characterized. Thus, here we investigated anticancer activities of secondary A. marina metabolites that were purified by sequential soxhlet extraction in water, ethanol, methanol, and ethyl acetate (EtOAc). Experiments were performed in three human breast cancer cell lines (AU565, MDA-MB-231, and BT483), two human liver cancer cell lines (HepG2 and Huh7), and one normal cell line (NIH3T3). The chemotherapeutic potential of A. marina extracts was evaluated in a xenograft mouse model. The present data show that EtOAc extracts of A. marina leaves have the highest phenolic and flavonoid contents and anticancer activities and, following column chromatography, the EtOAc fractions F2-5, F3-2-9, and F3-2-10 showed higher cytotoxic effects than the other fractions. 1H-NMR and 13C-NMR profiles indicated that the F3-2-10 fraction contained avicennones D and E. EtOAc extracts of A. marina leaves also suppressed xenograft MDA-MB-231 tumor growth in nude mice, suggesting that EtOAc extracts of A. marina leaves may provide a useful treatment for breast cancer.

Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx. Although a combination of radiotherapy with chemotherapy is effective for therapy, relapse and metastasis after remission remain major causes of mortality. Epstein-Barr virus (EBV) is believed to be one of causes of NPC development. We demonstrated previously that EBV reactivation is important for the carcinogenesis of NPC. We sought, therefore, to determine whether EBV reactivation can be a target for retardation of relapse of NPC. After screening, we found luteolin is able to inhibit EBV reactivation. It inhibited EBV lytic protein expression and repressed the promoter activities of two major immediate-early genes, Zta and Rta. Furthermore, luteolin was shown to reduce genomic instability induced by recurrent EBV reactivation in NPC cells. EBV reactivation-induced NPC cell proliferation and migration, as well as matrigel invasiveness, were also repressed by luteolin treatment. Tumorigenicity in mice, induced by EBV reactivation, was decreased profoundly following luteolin administration. Together, these results suggest that inhibition of EBV reactivation is a novel approach to prevent the relapse of NPC.

Gamma knife treatment outcome of large pituitary tumors which are only partially irradiated secondary to immediate proximity to critical structures such as the optic apparatus have not been rigorously studied.From July 2003 to December 2013, there were 41 cases of recurrent or residual nonfunctioning pituitary macroadenoma partially treated with gamma knife radiosurgery (GKRS) because the adenoma obscured part of the optic apparatus on planning SRS MR imaging.The follow up period after GKRS was 92.3 ± 5.6 months. The percentage of tumor coverage with the full dose was 88.5 ± 0.7%. Five of 43 (11.6%) patients experienced a transient visional decrease and one patient experienced a permanent visual field defect. During the follow up, two patients underwent transphenoidal surgery and one patient had a craniotomy due to tumor progression. Seven patients (16.2%) developed cortisol and thyroxine deficiencies. In multiple variant analyses, transient visual decline was correlated to the tumor volume ( 3.5 cc), percentage of tumor coverage ( 90%), the distance from the optic apparatus to the pituitary stalk ( 15 mm) and percentage of tumor above the orbital apex (65%).In the limited case of this cohort, we found that partially treated pituitary nonfunctioning macroadenoma yielded a high tumor control rate. However, visual decline as a result of tumor progression or radiation effect can occur in a minority of patients. The radiosurgical technique warrants further study to better define the long-term risk to benefit profile for its use in complex pituitary macroadenoma obscuring part of the optic apparatus.

Background: Continuous glucose monitoring (CGM) uses subcutaneous sensors and records the average interstitial sensor current every 5 min in the recorder; data are subsequently exported to a computer 4 to 7 days later when calibration with self-measured blood glucose is made retrospectively. How middle-aged and older patients perceive the added technology intervention is not clear. Objective: The study aimed to understand the factors associated with the adoption of new technology in diabetes care, to understand the feelings and behaviors while using it, and to determine the changes in attitudes and behavior after completing the use of the new technology at the 3-month follow-up. Methods: Middle-aged and older type 2 diabetes patients who had received professional continuous glucose monitoring (iPro 2 [Medtronic]) were invited for semistructured in-depth interviews on the day of the CGM sensor removal and at 3 months after CGM-based counseling. A phenomenography approach was used to analyze the interview data. Results: A total of 20 type 2 diabetes patients (aged 53 to 72 years, 13 males and 7 females, 4 to 40 years duration of diabetes, mean glycated hemoglobin 8.54% [SD 0.71%]) completed 2 sections of semistructured in-depth interviews. Physician guidance and participant motivation toward problem solving were found to be factors associated with adoption of the device. Participants indicated that technology can be a reminder, a supervisor, and a visualizer of blood glucose, all of which are helpful for disease management. However, CGM is somewhat inconvenient, and some participants also reported that the provision of this new technology might be a hint of disease progression. There was a higher percentage of women compared with men who reported that CGM can be a reminder or a supervisor to help them with diet control. Conclusions: Physician guidance and participants’ degree of motivation are keys to adopting new technology in the case of middle-aged and older adults. Although the CGM sensor may cause inconvenience to patients on their limited body movement when wearing the device, it is helpful for diet control and is an effective behavioral modification tool that offers support, especially in the case of women.

Background Gamma Knife radiosurgery (GKRS) is an important part of the neurosurgical armamentarium in the treatment of acoustic neuromas. However, the treatment outcome related to the morphology of the tumor has not been rigorously studied. In this cohort, we evaluated the morphological features of the tumor in the tumor response and neurological outcomes after GKRS. Material and methods From July 2003 to December 2008, there were 93 cases of acoustic neuromas treated upfront with GKRS with 64 cases with serviceable hearing and 29 cases without serviceable hearing to fulfill the margin dose of 12Gy with at least follow up 5 years. Results The duration of symptom before GKRS in serviceable /no serviceable hearing was 7.9 ± 1.2 and 15.3 ± 3.1 months (p

Summary Background Combined with 24-h pH monitoring, the use of impedance is the most sensitive method available for detecting oesophageal reflux. Normal values for impedance have been previously established in healthy controls studied on and off proton pump inhibitors (PPI). Aims To determine the effects of PPIs on the total number of reflux episodes in the distal oesophagus measured by impedance in patients with and without gastro-oesophageal reflux disease (GERD). Methods In this prospective randomised double-blinded placebo controlled crossover study, all patients underwent two 24-h pH with impedance studies at least 2 weeks apart. Based on a randomisation scheme, patients received either 40 mg of esomeprazole twice daily for 1 week or identical capsule placebo for 1 week, then all patients were crossed over to the other treatment arm. GERD was defined by the validated Johnson–DeMeester score. Reflux by impedance was defined as a 50% decrease from baseline in retrograde movement of liquid between two impedance sites. Results Sixty-three patients were enrolled and 41 patients completed the study [mean age 52 ± 12 years, 42% (17/41) men, 56% (23/41) Caucasian and 34% (14/41) African American]. Overall, there was no significant decrease in the total number of distal impedance episodes with esomeprazole compared with placebo (mean change 6.1 ± 22, P = 0.100). When analysed separately by GERD status, among GERD-positive patients, there was a significant decrease in distal impedance episodes while on esomeprazole compared with placebo (mean change −16 ± 22, P = 0.023), but not in GERD-negative patients (mean change −0.35 ± 20, P = 0.872). Conclusion Esomeprazole decreases significantly the number of reflux episodes detected by impedance, but only in patients with GERD.

BACKGROUND The diagnosis and management of eosinophilic esophagitis (EoE) often requires multiple endoscopies. Serum biomarkers can be elevated in EoE patients, but their clinical utility in diagnosis and assessing response to treatment is not well established. GOALS To evaluate serum biomarkers in EoE subjects compared with controls and assess longitudinally in response to treatment. STUDY We conducted a prospective cohort study of children and adults undergoing esophagogastroduodenoscopy for suspected EoE. After completing an 8-week course of proton-pump inhibitor therapy, esophageal mucosal biopsies were obtained, as well as, serum analysis of absolute eosinophil count (AEC), eotaxin-3, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and interleukin-5. Subjects with normal endoscopic and histologic findings constituted controls. Those meeting criteria for EoE underwent repeat esophagogastroduodenoscopy and biomarker measurements following treatment with topical steroids for 8 weeks. RESULTS Median levels of AEC (263.50 vs. 102 cu/mm, P

Epstein-Barr virus (EBV) has been associated with several human malignancies including nasopharyngeal carcinoma (NPC). Reactivation of latent EBV has been considered to contribute to the carcinogenesis of NPC. Blocking the EBV lytic cycle has been shown effective in the treatment of EBV-associated diseases. We have searched for natural dietary compounds inhibiting EBV reactivation in NPC cells. Among them, sulforaphane (SFN) was found to be effective in the inhibition of EBV reactivation in latent EBV-positive NPC cells, NA and HA. SFN is a histone deacetylase (HDAC) inhibitor and has been recognized as an antioxidant and antitumor compound for chemoprevention. However, its antiviral effect is less well elucidated. In this study, after determination of the cytotoxicity of SFN on various epithelial cells, we showed that SFN treatment inhibits EBV reactivation, rather than induction, by detection of EBV lytic gene expression in EBV-positive NPC cells. We also determined that the number of cells supporting the EBV lytic cycle is decreased using immunofluorescence and flow cytometric analysis. Moreover, we have found that this inhibitory effect decreases virus production. To elucidate the inhibitory mechanism of SFN on the EBV lytic cycle, luciferase reporter assays were carried out on the Zta and Rta promoters. The results show that SFN inhibits transactivation activity of the EBV immediate-early gene Rta but not Zta. Together, our results suggest that SFN has the capability to inhibit EBV lytic cycle and the potential to be taken as a dietary compound for prevention of EBV reactivation.

The lytic reactivation of Epstein-Barr virus (EBV) has been reported to be strongly associated with several human diseases, including nasopharyngeal carcinoma (NPC). Inhibition of the EBV lytic cycle has been shown to be of great benefit in the treatment of EBV-associated diseases. The administration of dietary compounds is safer and more convenient than other approaches to preventing EBV reactivation. We screened several dietary compounds for their ability to inhibit EBV reactivation in NPC cells. Among them, the flavonoid luteolin showed significant inhibition of EBV reactivation. Luteolin inhibited protein expression from EBV lytic genes in EBV-positive epithelial and B cell lines. It also reduced the numbers of EBV-reactivating cells detected by immunofluorescence analysis and reduced the production of virion. Furthermore, luteolin reduced the activities of the promoters of the immediate-early genes Zta (Zp) and Rta (Rp) and also inhibited Sp1-luc activity, suggesting that disruption of Sp1 binding is involved in the inhibitory mechanism. CHIP analysis revealed that luteolin suppressed the activities of Zp and Rp by deregulating Sp1 binding. Taken together, luteolin inhibits EBV reactivation by repressing the promoter activities of Zp and Rp, suggesting luteolin is a potential dietary compound for prevention of virus infection.

One-hundred and thirty confirmed cases of severe acute respiratory syndrome (SARS) were recruited to evaluate their anti-SARS-coronavirus (CoV) antibody status and human leukocyte antigen (HLA) types in September 2006, 3 y after the SARS outbreaks in Taiwan. Western blot assay showed that 6.9% of participants still had anti-spike and anti-nucleocapside antibodies. A case-control study of the association of HLA with SARS revealed that the HLA-Cw1502 and DR0301 alleles conferred resistance against SARS infection (p

Previously, we reported that there was an outbreak of human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The objectives of the present study were to conduct a molecular epidemiological analysis and to characterize the full-length genome of the Taiwanese CRF07_BC.Three hundred and fifty-eight patients with HIV-1/AIDS from hospitals and 133 HIV-1-infected inmates from detention centers were recruited. DNA sequencing and phylogenetic analysis were conducted to determine subtypes and evolutionary relationships. Recombination breakpoints of 2 full-length CRF07_BC strains were elucidated using a bootscanning method.Of 206 HIV-1-infected patients who received a diagnosis in 2004, 44.7% were infected with subtype B, 53.4% with CRF07_BC, and 1.5% with CRF01_AE. Ninety-eight percent (109/111) of IDUs were infected with CRF07_BC. Deletions of 7-11 amino acids in both p6(gag) and p6(pol) proteins were noted among the Taiwanese CRF07_BC strains. The CRF_07BC strains belonged to 2 phylogenetic clusters, and the first cluster contained only CRF07_BC strains from the southern part of Taiwan.The Taiwanese CRF07_BC strains had 97% full-length sequence homology with the prototype from mainland China. CRF07_BC was first introduced into the southern region in 2002 and then spread to other regions in Taiwan in 2004.

The purpose of this study was to review the correlation between the imaging studies and the histological findings in the diagnosis of this disease. We retrospectively reviewed 21 lesions in 20 patients (median age, 23.7 years old) who had been diagnosed with cavernous haemangiomas (n=11), capillary (n=6), and mixed (n=3) types. The imaging studies were obtained with plain film radiography (n=20), Tc-99 m bone scans (n=5), angiography (n=7) and magnetic resonance imaging (MRI; n=20). All the patients underwent marginal to wide excision. Based on the imaging studies, the rate of accurate prediction of intramuscular haemangioma using MRI in our study was 90%. Using the preoperative imaging studies and surgical excisions, only one (5%) local recurrence happened 2 years after marginal excision. The remaining patients were free of disease. For the avoidance of recurrence, wide excision is necessary with the help of the imaging studies, which can provide more specific information, making possible the preoperative identification of characteristic features of the tumuor.

The purpose of this study was to determine the relationships of communication dysfunction, body image, and amount of speaking in patients who were treated for head and neck cancers (HNCs). This was a cross-sectional study of postoperative HNC patients at the otolaryngology outpatient departments of two leading medical centers in northern Taiwan. Data were collected using questionnaires to assess perceived communication dysfunction, body image, symptom severity, and amount of speaking after treatment. A total of 130 HNC patients were included in the analysis, and 70.8 % of patients reported speaking less after surgery as compared to the period before having HNC surgery. Overall, patients perceived a moderate level of communication dysfunction. Those with higher distress over their body image, higher symptom severity, and with hypopharyngeal and laryngeal cancer reported speaking less. Patients with advanced stage cancer and a tumor in a facial area and those that received reconstructive surgery were more likely to have a negative body image. Dissatisfaction with body image, greater symptom severity, and hypopharyngeal and laryngeal cancer are predictive of the amount HNC patients speak, as compared with the amount they spoke before having HNC. Clinicians should be aware of and systematically assess communication problems of HNC patients to promote their social function. Further research on interventions that facilitate the development of a positive body image and communication is strongly suggested.

Distinctively higher plasma G72 protein levels in patients with schizophrenia than in healthy individuals

Background: In 2004, HIV-1 infection among Taiwanese injection drug users (IDUs) started to surge. In 2007, a resurgence of HIV-1 epidemic among men having sex with men (MSM) occurred. We conducted a molecular epidemiological study of HIV-1 among different risk groups in Taiwan from 2005 to 2008. Methods: In total 1133 HIV-1-infected adults including 576 IDUs, 464 MSM, and 93 heterosexuals were recruited. HIV-1 subtypes were determined using nested multiplex polymerase chain reaction and phylogenetic analysis. Dual infection was confirmed using cloning, sequencing, and heteroduplex mobility assay. Results: Among HIV-1/AIDS subjects, 96.1% MSM and 62.5% heterosexual males were infected with subtype B, whereas 66.7% female heterosexuals were infected with CRF01_AE. Most IDUs (84.5%) were infected with CRF07_BC. Four heterosexual males, 2 females and 2 MSM who were not IDUs had CRF07_BC. Forty-nine patients had CRF07_BC/subtype B dual infection and 44 (89.8%) were IDUs. Multivariate logistic regression showed that the odds ratio for dual infection among IDUs who shared syringes >5 times per month was 4.7 (95% confidence interval = 1.3 to 17.7). Phylogenetic analyses revealed that there were 2 main groups of CRF07_BC strains with sporadic transmission between different risk groups. Among 10 IDUs infected with CRF01_AE, 7 cases were clustered with an outbreak happened in 2005 and 3 cases were clustered with other strains from heterosexual population. Conclusions: In Taiwan, 7.8% of HIV-1-infected IDUs had dual infection. It may have important impact to their clinical management. Although CRF07_BC was still remained in IDUs, it has spread to MSM and heterosexual populations.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that causes esophageal remodeling and stricture formation. We compared the clinical course of symptoms, endoscopic findings, histology, and changes in phenotype over time in EoE patients with inflammatory and fibrostenotic phenotypes. METHODS: Data were obtained from EoE patients from three medical centers and followed prospectively. Endoscopic features and histology from index and follow-up endoscopies were recorded. Behavior was classified as inflammatory if endoscopic findings demonstrated furrows or white plaques and as fibrostenotic if endoscopic findings included fixed rings or strictures. RESULTS: Two hundred and fifty-six EoE patients were included in the analysis. The mean age was 32±18 years, 25% of patients were

Objective: An explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan was first reported in 2004 and reach the peak in 2005. The objectives of this study were to investigate the molecular epidemiology of different HIV-1 subtypes and their associated risk factors among Taiwanese IDUs in 2004 and 2005. Methods: Questionnaires and blood specimens were collected from inmates from 4 detention centers and 2 prisons. HIV-1 subtypes were determined using nested polymerase chain reactions with multiplex primers and phylogenetic analyses. A case-control study was conducted to elucidate risk factors associated with CRF07_BC infection. Results: A total of 93.8%, 4%, and 2.2% of 451 inmates with IDU history were infected with CRF07_BC, subtype B, and CRF01_AE, respectively. Besides CRF07_BC, a new outbreak of CRF01_AE infection was identified among IDUs from central region. Multivariate analysis showed that sharing dissolved heroine solution [odds ratio (OR) = 17.2], sharing syringes (OR = 34), number of persons sharing syringes (2 vs. 1, OR = 3.1), and lower educational level (OR = 2.3) were risk factors associated with CRF07_BC infection. Conclusions: Sharing dissolved heroine solution is a neglected risk factor associated with HIV-1 infection and it should be emphasized in the AIDS education and harm reduction programs immediately.

Background: Patients are frequently referred for evaluation of extraesophageal (EXT) symptoms (cough, hoarseness, globus sensation) presumably related to gastroesophageal reflux disease (GERD). 24 hour pH/impedance is the most sensitive test for the diagnosis of GERD, however limited data exist in examining the relationship between distal and proximal impedance episodes in patients with EXT symptoms versus classic reflux symptoms. Aim: To compare the number and percentage of proximal impedance episodes in patients with EXT symptoms to those with classic GERD symptoms undergoing 24 hour pH/impedance testing. Patients & Methods: A retrospective review of adult patients undergoing esophageal manometry and 24 hour pH/impedance studies off acid suppressing therapy between 20062011 was performed. Indications for these studies included typical GERD symptoms (heartburn and regurgitation) or atypical symptoms (cough, asthma, hoarseness or globus sensation). GERD was defined using the validated Johnson-DeMeester (JD) score. The results of the esophageal manometry and 24 hour pH/impedance studies between the classic GERD and EXT groups were compared using Chi squared test and students independent t-test. Continuous data is expressed as means (sd). Results: A total of 220 patients were included in the analysis [172 GERD vs. 48 EXT]. GERD and EXT groups were similar in race and gender, however GERD patients were younger than EXT patients [46 (13) years vs. 50 (8) years, p = 0.048]. There was no significant difference between GERD and EXT in the mean number of proximal impedance episodes [33 (22) vs. 28 (22), p = 0.188], the percentage of proximal impedance episodes migrating from the distal esophagus [55 (20) % vs. 50 (17) %, p=0.178), or the mean number of distal impedance episodes [57 (33) vs. 49 (34), p = 0.157]. There was no significant difference between GERD and EXT with regards to mean lower esophageal sphincter pressures [13.3 (11) mmHg vs. 15.3 (7.8) mmHg, p = 0.251] or mean esophageal amplitude [95.4 (44.6) mmHg vs. 84.9 (41.0) mmHg, p=0.146]. Based on 24 hour pH monitoring there was no significant difference between the classic GERD and EXT groups in the JD scores [22.6 (33) vs 17.8 (22), p = 0.358] or percent total time pH ,4 [4.6 (5.3) vs. 4.2 (5.3), p = 0.642]. There was a significant correlation between the number of proximal and distal episodes between the two groups (R = 0.724, p , 0.001). Conclusion: Patients with EXT symptoms are similar to classic GERD patients in the number proximal impedance reflux episodes and percentage of distal episodes migrating to the proximal esophagus. Furthermore, both groups have a similar degree of acid reflux.