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Chien-Yu Lin,1 Tzu-I Wu,1,2 Szu-Chun Yang1 1Division of Thoracic Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, TaiwanCorrespondence: Szu-Chun Yang, Email yangszuchun@gmail.comPurpose: This study aimed to estimate the costs associated with adverse events (AEs) in advanced lung cancer patients treated with first-line therapies.Subjects and Methods: All patients with advanced lung cancer diagnosed between 2011 and 2019 were identified from the Taiwan National Cancer Registry. First-line treatment was defined as a therapy that began within 30 days before and 90 days after the diagnosis. We defined a newly-developed AE as one established after first-line treatment had commenced, with the contingency that the patient had not been diagnosed with the AE within one year prior to the outset of therapy. One patient with a specific AE was matched on age, sex, and regimens with four patients without the AE. Payments incurred over the same period of time in the two groups were compared to estimate the AE-related costs.Results: A total of 27,376 patients receiving first-line targeted therapy, immunotherapy, or chemotherapy were identified. Clinical characteristics of 15,454 treatment episodes with a specific AE and 61,816 treatment episodes without the AE were well balanced. The costliest AEs of any severity were sepsis/septicemia, neuropathy, and acute kidney injury, with the respective average incremental costs of 10101, 9982, and 7839 USD. The costliest severe AEs requiring hospitalization were sepsis/septicemia, interstitial lung disease/pneumonitis, and neuropathy, with mean incremental costs of 22483, 10645, and 10120 USD, respectively.Conclusion: Costs associated with AEs in advanced lung cancer patients treated with first-line therapies were substantial. These estimates could be adopted for future cost-effectiveness analyses of new lung cancer treatments.Keywords: adverse event, side effect, cost, lung cancer, utilization

Li-Yu Chen,1 Chen-Yu Wang,1,2 Chi-Ying Lin,3 Ming-Jui Tsai,3 Wei-Hsun Shen,1 Pei-Jhih Li,1 Lin-Chu Liao,1 Chih-Fen Huang,4,5 Chien-Chih Wu4 1Department of Pharmacy, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; 2National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; 4Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; 5School of Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Chien-Chih Wu, Department of Pharmacy, National Taiwan University Hospital, 7 Chung Shan S. Road, Taipei, Taiwan, Email 101440@ntuh.gov.tw; r93451011@gmail.comBackground: In the field of postoperative care, infections caused by Gram-positive bacteria pose a major clinical challenge. Vancomycin is a key therapeutic agent whose efficacy is greatly influenced by renal function, particularly by augmented renal clearance (ARC). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) is an easy and commonly used method to predict ARC; however, it is not well studied to determine vancomycin dose. In this study, we examined the effectiveness of the CKD-EPI equation in determining ARC and optimizing the dose of vancomycin for surgical ward patients.Methodology: A retrospective observational study was conducted to examine 158 surgical ward patients receiving vancomycin. Data on demographics, medical history, and vancomycin dosing were collected. Renal function was evaluated using the CKD-EPI equation, with ARC defined as eGFR ≥ 96.5 mL/min/1.73 m2. Vancomycin pharmacokinetics were calculated using the ClinCalc tool.Results: ARC was in 54% of the patients. Compared with patients without ARC, those with ARC were younger and had lower serum creatinine levels. They also required higher vancomycin doses but had lower trough concentrations and 24-hour area-under-the-curve values. A significant correlation was observed between eGFR and vancomycin clearance, with eGFR > 96.5 mL/min/1.73 m2 necessitating higher vancomycin doses (> 45 mg/kg/day) to achieve the desired area under the curve to minimum inhibitory concentration ratio.Conclusion: For surgical ward patients with CKD-EPI eGFR ≥ 96.5 mL/min/1.73 m2, a vancomycin dosage of > 45 mg/kg/day may be recommended to reach effective therapeutic levels. Overall, this study emphasizes the importance of tailoring vancomycin therapy depending on renal function to ensure efficacy and mitigate the risk of antimicrobial resistance in surgical ward patients.Keywords: augmented renal clearance, vancomycin, surgery

Sherin George Shaji,1 Pratikkumar Patel,1 Umar-Farouk Mamani,1 Yuhan Guo,1 Sushil Koirala,1 Chien-Yu Lin,1 Mohammed Alahmari,1 Evanthia Omoscharka,2 Kun Cheng1 1Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA; 2Department of Pathology, University Health/Truman Medical Center, School of Medicine, University of Missouri-Kansas City, Kansas, MO, USACorrespondence: Kun Cheng, Email chengkun@umkc.eduIntroduction: The tumor microenvironment (TME) of pancreatic cancer is highly immunosuppressive and characterized by a large number of cancer-associated fibroblasts, myeloid-derived suppressor cells, and regulatory T cells. Stimulator of interferon genes (STING) is an endoplasmic reticulum receptor that plays a critical role in immunity. STING agonists have demonstrated the ability to inflame the TME, reduce tumor burden, and confer anti-tumor activity in mouse models. 2’ 3’ cyclic guanosine monophosphate adenosine monophosphate (2’ 3’-cGAMP) is a high-affinity endogenous ligand of STING. However, delivering cGAMP to antigen-presenting cells and tumor cells within the cytosol remains challenging due to membrane impermeability and poor stability.Methods: In this study, we encapsulated 2’ 3’-cGAMP in a lipid nanoparticle (cGAMP-LNP) designed for efficient cellular delivery. We assessed the properties of the nanoparticles using a series of in-vitro studies designed to evaluate their cellular uptake, cytosolic release, and minimal cytotoxicity. Furthermore, we examined the nanoparticle’s anti-tumor effect in a syngeneic mouse model of pancreatic cancer.Results: The lipid platform significantly increased the cellular uptake of 2’ 3’-cGAMP. cGAMP-LNP exhibited promising antitumor activity in the syngeneic mouse model of pancreatic cancer.Discussion: The LNP platform shows promise for delivering exogenous 2’ 3’-cGAMP or its derivatives in cancer therapy.Keywords: 2’ 3’-cGAMP, cold tumor, innate immunotherapy, lipid nanoparticle, cytosolic delivery

Horng-Chyuan Lin,1– 3 Meng-heng Hsieh,1,2 Yu-Lun Lo,1,2 Hung-Yu Huang,1,2 Shih-Wei Huang,1,2 Chien-Da Huang,1,2 Po-Jui Chang,1,2 Chun-Yu Lo,1,2 Ting-Yu Lin,1,2 Yueh-Fu Fang,1,2 Shu-Min Lin,1,2 Chun-Yu Lin,1,2,* Ying-Huang Tsai1,2,4,* 1Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Respiratory Therapy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun-Yu Lin, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8467, Fax +886-3-3282474, Email pitiful1984@gmail.com Ying-Huang Tsai, Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8470, Fax +886-3-3282474, Email chestmed@cgmh.org.twBackground: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity.Methods: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results.Results: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α 1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product.Conclusion: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.Keywords: TIMP-1, non-cystic fibrosis bronchiectasis, clinical severity

Long-Fei Xia,1 Jing-Bo Li,2 Guo-Sheng Tian,2 Wei-Ran Jiang,3 Yao-Shuang Li,1 Chen-Ying Lin,1 Hui-Na Qiu,2 Fan Wu,4 Jun-Jia Wang,5 Chun-Jun Li,2 Jing-Na Lin2 1Tianjin Union Medical Center, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, 300121, People’s Republic of China; 3Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA; 4School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 5Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of ChinaCorrespondence: Jing-Na Lin; Chun-Jun Li, Email 13207628978@163.com; li_chunjun@126.comObjective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM).Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression.Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model.Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.Keywords: atherosclerotic cardiovascular disease, ASCVD, type 2 diabetes, T2DM, sarcopenia, fat content, muscle mass

Chao-Ying Chen,1,2 Kuan-Ying Lee,3 Xavier CC Fung,4 Ji-Kang Chen,5 Yu-Chen Lai,6 Marc N Potenza,7– 12 Kun-Chia Chang,13,14 Chuan-Yin Fang,6 Amir H Pakpour,15 Chung-Ying Lin16– 20 1School of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2New Taipei City Tucheng Hospital (Chang Gung Medical Foundation), Department of Pediatric Internal Medicine, New Taipei City, Taiwan; 3Department of Child and Adolescent Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan; 4Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong; 5Department of Social Work, Chinese University of Hong Kong, New Territories, Hong Kong; 6Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 621, Taiwan; 7Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; 8Connecticut Mental Health Center, New Haven, CT, USA; 9Connecticut Council on Problem Gambling, Wethersfield, CT, USA; 10Child Study Center, Yale School of Medicine, New Haven, CT, USA; 11Department of Neuroscience, Yale University, New Haven, CT, USA; 12Wu Tsai Institute, Yale University, New Haven, CT, USA; 13Department of General Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan; 14Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 15Department of Nursing, School of Health and Welfare, Jönköping University, Jönköping, Sweden; 16Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 17Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 18Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 19Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 20INTI International University, Nilai, Negeri Sembilan, 71800, MalaysiaCorrespondence: Kun-Chia Chang, Department of General Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan, Tel +886-6-2795019 ext. 1532, Fax +886-6-2797659, Email kunchiachang0517@gmail.com Chuan-Yin Fang, Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 621, Taiwan, Email 04969@cych.org.twBackground: Problematic use of internet (PUI) may have negative impacts on psychological distress and quality of life (QoL). This situation might be more profound in people with attention-deficit/hyperactivity disorder (ADHD) due to poorer behavioral control and regulatory capacity. However, there is little evidence regarding mediated effects in the associations between PUI, psychological distress, and QoL in people with ADHD.Aims: To investigate mediating effects of psychological distress in the associations of problematic smartphone use (PSPU), problematic use of social media (PUSM), and problematic gaming (PG) with QoL in individuals with ADHD.Methods and Procedures: PUI behaviors of participants with ADHD (n = 99) were assessed using the Smartphone Application-Based Addiction Scale, Bergen Social Media Addiction Scale, and Internet Gaming Disorder-Short Form. Psychological distress was assessed using the Depression, Anxiety, Stress Scale and QoL using the Kid-KINDL.Outcomes and Results: Psychological distress mediated the associations between PUI and different domains of QoL, except for self-esteem QoL. There were also positively direct effects between PG and physical QoL, PUSM and friends’ QoL, and PSPU and physical QoL.Conclusions and Implications: PUI may associate with poor QoL in people with ADHD via psychological distress. Programs on reducing PUI for people with ADHD are needed.Keywords: attention-deficit/hyperactivity disorder, ADHD, impulsive behavior, addictive behavior, internet, psychological distress, quality of life

Hsiao-Mei Hsu,1 Hsin-I Tsai,2– 4 Wei-Chen Lee,4,5 Chih-Chi Wang,6,7 Ming-Chin Yu,3,4,8 Shi-Ming Lin,4,9 Chun-Yen Lin,4,9 Chi-Huan Wu,4,9 Chao-Wei Lee3– 5 1Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Anesthesiology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan; 4College of Medicine, Chang Gung University, Taoyuan, Taiwan; 5Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 7Division of General Surgery, Department of Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 8Department of Surgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 9Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Chao-Wei Lee, Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Guishan, No. 5, Fuxing St., Guishan District, Taoyuan City, 33305, Taiwan, Tel +886-975366192, Email alanchaoweilee@hotmail.comAbstract: Surgical resection remains one of the most effective curative therapies for HCC. However, the majority of patients have advanced unresectable diseases upon presentation. It is of paramount importance to raise the resectability of patients with HCC. The remarkable objective response rate reported by Phase III IMbrave150 trial has led to the concept of “Atezo/Bev followed by curative conversion (ABC conversion)” for initially unresectable HCC. With this revolutionary treatment strategy, the concept of surgical resection for HCC should be amended. The current opinion illustrated three extended surgical concepts, which could be integrated into clinical practice in the era of immune checkpoint inhibitors (ICI).Keywords: hepatocellular carcinoma, liver resection, surgery, immune checkpoint inhibitors, immunotherapy

Mohsen Saffari,1,2,* I-Hua Chen,3,* Po-Ching Huang,4 Kerry S O’Brien,5 Yi-Ping Hsieh,6 Ji-Kang Chen,7 Yun-Hsuan Chang,8– 11 Xingyong Jiang,12 Nadia Bevan,5 Yen-Ling Chang,13 Jung-Sheng Chen,14 Ching-Chung Tsai,15,16 Mark D Griffiths,17 Chung-Ying Lin4,18– 20 1Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran; 2Health Education Department, Faculty of Health, Baqiyatallah University of Medical Sciences, Tehran, Iran; 3Chinese Academy of Education Big Data, Qufu Normal University, Qufu, People’s Republic of China; 4Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5School of Social Sciences, Monash University, Melbourne, Australia; 6Department of Social Work, College of Nursing and Professional Disciplines, University of North Dakota, Grand Forks, ND, USA; 7Department of Social Work, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; 8Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Department of Psychology, National Cheng Kung University, Tainan, Taiwan; 11Institute of Genomics and Bioinformatics, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 12Yangan Primary School of Qionglai City, Qionglai, People’s Republic of China; 13Department of Family Medicine, Cardinal Tien Hospital, New Taipei, Taiwan; 14Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; 15Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; 16School of Medicine, I-Shou University, Kaohsiung, Taiwan; 17International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 18Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 19Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 20Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan*These authors contributed equally to this workCorrespondence: Chung-Ying Lin, Institute of Allied Health Sciences, Department of Occupational Therapy, Department of Public Health, Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701401, Taiwan, Tel +886 6 2353535 ext. 5106, Fax +886 6 2367981, Email cylin36933@gmail.com Ching-Chung Tsai, Department of Pediatrics, E-Da Hospital, School of Medicine, I-Shou University, 1 Yi-Da Road, Kaohsiung, 824005, Taiwan, Email u101130@gmail.comIntroduction: Preventative factors in young people’s physical inactivity require further understanding, including related psychosocial factors (eg, body image and weight stigma). The Tendency to Avoid Physical Activity and Sport Scale (TAPAS) is a recently developed instrument to address this issue and the present study examined its psychometric properties among Chinese university students particularly in relation to patterns across sex, physical activity (PA) level, and weight status.Methods: Using a convenience sample of 3142 students (mean age = 19.8 years; 56% female) in mainland China, data were collected using an online survey between August and October 2022. Psychometric instruments including the Weight Bias Internalization Scale, 21-item Depression, Anxiety and Stress Scale, and International Physical Activity Questionnaire Short Form were administered along with the TAPAS to assess convergent and discriminant validity. Multi-group confirmatory factor analysis (CFA) assessed the measurement invariance across specific groups.Results: The unidimensional structure of the scale was confirmed through CFA (CFI=0.995; RMSEA=0.046). All configural, metric and scalar models of invariance indicated that the scale was invariant across sex, PA level, and weight status. Acceptable convergent and discriminant validity for the scale were found.Conclusion: The TAPAS is a suitable instrument to assess body image and weight stigma concerns for avoiding physical activity and sport among Chinese university students.Keywords: confirmatory factor analysis, factor structure, psychometrics, weight stigma, young adults, China

Yao-Shuang Li,1,2,&ast; Yan-Lan Liu,2,&ast; Jun-Jia Wang,2,3 Nahal Haghbin,4 Xiao-He Wang,5 Wei-Ran Jiang,6 Hui-Na Qiu,2 Long-Fei Xia,1,2 Fan Wu,2,7 Chen-Ying Lin,1,2 Jing-Bo Li,2 Jing-Na Lin2 1Tianjin Union Medical Center, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Endocrinology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, People’s Republic of China; 3Tianjin Union Medical Center, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Institute of Non-Communicable Diseases Control and Prevention, Tianjin Center for Disease Control and Prevention, Tianjin, People’s Republic of China; 6Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA; 7Tianjin Union Medical Center, School of Medicine, Nankai University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing-Na Lin; Jing-Bo Li, Email 13207628978@163.com; doctorljb@aliyun.comObjective: The aim of this study was to elucidate the relationship between specific body composition and the risk of Cognitive Impairment (CI) in middle-aged Type 2 Diabetes Mellitus (T2DM) patients.Methods: This cross-sectional study included 504 hospitalized patients with T2DM from the Department of Endocrinology and Metabolism of the Tianjin Union Medical Center. Subjects were grouped by sex, and cognitive status was assessed using the Montreal Cognitive Assessment (MoCA). The relationship between body composition and cognitive ability was investigated with the use of linear regression analysis. The association between body composition and CI risk was determined by logistic regression analysis.Results: The prevalence of CI was 39.3% in middle-aged T2DM patients. After adjusting for age, education, marriage status, carotid atherosclerosis, cerebrovascular disease and hemoglobin, multiple linear regression analysis showed that lean mass index (LMI), body mass index (BMI) and appendicular skeletal muscle index (SMI) were significant predictors for the MoCA scores in men (p < 0.05). In addition, BMI (OR 0.913, 95% CI 0.840– 0.992) and LMI (OR 0.820, 95% CI 0.682– 0.916) were independent protective factors for CI in males. After adjusted for age, education, marriage status, dietary control of diabetes and cerebrovascular disease, visceral obesity (VO, OR 1.950, 95% CI 1.033– 3.684) and abdominal obesity (AO, OR 2.537, 95% CI 1.191– 5.403) were risk factors for CI in female patients.Conclusion: The results suggest that there may be different mechanisms underlying the relationship of body compositions and cognitive performance between middle-aged male and female patients with T2DM. In addition, our finding of potential determinants of cognitive impairment may facilitate the development of intervention programs for middle-aged type 2 diabetic patients. Nevertheless, more large prospective studies looking at cognition and changes in body composition over time are needed in the future to further support their association.Keywords: cognitive impairment, diabetes, middle age, body composition, sex

Shun-Hua Chen,1 Po-Jen Chen,2 Chiu-Hsiang Lee,3,4 Yu-Ping Wu,3,4 Daniel Kwasi Ahorsu,5,6 Mark D Griffiths,7 Chung-Ying Lin8 1School of Nursing, Fooyin University, Kaohsiung, 83102, Taiwan; 2Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, 824005, Taiwan; 3Department of Nursing, Chung Shan Medical University, Taichung, Taiwan; 4Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan; 5Mental Health Research Centre, the Hong Kong Polytechnic University, Hung Hom, Hong Kong; 6Department of Special Education and Counselling, the Education University of Hong Kong, Tai Po, Hong Kong; 7International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 8Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanCorrespondence: Chiu-Hsiang Lee, Department of Nursing, Chung Shan Medical University, Department of Nursing, Chung Shan Medical University Hospital, 1253F, Jengshin Hall, Taichung, 402, Taiwan, Tel +886-4-24730022 ext. 12216, Email csha528@gmail.com Daniel Kwasi Ahorsu, Department of Special Education and Counselling, The Education University of Hong Kong, B4-1/F-13, Tai Po, Hong Kong, Email daniel.ahorsu@connect.polyu.hkPurpose: Resilience continues to be an important concept in the nursing profession due to its significant role in personal healthcare, patients’ healthcare, and leadership. The present study examined the mediating role of perceived stress in the association between mindfulness and resilience among registered nurses in order to understand their importance among those in the Taiwanese nursing profession.Materials and Methods: Between October and November 2021, a total of 816 registered nurses participated in a cross-sectional survey including psychometric measures assessing perceived stress (Chinese Perceived Stress Scale-10), mindfulness (Chinese Mindful Attention Awareness Scale), and resilience (Chinese Questionnaire of Resilience).Results: Results indicated that perceived stress mediated the association between mindfulness and resilience (standardized coefficient = 0.251, p< 0.001), although there was no significant association between mindfulness and resilience (standardized coefficient = 0.042, p=0.16). This suggests that perceived stress may function as both distress and eustress because mindfulness was not directly associated with resilience but indirectly via perceived stress.Conclusion: Nurses and their administrators should focus on different ways of coping with stress so that they become more resilient in facing other stressors. Future studies may be conducted to examine the mediating role of perceived stress in the association between other coping strategies and resilience among registered nurses.Keywords: coping, healthcare, Taiwan, cross-sectional survey, mediation analysis, mindfulness, resilience

Yin-Han Wang,1 Tsung-Ming Yang,2,3 Ming-Szu Hung,2– 4 Yu-Ching Lin,2– 4 Tien-Pei Fang,1,3 Tzu-Tzu Kuo,5,&ast; Mark D Griffiths,6 Chung-Ying Lin7– 10,&ast; 1Department of Respiratory Therapy, Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 3Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 4Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 5Division of Respiratory Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; 6International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 7Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chung-Ying Lin, Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Tel +886-6-2353535 ext. 5106, Fax +886-6-2367981, Email cylin36933@gmail.com Tzu-Tzu Kuo, Division of Respiratory Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan, Email ed101231@gmail.comPurpose: Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties.Patients and Methods: After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA).Results: Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06).Conclusion: The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.Keywords: adherence, confirmatory factor analysis, COPD, psychometrics

Ming-Jun Tsai,1,2 Cheng-Yu Lin,3 Ji&rcaron;í Trousil,4 Calvin T Sung,5 Mei-Hua Lee,3 Jia-You Fang,3,6,7 Shih-Chun Yang8 1School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Jhong Siao Urological Hospital, Kaohsiung, Taiwan; 3Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; 4Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic; 5Department of Dermatology, University of California, Irvine, CA, USA; 6Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; 7Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 8Department of Microbiology, Soochow University, Taipei, TaiwanCorrespondence: Jia-You Fang, Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, 333, Taiwan, Email fajy@mail.cgu.edu.tw Shih-Chun Yang, Department of Microbiology, Soochow University, 70 Linhsi Road, Shihlin, Taipei, 111, Taiwan, Email scyang@scu.edu.twBackground: Simultaneous anti-Cutibacterium acnes and anti-inflammatory actions are highly beneficial in treating acne vulgaris. In this study, we present novel anti-acne nanovesicles based on liposomes loaded with proteinase K (PK), retinoic acid (RA), and soyaethyl morpholinium ethosulfate (SME) to achieve an effective and safe treatment.Materials and Methods: This study examined in vitro planktonic and biofilm C. acnes elimination, as well as the keratinocyte proliferation suppression by liposomes. The multifunctional liposomes for treating C. acnes in mice were also evaluated.Results: We acquired multifunctional liposomes with a size of 71 nm and zeta potential of 31 mV. The antimicrobial activity of SME was enhanced after liposomal encapsulation according to the reduction of minimum bactericidal concentration (MBC) by 6-fold. The multifunctional liposomes exhibited a synergistically inhibitory effect on biofilm C. acnes colonization compared with the liposomes containing PK or those containing SME individually. The adhesive bacterial colony in the microplate was lessened by 62% after multifunctional liposome intervention. All liposomal formulations tested here demonstrated no cytotoxicity against the normal keratinocytes but inhibited C. acnes-stimulated cell hyperproliferation. The in vitro scratch assay indicated that the liposomal RA—but not free RA—restrained keratinocyte migration. The animal study showed that free RA combined with SME and multifunctional nanovesicles had a similar effect on diminishing C. acnes colonies in the skin. On the other hand, liposomes exhibited superior performance in recovering the impaired skin barrier function than the free control. We also found that RA-loaded nanovesicles had greater skin tolerability than free RA.Conclusion: The cationic liposomes containing dual PK and RA represented a potential treatment to arrest bacterial infection and associated inflammation in acne.Keywords: liposome, acne, Cutibacterium acnes, proteinase K, retinoic acid, skin delivery

Ching-Nung Wu,1,2 Yu-Ming Wang,3,4 Wei-Chih Chen,1 Fu-Min Fang,3,4 Shau-Hsuan Li,5 Tai-Lin Huang,5 Chung-Feng Hwang,1 Yu Lee,6 Chung-Ying Lin,2,7– 9 Sheng-Dean Luo1,10,11 1Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 6Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Kaohsiung, Taiwan; 7Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 11School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Taoyuan, 33302, TaiwanCorrespondence: Chung-Ying Lin, National Cheng Kung University Tainan, 70101, Taiwan, Tel +886-7-731-7123 ext: 2533, Email cylin36933@gmail.com Sheng-Dean Luo, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road, Niaosong District, Kaohsiung City, 83301, Taiwan, Email rsd0323.tw@gmail.comBackground: Few instruments are available for assessing the otorhinologic-related quality of life (QOL) in nasopharyngeal carcinoma (NPC) patients. Therefore, we evaluated whether the 22-item Sinonasal Outcome Test (SNOT-22) could be applied to these patients.Methods: Patients diagnosed with NPC, who had been treated with standard protocol and followed up in our institute between 2019 and 2022, were invited to join the cross-sectional study during their clinic visits. All participants completed the SNOT-22 and Eustachian Tube Dysfunction Questionnaire-7 once they were recruited. Confirmatory factor analysis (CFA) was performed to decide the most suitable model for the underlying SNOT-22 subdomains, along with various validity and reliability tests.Results: We identified a total of 275 patients, with 84 (30.5%) women and 191 (69.5%) men. The mean age was 54.1 years (standard deviation: 11.2). Among these patients, 171 (62.1%) were in late stages, and 260 (94.5%) received chemoradiotherapy as treatment. The median interval between primary RT treatment and questionnaire completion was 50 months (interquartile range: 29– 93). CFA supported a five-factor model for the SNOT-22 for NPC patients, including nasal, ear/facial, sleep, function, and emotion domains. The internal consistency and test-retest reliability of the SNOT-22 domain score were good. In addition, known-group validity was good for the SNOT-22 total score and domain scores according to the disease recurrence status.Conclusion: Psychometric analyses supported the reliability and validity of a five-domain SNOT-22 for assessing otorhinologic-related QOL in NPC patients.Keywords: SNOT-22, nasopharyngeal carcinoma, quality of life, psychometrics, chronic rhinosinusitis

Daniel Kwasi Ahorsu,1 Vida Imani,2 Marc N Potenza,3 Hsin-Pao Chen,4,5 Chung-Ying Lin,6 Amir H Pakpour7,8 1Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong; 2Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran; 3Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; 4Division of Colon and Rectal Surgery, Department of Surgery, E-DA Hospital, I-Shou University, School of Medicine, Kaohsiung, Taiwan; 5College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan; 6Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Social Determinants of Health Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran; 8Department of Nursing, School of Health and Welfare, Jönköping University, Jönköping, SwedenCorrespondence: Amir H Pakpour; Hsin-Pao Chen, Email amir.pakpour@ju.se; shinpao2002@yahoo.com.twPurpose: Exercising can promote good health. However, excessive exercising may have downsides. This study examined the association between exercise addiction and eating disorders and whether the identified association was mediated by psychological distress, insomnia (including sleep quality), and body image concern.Methods: A total of 2088 adolescents (mean age of 15.3 years) participated in this cross-sectional study by questions assessing exercise addiction, eating disorders, psychological distress, insomnia, sleep quality, and body image concern.Results: There were significantly positive relationships between the variables (r=0.12– 0.54, p< 0.01) with effect sizes from small to large. The four potential mediators (ie, insomnia, sleep quality, psychological distress, and body image concern), individually and in total, significantly mediated the association between exercise addiction and eating disorders.Conclusion: The findings suggest that exercise addiction in adolescents may influence eating disorders through multiple pathways, such as insomnia, psychological distress, and body image concerns. Future research should examine these relationships longitudinally and use gathered information to inform intervention development. Clinicians and healthcare workers are encouraged to assess exercise addiction when treating individuals with eating disorders.Keywords: addictive behaviour, exercise, eating disorder, insomnia, stress, compulsive behaviour, adolescent

Yu-Ching Lin,1,2,&ast; Chung-Ying Lin,3– 6,&ast; Chia-Wei Fan,7 Chieh-Hsiu Liu,8 Daniel Kwasi Ahorsu,9 Duan-Rung Chen,10 Hui-Ching Weng,3,11 Mark D Griffiths12 1Department of Physical Medicine and Rehabilitation, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Department of Occupational Therapy, AdventHealth University, Orlando, FL, USA; 8Department of Geriatrics and Gerontology, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong; 10Institute of Health Behaviors and Community Sciences, National Taiwan University, Taipei, Taiwan; 11Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 12International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK&ast;These authors contributed equally to this workCorrespondence: Hui-Ching Weng, Institute of Allied Health Sciences and Institute of Gerontology, College of Medicine, National Cheng Kung University, 1 University Road, East District, Tainan City, 70101, Taiwan, Tel +886-6-2353535 ext. 5986, Fax +886-6-3028175, Email hc6127@mail.ncku.edu.twPurpose: The present study compared two nationally representative cohort datasets concerning Taiwan residents’ healthy behaviors, subjective health outcomes, generalized trust, and accessibility to health promotion resources.Patients and Methods: The Taiwan Social Change Survey (TSCS) was conducted in two waves ten years apart: 2011 cohort (n = 1021; 48.4% males) and 2021 cohort (n = 1425; 47.4%) cohorts. Descriptive statistics were calculated to compare the two TSCS datasets. Then, multiple regression models were constructed with health outcome as the dependent variable, and demographics and other key components as independent variables.Results: The 2011 TSCS cohort showed higher prevalence for cigarette smoking (30.8% vs 25.2%; p=0.002), alcohol drinking (52.5% vs 24.3%; p< 0.001), exercise habits (52.7% vs 48.0%; p=0.02), and better fruit and vegetable accessibility (Mean=3.91 vs 3.82; p=0.04). The 2021 TSCS cohort reported higher body mass index (Mean=24.20 vs 23.63; p< 0.001), less residency in urban areas (22.4% vs 31.1%; p< 0.001), better jogging accessibility (4.14 vs 4.05; p=0.006), higher generalized trust (2.26 vs 2.17; p=0.001), and greater internet usage (3.43 vs 2.89; p< 0.001). The regression model showed that exercise habits (standardized coefficient=0.20 and 0.10; p< 0.001) and generalized trust (standardized coefficient=0.11 and 0.11; p=0.004 and < 0.001) were consistently associated with health outcomes in both cohorts. Additionally, internet use (standardized coefficient=− 0.07; p=0.026) and alcohol drinking behaviors (standardized coefficient=− 0.07; p=0.0022) were negatively associated with health outcomes in the 2021 cohort.Conclusion: The present study demonstrated the trends and changes over 10 years regarding multiple health-related components among Taiwan residents. The study’s findings provide insight into education promotion programs to reduce unhealthy behaviors as well as enhancing generalized trust building and developing healthy behaviors for Taiwan residents.Keywords: health behavior, health promotion, COVID-19, Taiwan, trust

Po-Ching Huang,1 Ching-Hsia Hung,1,2 Guan-Wei Chen,3 Ciaran Cashin,3 Mark D Griffiths,4 Wen-Chi Yang5,6 &ast;, Hsiao-Wen Wang3 &ast;, Chung-Ying Lin1,7– 9&ast;, Nai-Ying Ko10 1Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Hydraulic and Ocean Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan; 4International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 5Division of Hematology and Medical Oncology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 6Faculty of School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chung-Ying Lin, Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, 1 University Rd, Tainan, 701, Taiwan, Tel +886 6-2353535 ext. 5106, Fax +886 6-2367981, Email cylin36933@gmail.comPurpose: The duties related to COVID-19 control and prevention may have caused psychological stress for the individuals in charge (eg, frontline government workers) and have reportedly led to mental health issues, such as insomnia and post-traumatic stress disorder (PTSD). However, the prevalence of these COVID-19-related disorders and their associated factors remain unclear. Therefore, the purpose of the present study was to investigate the prevalence rates of insomnia, PTSD, COVID-19-related self-stigma, and smartphone addiction, along with the identification of risk factors and protective factors for Taiwan frontline government workers with COVID-19 pandemic control duties.Methods: The survey was carried out with 151 participants between September and October 2021. All participants completed the Fear of COVID-19 Scale (assessing fear of COVID-19), Self-Stigma Scale (assessing self-stigma during the COVID-19 pandemic), Smartphone Application-Based Addiction Scale (assessing the risk of smartphone addiction), Insomnia Severity Index (assessing insomnia), Impacts of Event Scale-6 (assessing PTSD), and a self-designed set of questions assessing trait resilience.Results: The results showed that the prevalence rate was 31.1% for insomnia and 33.8% for PTSD. Furthermore, service duration (adjusted odds ratio [AOR] = 0.93; 95% confidence interval [CI] = 0.86, 0.999) and trait resilience (AOR = 0.19; 95% CI = 0.08, 0.46) were protective factors and fear of COVID-19 (AOR = 1.91; 95% CI = 1.02, 3.57) was a risk factor for insomnia. Fear of COVID-19 (AOR = 2.63; 95% CI = 1.35, 5.14), self-stigma (AOR = 3.62; 95% CI = 1.19, 11.02), and smartphone addiction (AOR = 1.09, 95% CI = 1.001, 1.19) were risk factors, and trait resilience was a protective factor (AOR = 0.58; 95% CI = 0.29, 1.17) for PTSD.Conclusion: The findings demonstrated a high prevalence of insomnia and PTSD. Risk-reducing strategies and protective factor promotion strategies are recommended to help reduce the symptoms of insomnia and PTSD among Taiwan frontline government workers.Keywords: mental health, insomnia, post-traumatic stress disorder, smartphone addiction, village officer

Meng-Hsueh Hsieh,1 Yu-Ching Chen,2 Chun-Heng Ho,1,&ast; Chung-Ying Lin2– 5,&ast; 1Department of Industrial Design, College of Planning and Design, National Cheng Kung University, Tainan, Taiwan; 2Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chung-Ying Lin, Institute of Allied Health Sciences, Department of Public Health, Department of Occupational Therapy, Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Email cylin36933@gs.ncku.edu.tw Chun-Heng Ho, Department of Industrial Design, College of Planning and Design, National Cheng Kung University, Tainan, Taiwan, Email hoch@gs.ncku.edu.twPurpose: Diabetes knowledge is important for people with type 2 diabetes mellitus (DM) to improve their health. Therefore, it is important to validate an instrument for assessing diabetes knowledge. The present study aimed to validate the 24-item Diabetes Knowledge Questionnaire (DKQ).Patients and Methods: The 24-item DKQ and Diabetes-specific Quality of Life Module (DMQoL) were administered to 425 patients (mean±SD age=58.4± 11.6) with type 2 DM.Results: The 24-item DKQ was first examined for its factor structure using exploratory factor analysis (EFA). Items with low factors loadings were removed and 18 items were retained to make a DKQ-18. In DKQ-18, five factors were identified, which were named as diabetes etiology and symptoms (F1), intermediate nursing (F2), complications (F3), diet and treatment (F4), and elementary nursing (F5). The DKQ-18 had satisfactory internal consistency (Cronbach’s α= 0.732 and McDonald’s ω=0.748), good known-group validity (participants with a higher level of education showed better score in DKQ-18; participants with HbA1c ≤ 7 had better score in DKQ-18 compared to group of HbA1c level > 8.5), acceptable test–retest reliability (r=0.69), adequate responsiveness (DKQ-18 can detect knowledge change), and concurrent validity with DMQoL.Conclusion: The DKQ-18 is a valid measure for assessing diabetes knowledge. The DKQ-18 could evaluate participants’ diabetes knowledge and improve their diabetes knowledge and self-care through a diabetes team and serve as a tool to evaluate the knowledge of participants with type 2 DM.Keywords: diabetes mellitus, knowledge, diabetes care, self-care, psychometrics

Iqbal Pramukti,1,&ast; Carol Strong,2 I-Hua Chen,3 Cheng-Fang Yen,4– 6 Ahmad Rifai,7 Kusman Ibrahim,8 Moses Glorino Rumambo Pandin,9 Hema Subramaniam,10 Mark D Griffiths,11 Chung-Ying Lin,2,12– 14,&ast; Nai-Ying Ko7,&ast; 1Department of Community Health Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Chinese Academy of Education Big Data, Qufu Normal University, Qufu City, Shandong, People’s Republic of China; 4Department of Psychiatry, School of Medicine College of Medicine, Kaohsiung Medical University, Kaohsiung, 802, Taiwan; 5Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, 802, Taiwan; 6College of Professional Studies, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; 7Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Medical Surgical Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, Indonesia; 9Faculty of Humanities, Universitas Airlangga, Gubeng, East Java, Indonesia; 10Department of Software Engineering, Faculty of Computer Science and Information Technology, Universiti Malaya, Kuala Lumpur, Malaysia; 11International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 12Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 13Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 14Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan&ast;These authors contributed equally to this workCorrespondence: Iqbal Pramukti, Department of Community Health Nursing, Faculty of Nursing, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km.21, Jatinangor, Sumedang, West Java, Indonesia, Tel +6222-779-5596, Fax +6222-779-5596, Email iqbal.pramukti@unpad.ac.id Chung-Ying Lin, Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Tel +886-6-2353535-5106, Fax +886-6-2367981, Email cylin36933@gmail.comBackground: As the number of COVID-19 cases grows worldwide, one solution to the global pandemic is vaccination. Unfortunately, the hesitancy of receiving vaccines is still high, particularly among younger age groups (eg, students). Because the hesitancy of receiving vaccines is an important issue, instruments have been developed to assess vaccine hesitancy. Moreover, the use of these instruments among specific groups such as students is of critical importance.Aim: The present study examined the psychometric properties of the nine-item MoVac-COVID19S (also known as the DrVac-COVID19S) including its measurement invariance among university students in three different countries (ie, Taiwan, Indonesia, and Malaysia).Methods: A multi-country, web-based cross-sectional survey study was conducted among 1809 university students, recruited from the three countries from May to September 2021. The nine-item scale was translated into Traditional Chinese, Bahasa Indonesian, and Malay.Results: The results of the confirmatory factor analysis indicated that the one-factor structure of the MoVac-COVID19S was fully supported among Indonesian and Malay participants (comparative fit index [CFI] = 0.991 and 0.998; Tucker-Lewis index [TLI] = 0.997 and 0.987; root mean sqaure error of approximation [RMSEA] = 0.040 and 0.071; and standardized root mean square residual [SRMR] = 0.014 and 0.039). Moreover, the four-factor structure was supported among Indonesian, Malay, and Taiwanese participants (CFI = 0.998, 0.998, and 0.985; TLI = 0.997, 0.996, and 0.973; RMSEA = 0.044, 0.038, and 0.091; and SRMR = 0.013, 0.018, and 0.049).Conclusion: The MoVac-COVID19S has good construct validity among university students from three different countries (ie, Taiwan, Indonesia, and Malaysia). The four-factor structure of the MoVac-COVID19S was supported. Therefore, health-care providers may want to assess the four underlying constructs to better understand why a university student accepts or declines COVID-19 vaccine uptake in the three countries. Using the findings, government policymakers and health-care authorities can design appropriate programs to help decrease vaccine hesitancy.Keywords: construct validity, COVID-19, factor analysis, measurement invariance, vaccine acceptance

Zainab Alimoradi,1,&ast; Chung-Ying Lin,2– 5,&ast; Irfan Ullah,6 Mark D Griffiths,7 Amir H Pakpour8 1Social Determinants of Health Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran; 2Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6Kabir Medical College, Gandhara University, Peshawar, Pakistan; 7International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 8Department of Nursing, School of Health and Welfare, Jönköping University, Jönköping, Sweden&ast;These authors contributed equally to this workCorrespondence: Irfan Ullah, Kabir Medical College, Gandhara University, Peshawar, Pakistan, Email irfanullahecp2@gmail.com Amir H Pakpour, Department of Nursing, School of Health and Welfare, Jönköping University, Barnarpsgatan 39, Jönköping, 55111, Sweden, Email amir.pakpour@ju.seBackground: The COVID-19 pandemic is still ongoing and is not yet under control. Evidence regarding the impacts of COVID-19 on psychological distress has been widely reported worldwide, and one of the primary concerns regarding psychological distress is fear (ie, fear of COVID-19). Therefore, having a robust instrument for assessing fear of COVID-19 is important. The present systematic review aimed to synthesize the psychometric evidence evaluated using item response theory (IRT) on the Fear of COVID-19 Scale (FCV-19S).Methods: Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, four academic databases (Scopus, PubMed Central, ProQuest, and ISI Web of Knowledge) were used to search target papers. Keywords used for search were “Fear of COVID-19 Scale” and its abbreviation (ie, “FCV-19S”) and IRT-related terms. The COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist was then applied to evaluate the methodological quality of the reviewed papers. Moreover, psychometric properties using IRT methods were synthesized using a qualitative method.Results: The initial search resulted in 552 papers (73 duplicates) and 479 were screened based on their titles and abstracts. Finally, 16 papers were included for review regarding their methodological quality (via COSMIN) to synthesize the psychometric evidence for FCV-19S. The 16 papers included 21 countries with 16 language versions of FCV-19S.Conclusion: All the psychometric evidence indicated that the seven items in the FCV-19S fit with the concept of fear. The FCV-19S is a strong and valid instrument for assessing fear across different languages. The seven items in the FCV-19S appear to be unidimensional in assessing fear, which indicates that all items are necessary in the FCV-19S.Keywords: COVID-19, fear, item response theory, psychometrics, Rasch, review

I-Hua Chen,1,&ast; Pei-Ling Wu,2,3,&ast; Cheng-Fang Yen,4– 6,&ast; Irfan Ullah,7 Sheikh Shoib,8 Shafi Ullah Zahid,9 Aadil Bashir,10 Naved Iqbal,11 Frimpong-Manso Addo,12 Emma Sethina Adjaottor,12 Gifty Boakye Amankwaah,12 Daniel Kwasi Ahorsu,13 Mark D Griffiths,14 Chung-Ying Lin,15– 18 Amir H Pakpour19 1Chinese Academy of Education Big Data, Qufu Normal University, Qufu City, Shandong, People’s Republic of China; 2School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 3Department of Pediatrics, E-Da Hospital, Kaohsiung, Taiwan; 4Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 5Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, 80756, Taiwan; 6College of Professional Studies, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; 7Kabir Medical College, Gandhara University, Peshawar, Pakistan; 8Sheikh Shoib Department of Psychiatry, Jawahar Lal Nehru Memorial Hospital, Srinagar, India; 9Department of Neurosurgery, Jamhuriat hospital, Kabul, Afghanistan; 10Department of Social Work, University of Kashmir, Kashmir, India; 11Department of Psychology, Jamia Millia Islamia, New Delhi, India; 12Department of Behavioural Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; 13Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong; 14International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 15Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 16Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 17Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 18Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 19Department of Nursing, School of Health and Welfare, Jönköping University, Jönköping, Sweden&ast;These authors contributed equally to this workCorrespondence: Emma Sethina Adjaottor; Chung-Ying Lin, Tel +233 20 816 85080 ; +886-6-2353535-5106, Fax + 886-6-2367981, Email eadjaottor.chs@knust.edu.gh; cylin36933@gmail.comPurpose: The percentage of individuals who were fully vaccinated against COVID-19 was 53% worldwide, 62% in Asia, and 11% in Africa at the time of writing (February 9, 2022). In addition to administrative issues, vaccine hesitancy is an important factor contributing to the relatively low rate of vaccination. The Motors of COVID-19 Vaccination Acceptance Scale (MoVac-COVID19S) was developed to assess COVID-19 vaccination acceptance levels. However, it has only been tested among Taiwanese, mainland Chinese, and Ghanaian populations (Chen et al, 2021; Fan et al, 2021; Yeh et al, 2021). Therefore, the present study examined the construct validity and measurement invariance of the MoVac-COVID19S among individuals from five countries (ie, Taiwan, mainland China, India, Ghana, and Afghanistan).Participants and Methods: A cross-sectional survey study recruited 6053 participants across five countries who completed the survey between January and March 2021. Confirmatory factor analysis (CFA) fit indices were used to examine factor structure and measurement invariance across the five countries.Results: The fit indices of the CFA were relatively good across the countries except for the root mean square error of approximation (RMSEA). Moreover, the four-factor structure (either nine or 12 items) had a better fit than the one-factor structure. However, the four-factor model using nine MoVac-COVID19S items was the only model that had measurement invariance support for both factor loadings and item intercepts across the five countries.Conclusion: The present study confirmed that the MoVac-COVID19S has acceptable psychometric properties and can be used to assess an individual’s willingness to get COVID-19 vaccination.Keywords: factor structure, vaccine hesitancy, young adults

Yao-Chi Chuang,1,2 Pei-Wen Lin,2– 4 Hsin-Ching Lin,2,4– 6 Chun-Tuan Chang,6 Michael Friedman,7,8 Anna M Salapatas,8 Chih-Yun Lin9 1Division of Urology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Division of Glaucoma, Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 4Sleep Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 5Department of Otolaryngology, Robotic Surgery Center and Center for Quality Management, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 6Department of Business Management, Institute of Healthcare Management, National Sun Yat-sen University, Kaohsiung, Taiwan; 7Department of Otolaryngology, Division of Sleep Surgery, Rush University Medical Center, Chicago, IL, USA; 8Department of Otolaryngology, Advanced Center for Specialty Care, Advocate Illinois Masonic Medical Center, Chicago, IL, USA; 9Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCorrespondence: Hsin-Ching Lin, Department of Otolaryngology, Sleep and Robotic Surgery Center, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung District, Kaohsiung City, 833, Taiwan, Tel +886-7-7317123 ext.2533, Fax +886-7-7313855, Email hclin@adm.cgmh.org.tw; enthclin@aol.comObjective: To determine the presence of lower urinary tract symptoms (LUTS), and overactive bladder (OAB) symptoms in men with obstructive sleep apnea/hypopnea syndrome (OSA) and the effects of transoral robotic surgery (TORS) for the treatment of OSA on these conditions.Materials and Methods: One hundred twenty-three patients with a diagnosis of OSA were prospectively enrolled. The evaluations of LUTS and OAB symptoms were based on self-administered questionnaires containing international prostate symptom score (IPSS) and OAB symptom score (OABSS), respectively. Men with an OABSS urgency score of ≥ 2 and sum score of ≥ 3 were considered to have OAB. The therapeutic outcomes were assessed at baseline, and 12 weeks after TORS-OSA Surgery.Results: There were significant differences in IPSS, and OABSS according to OSA severity. After TORS-OSA surgery, significant improvements on OSA severity, daytime quality of life (QoL) and nighttime sleep quality were observed. TORS-OSA surgery was also associated with a statistically significant improvement of LUTS, LUTS QoL score, and OAB symptoms (IPSS 22.1% decrease; IPSS QoL score 21.1% decrease; OABSS17.4% decrease) at post-operative 3 months’ follow-up. The presence of OAB, and severe nocturia was significantly reduced from 22.8% to 11.4% (p=0.001), 5.7% to 0.8% (p=0.031) after TORS-OSA surgery. There were no patients who had acute airway compromise or massive bleeding peri- or post-operatively.Conclusion: TORS upper airway surgery could improve LUTS and OAB symptoms on male patients with OSA in addition to improvement of major parameters of sleep study and sleep-related QoL.Keywords: snoring, obstructive sleep apnea, lower urinary tract symptoms, overactive bladder symptoms, OSA surgery, transoral robotic surgery

Pei-Wen Lin,1,2 Hsin-Ching Lin,2– 5 Chun-Tuan Chang,5 Michael Friedman,6,7 Anna M Salapatas,7 Meng-Chih Lin,2,8 Chih-Yun Lin9 1Division of Glaucoma, Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City; Chang Gung University College of Medicine, Taoyuan City, Taiwan; 2Sleep Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan; 3Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City; Chang Gung University College of Medicine, Taoyuan City, Taiwan; 4Robotic Surgery Center and Center for Quality Management, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan; 5Department of Business Management, Institute of Healthcare Management, National Sun Yat-sen University, Kaohsiung City, Taiwan; 6Department of Otolaryngology, Division of Sleep Surgery, Rush University Medical Center, Chicago City, IL, USA; 7Department of Otolaryngology, Advanced Center for Specialty Care, Advocate Illinois Masonic Medical Center, Chicago City, IL, USA; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City; Chang Gung University College of Medicine, Taoyuan City, Taiwan; 9Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, TaiwanCorrespondence: Hsin-Ching Lin, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung District, Kaohsiung City, 833, Taiwan, Tel +886-7-7317123 ext.2533, Fax +886-7-7313855, Email hclin@adm.cgmh.org.tw; enthclin@aol.comPurpose: Obstructive sleep apnea/hypopnea syndrome (OSA) results in repeated oxygen desaturation, repeated arousals, and episodic nocturnal activation of sympathetic nervous system during sleep. Untreated OSA is strongly associated with an increase of cardio- and cerebrovascular disorders, as well as the damages of ophthalmological microstructures. However, previous literature only simply studied the association between the ophthalmic disorders and OSA. In the present study, we first investigated the alterations of ocular surface and tear film non-invasively with the innovated corneal topographer in untreated OSA patients and normal control subjects. Furthermore, we analyzed in depth whether the correlations between OSA severity and ocular surface exams exist.Participants and Methods: Participants underwent a full-night polysomnography to determine OSA occurrence and severity. All participants subsequently received Ocular Surface Disease Index questionnaire and comprehensive ocular exams, including floppy eyelid syndrome (FES) assessment, oculus scan for tear meniscus height, non-invasive keratograph tear film breakup time (NIKBUT), and ocular surface redness, endothelial cell density, and corneal fluorescein staining.Results: One hundred eighty-one participants were prospectively enrolled in the study. FES was found in 11.5% of the normal control group and 60.0% of the severe OSA group (p=0.0005). There were significant differences in the first-NIKBUT (F-NIKBUT) (p < 0.0001), average-NIKBUT (A-NIKBUT) (p = 0.0007), and redness scores over the nasal bulbar (p = 0.032), temporal bulbar (p < 0.0001), nasal limbal (p = 0.014), and temporal limbal (p < 0.0001) areas among the four groups. F-NIKBUT and A-NIKBUT were significantly shorter in the moderate/severe OSA group (apnea/hypopnea index (AHI) ≥ 15) than in the normal/mild OSA group (AHI < 15) (both p < 0.0001). The redness scores over the temporal bulbar (p < 0.0001) and temporal limbal (p < 0.0001) areas were also significantly different in these two OSA groups. Moreover, F-NIKBUT and A-NIKBUT negatively correlated with AHI. Nasal bulbar redness, temporal bulbar redness, nasal limbal redness, and temporal limbal redness positively correlated with AHI.Conclusion: OSA patients had higher occurrence of FES. The NIKBUT was significantly shorter, and the temporal conjunctival redness scores over bulbar and limbal areas were higher in the moderate/severe OSA group than in the normal/mild OSA group. NIKBUT and conjunctival hyperemia significantly correlated with the severity of untreated OSA.Keywords: snoring, obstructive sleep apnea, ocular surface and tear film

Daniel Kwasi Ahorsu,1,&ast; Iqbal Pramukti,2,&ast; Carol Strong,3 Hsiao-Wen Wang,4 Mark D Griffiths,5 Chung-Ying Lin,3,6– 8 Nai-Ying Ko9 1Department of Rehabilitation Sciences, Faculty of Health & Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong; 2Faculty of Nursing, Universitas Padjadjaran, West Java, Indonesia; 3Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Hydraulic and Ocean Engineering, National Cheng Kung University, Tainan, 701, Taiwan; 5International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 6Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chung-Ying LinInstitute of Allied Health Sciences and Departments of Occupational Therapy and Public Health, Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, TaiwanTel +886-6-2353535-5106Fax +886-6-2367981Email cylin36933@gmail.comCorrespondence: Nai-Ying KoDepartment of Nursing, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, TaiwanTel +886-6-2353535-5838Fax +886-6-2377550Email nyko@mail.ncku.edu.twPurpose: The present study examined the differences between international and local university students in Taiwan regarding COVID-19-related variables, anxiety, and suicidal ideation.Participants and Methods: An online cross-sectional survey (sent via an online link in an email) was carried out comprising university students (n=529). The students were assessed on measures (including validated psychometric instruments) of perceived susceptibility to COVID-19, perceived sufficiency of resources, sources of COVID-19 information, perceived satisfaction with support, anxiety and suicidal ideation.Results: Local students had higher susceptibility to COVID-19 (p< 0.001) but decreased sufficiency with resources (p< 0.001) and anxiety (p< 0.001) compared with international students. Staying with family members, satisfaction with support, and information seeking were the factors that predicted anxiety among international students (all p-values< 0.05), while information seeking predicted local students’ anxiety (p< 0.001). Furthermore, staying with family members, susceptibility to COVID-19, and sufficiency with resources were the factors that predicted suicidal ideation among international students (all p-values< 0.05), while being a male and satisfaction with support predicted suicidal ideation among local students (all p-values< 0.05).Conclusion: International students displayed different COVID-19-related challenges compared with local students. More specifically, international students as compared with local students had lower susceptibility to COVID-19 and higher anxiety. Therefore, healthcare providers should pay more attention to international students’ psychological health and awareness regarding impacts of COVID-19 on health.Keywords: anxiety, COVID-19, university students, suicidal ideation, Taiwan

Wan-Chi Huang,1 Chia-Shuan Chang,2 Chien-Yu Lin,3 Ting-Fu Lai,1 Ming-Chun Hsueh,4 Yung Liao,1,5 Jong-Hwan Park6 1Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, 106, Taiwan; 2Institute of Health Behaviors and Community Sciences, National Taiwan University, Taipei, 100, Taiwan; 3Graduate School of Sport Sciences, Waseda University, Tokorozawa City, Saitama Prefecture, 359-1192, Japan; 4Graduate Institute of Sport Pedagogy, University of Taipei, Taipei City, 11153, Taiwan; 5Faculty of Sport Sciences, Waseda University, Tokorozawa City, Saitama, 359-1192, Japan; 6Health Convergence Medicine Laboratory, Biomedical Research Institute, Pusan National University Hospital, Busan, 49241, KoreaCorrespondence: Jong-Hwan ParkHealth Convergence Medicine Laboratory, Biomedical Research Institute, Pusan National University Hospital, Busan, 49241, KoreaTel/Fax +82-51-240-7071Email parkj@pusan.ac.krPurpose: Sleep, sedentary behavior, and physical activity are the components of the 24-hour model, while the timing of sleep may play a critical role to impact waking behaviors. Therefore, the present study aimed to examine the relationship of sleep timing with sedentary behavior, light-intensity, moderate-to-vigorous-intensity physical activity, and daily steps in older women.Patients and Methods: A total of 90 community-dwelling older women (70.5 ± 5.4 years) were included in our sample. Multiple linear regression models were used to estimate the associations of accelerometer-measured sedentary behavior and physical activity metrics with the three sleep timing indicators (bedtime and wake time, and mid-sleep time). Bedtime and wake time were recorded by the participants, and mid-sleep time was estimated based on the two sleep indicators.Results: Most indicators of sleep timing were negatively associated with moderate-to-vigorous-intensity physical activity (unstandardized coefficient [B]− 0.07 for bedtime and mid-sleep time, p< 0.05) and daily steps (B ranged from − 15.51 for bedtime to − 13.73 for wake time, p< 0.05). No associations of sleep timing were found in sedentary behavior and light-intensity physical activity.Conclusion: The findings suggest that sleep timing should be considered when designing promising strategies or interventions for older women to be physically active.Keywords: sleep timing, circadian clock, modifiable behavior, aging population

Shih-Wei Lee,1,* Yu-Chen Huang,2,3,* Chun-Yu Lin,2,3 Hung-Yu Huang,2,3 Chi-Wei Liu,1 Ming-Tsuen Hsieh,4 Chon-Lin Lee,4– 7 Wen-Yu Chung,8 Kian Fan Chung,9 Chun-Hua Wang,2,3 Han-Pin Kuo10,11 1Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 3College of Medicine, Chang Gung Memorial University, Taoyuan, Taiwan; 4Department of Marine Environment and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Aerosol Science and Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan; 6Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Applied Chemistry, Providence University, Taichung, Taiwan; 8Department of Computer Science and Information Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan; 9Experimental Studies, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK; 10Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan; 11Department of Thoracic Medicine, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Chun-Hua WangDepartment of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road, Taipei 10507, TaiwanTel +886 3 321 1200 ext 8467Email wchunhua@ms7.hinet.netHan-Pin KuoDepartment of Medicine, Taipei Medical University School of Medicine, 250 Wu-Xing Street, Taipei 11031, TaiwanEmail q8828@ms11.hinet.netPurpose: Exposure to polycyclic aromatic hydrocarbons (PAHs) associated with ambient air particulate matter (PM) poses significant health concerns. Increased acute exacerbation (AE) frequency in asthmatic patients has been associated with ambient PAHs, but which subgroup of patients are particularly susceptible to ambient PAHs is uncertain. We developed a new model to simulate grid-scale PM2.5-PAH levels in order to evaluate whether the severity of asthma as measured by the Global Initiative of Asthma (GINA) levels of treatment is related to cumulative exposure of ambient PAHs.Methods: Patients with asthma residing in the northern Taiwan were reviewed retrospectively from 2014 to 2017. PM2.5 were sampled and analysed for PAHs twice a month over a 72-hour period, in addition to collecting the routinely monitored air pollutant data from an established air quality monitoring network. In combination with correlation analysis and principal component analysis, multivariate linear regression models were performed to simulate hourly grid-scale PM2.5-PAH concentrations (ng/m3). A geographic information system mapping approach with ordinary kriging interpolation method was used to calculate the annual exposure of PAHs (ng/m).Results: Among the 387 patients with asthma aged 18 to 93 (median 62), 97 subjects were treated as GINA step 5 (24%). Asthmatics in GINA 5 subgroup with high annual PAHs exposure were likely to have a higher annual frequency of any AE (1 (0– 12), p< 0.0001). Annual PAHs exposure was correlated with the annual frequency of any exacerbation (r=0.11, p=0.02). This was more significant in the GINA 5 subgroup (r=0.29, p=0.005) and in the GINA 5 subgroup with severe acute exacerbations (r=0.51, p=0.002). Annual PAHs exposure, severe acute exacerbation and GINA steps were independent variables that predict annual frequency of any exacerbation.Conclusion: Asthmatic patients in the GINA 5 subgroup with acute exacerbations were more susceptible to the effect of environmental PAHs on their exacerbation frequency. Reducing environmental levels of PAHs will have the greatest impact on the more severe asthma patients.Keywords: polycyclic aromatic hydrocarbons, asthma acute exacerbation, GINA, hourly grid-scale model

Yi-Qing Chen,* Wen-Ting Zhu,* Cai-Yan Lin, Zhong-Wen Yuan, Zhen-Hua Li, Peng-Ke Yan The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Ke YanThe Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of ChinaEmail gysyypk@126.comBackground: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer.Methods: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo.Results: The prepared rapamycin liposomes had a particle size of 100± 5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways.Conclusion: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin’s antitumor effect but also synergistically enhances 5-FU’s chemotherapy effect.Keywords: rapamycin liposomes, 5-fluorouracil, Akt/mTOR, P53, colorectal cancer

Chen-Mao Liao,1,* Chih-Ming Lin,2,* Chin-Chia Kuo,1 Ming-Shu Chen,3 Chun-Yang Huang,4 Ching-Yuan Lin4 1Department of Applied Statistics and Information Science, Ming Chuan University, Taoyuan City 33352, Taiwan; R.O.C.; 2Department of Healthcare Information and Management, Ming Chuan University, Taoyuan City 33352, Taiwan; R.O.C.; 3Department of Healthcare Administration, College of Management and Healthcare, Oriental Institute of Technology, New Taipei City 22061, Taiwan; R.O.C.; 4Department of Laboratory Medicine, Ten Chan General Hospital, Chung-Li, Taoyuan City 32043, Taiwan; R.O.C.*These authors contributed equally to this workCorrespondence: Ming-Shu ChenDepartment of Healthcare Administration, College of Management and Healthcare, Oriental Institute of Technology, No58, Sec. 2, Sichuan Road, Pan-Chiao Dist., New Taipei City 22061, Taiwan; R.O.C.Tel +886-2-77388000 ext. 6223Email tree1013@gmail.comBackground: To continuously improve medical quality and provide clinicians with more accurate blood test reports, this study collected blood quality control data in 2017 from a medical examination laboratory in a teaching level hospital located in Taoyuan City, Taiwan.Material and Methods: The quality control data were arranged and analyzed from daily complete blood count (CBC), including white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and platelets (PLT) recorded by a laboratory blood analyzer. Using the empirical Bayesian method, we estimated the variation of concentrations of the last and current batches to establish a novel control chart with adjusted upper and lower limits for the current batch, and then compared results with the traditional Shewhart method. The average run length (ARL) and sensitivity of the empirical Bayesian method were explored.Results: The study found that ARL showed a qualified capability for the four blood routine tests when using the empirical Bayesian method. Compared to the Levey–Jennings control chart, the novel control chart presents an alert earlier when a deviation occurs and shows a fake alert later when there is no deviation.Conclusion: The parallel tests showed that the longer the time is, the better the test’s proficiency. We concluded that the empirical Bayesian method could be applied effectively to improve the capability of daily control in CBC laboratory tests.Keywords: empirical Bayesian, EB, average run length, ARL, complete blood count, CBC, Levey–Jennings control chart

Chun-Yu Lin,1,2 Yu-Chen Huang,1,2 Hung-Yu Huang,1,2 Fu-Tsai Chung,1,2 Yu-Lun Lo,1,2 Shu-Min Lin,1,2 Chun-Hua Wang,1,2 Han-Pin Kuo3 1Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3College of Medicine, Taipei Medical University, Taipei, TaiwanCorrespondence: Chun-Hua WangDepartment of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kweishan, Taoyuan 33305, TaiwanTel +8863-3281200 ext.8467Fax +8863-3287787Email wchunhua@ms7.hinet.netBackground: The efficacy of antifungal therapy in fungal-associated severe asthma remains controversial.Objective: We aimed to evaluate the differences in the clinical presentation and response to antifungal therapy between severe asthmatics with fungal sensitization and positive fungal isolates.Methods: This retrospective study included 73 patients with severe asthma from January 2004 to December 2017. We examined the presentation, medication, exacerbations, pulmonary function, serum IgE, blood eosinophils, and sputum culture results. Follow-up care was provided to each patient for minimum 3 years.Results: We classified the patients into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n=16); group 2, positive fungal sensitization (n=16); group 3, positive fungal isolates (n=31); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n=10). There were four participants in group 2, 15 in group 3, and 6 in group 4 had received itraconazole therapy for 3 months. Patients in group 3 presented with lower serum IgE level than those in groups 2 and 4. Antifungal therapy significantly improved ACT score during the first year in groups 3 (from 18 [15– 22] to 24 [23– 24], p=0.0004) and resulted in a long-lasting ACT improvement till the third year in group 3 (from 18 [15– 22] to 24 [22– 24], p=0.0013).Conclusion: Antifungal therapy could effectively control the symptoms in patients with severe asthma with positive fungal isolates, contrary to those with merely fungal sensitization; therefore, highlighting the need for a more precise treatment strategy in future for fungal-associated severe asthma.Keywords: fungal-associated asthma, severe asthma, fungal sensitization, antifungal therapy, itraconazole

Chih-Yin Lin,1 Chun-An Yao2 1Department of Neurology, Chang Gung Memorial Hospital, Linkou 333, Taiwan; 2Department of Dermatology, Cathay General Hospital, Taipei, TaiwanCorrespondence: Chun-An YaoDepartment of Dermatology, Cathay General Hospital, 280 Renai Road Sec. 4, Taipei, TaiwanTel +886-2-27082121Fax +886-2-2709-6521Email chunany115@gmail.comAbstract: The outbreak of coronavirus disease 2019 (COVID-19) pandemic has already caused a huge burden to the global healthcare system, with the death toll reached tens of thousands. Although some antiviral agents were identified and used to inhibit viral replication, the management of cytokine storm is also a critical issue. In this article, we reviewed the literature on drug candidates for severe acute respiratory syndrome (SARS-CoV-1) and provided a brief overview of a class of drugs that exert antiviral and anti-inflammatory effects. These molecules mitigated inflammatory cytokine cascades induced by viral infections via Nrf2 activating capacity and might have additional anti-fibrotic and anti-remodeling properties. Besides, their effects on the regulation of scavenger receptors expression by macrophages may offer some benefits to the pulmonary antibacterial defense system after viral infection. The potential roles of these agents assessed on the basis of the pathophysiology of viral pneumonia and acute respiratory distress syndrome were also discussed. Further research is needed to ascertain whether Nrf2 activators are useful in the management of viral pneumonia.Keywords: COVID-19, viral pneumonia, Nrf2 activators, curcumin, sulforaphane, macrolide

Andrew Blauvelt,1 Nianwen Shi,2 Russel Burge,3,4 William N Malatestinic,3 Chen-Yen Lin,3 Carolyn R Lew,2 Nicole M Zimmerman,2 Orin M Goldblum,3 Baojin Zhu,3 Mwangi J Murage3 1Oregon Medical Research Center, Portland, OR, USA; 2IBM Watson Health, Cambridge, MA, USA; 3Eli Lilly and Company, Indianapolis, IN, USA; 4University of Cincinnati, Cincinnati, OH, USACorrespondence: Mwangi J MurageGlobal Patient Outcomes and Real World Evidence (GPORWE), Eli Lilly and Company, LCT – South Building 171-2, Drop Code 5221, 1555 Harding St, Indianapolis, IN 46221, USATel +1-317-460-3619Email murage_mwangi_james@lilly.comBackground: There is lack of real-world treatment pattern comparison data between ixekizumab and adalimumab which are approved for the treatment of moderate-to-severe plaque psoriasis.Objective: To compare real-world treatment patterns among psoriasis patients initiating ixekizumab or adalimumab in the United States.Methods: Psoriasis patients with ≥ 1 claim for ixekizumab or adalimumab between March 1, 2016, and May 31, 2018, were identified (index date = date of first ixekizumab or adalimumab claim) from the IBM Watson Health MarketScan® databases. Patients were required to be continuously enrolled for ≥ 12 months before the index date and followed for a minimum of 6 months until inpatient death, enrollment end, or study end, whichever occurred first. Treatment persistence, adherence, discontinuation, restart, and switching were analyzed. Inverse probability of treatment weighting and multivariable regression modeling were employed to address cohort imbalances and estimate the adjusted risk of non-persistence, discontinuation, and switching, and the odds of adherence.Results: A total of 646 ixekizumab and 3668 adalimumab users were included and followed for a mean of 14.0 and 16.5 months, respectively. Compared to adalimumab, ixekizumab was associated with 19% lower risk of non-persistence (hazard ratio [HR]=0.81, 95% confidence interval [CI]: 0.69– 0.95), 26% lower risk of discontinuation (HR=0.74, 95% CI: 0.62– 0.88), and 28% lower risk of switching (HR=0.72, 95% CI: 0.57– 0.91). Ixekizumab users had higher odds of medication possession ratio ≥ 80% (odds ratio [OR]=1.36, 95% CI: 1.10– 1.69) but similar odds by proportion of days covered ≥ 80% (OR=1.22, 95% CI: 0.98– 1.53).Conclusion: Psoriasis patients treated with ixekizumab demonstrated longer persistency, higher adherence and were less likely to discontinue or switch treatment compared to adalimumab users. However, while patients achieving highly adherent threshold significantly differed by MPR ≥ 80%, it did not by PDC ≥ 80%; hence, further analysis using fixed-length follow-up is required.Keywords: ixekizumab, adalimumab, psoriasis, treatment switching, discontinuation, persistence

Si-Pin Hu, 1 Lei Chen, 2 Chen-Yi Lin, 3 Wei-Hang Lin, 2 Fu-Quan Fang, 4 Meng-Yun Tu 5 1Department of Vascular Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Hepatobiliary Surgery, Ruian People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 5Department of Clinical Laboratory, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Meng-Yun TuDepartment of Clinical Laboratory, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310006, People’s Republic of ChinaTel +86 571 5816 2261Email appletumengyun@sina.cnPurpose: Patients with malignancy are more likely to develop nutritional problems. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic index for evaluating nutritional status. The objective of this study was to assess if preoperative GNRI could be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC) who underwent radical surgery.Patients and Methods: This study included 282 consecutive patients with incident pancreatic ductal adenocarcinoma who were treated with radical surgery. The Cox regression analysis was performed to calculate the overall survival (OS) and assess the prognostic factors. A nomogram was developed based on the results of the multivariate analysis, and the predictive accuracy of the nomogram was assessed.Results: Among the 282 patients, there are 117 males and 165 females. The patients had a mean age of 58.7 ± 13.5 years, with the median follow-up time of 72.9 months (interquartile range, 0.7 to 115.2 months). They were classified into abnormal (GNRI ≤ 98) and normal (GNRI > 98) GNRI groups, respectively. Multivariate Cox analysis showed that age (HR = 1.023), drinking history (HR = 1.453), tumor grade (HR = 1.633), TNM stage (HR = 1.921), and GNRI (HR = 1.757) were significantly associated with OS. Based on the above variables, the nomogram was established. The concordance index (C-index) and time-dependent receiver operating characteristics curve (tdROC) showed the nomogram was superior to TNM grade and tumor grade in predicting the OS of patients with PDAC.Conclusion: GNRI could be a useful prognostic indicator in patients with PDAC who received surgery. Based on the GNRI and the other clinical indicators, we developed a nomogram model that can provide an accurate estimation of OS in patients with PDAC after radical surgery.Keywords: pancreatic ductal adenocarcinoma, the geriatric nutritional risk index, overall survival, nomogram

Chien-Yu Lin,1,2 Bohyeon Kim,3 Yung Liao,4,* Jong-Hwan Park3,*1Graduate School of Sport Sciences, Waseda University, Tokorozawa, Japan; 2Institute of Health Behaviors and Community Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; 3Health Convergence Medicine Research Group, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea; 4Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan*These authors contributed equally to this workIntroduction: Previous investigations on factors associated with depression were highly focused on personal characteristics and health behaviors; however, few studies used an ecological perspective on the issue, much less on sex differences. This study examined the factors associated with depression, including any sex differences.Methods: A total of 1025 Taiwanese adults older than 65 years were recruited. Their personal demographics, lifestyle behaviors, and perceived environmental factors were obtained through a telephone-based survey. The multiple factors associated with depression in older adults were examined using logistic regression analyses.Results: Fully logistic regression analyses revealed that poor self-rated health (odds ratio =2.54) was correlated with a greater likelihood of depression. Aside from poor self-rated health, being older, sufficient leisure time spent in walking, and perceptions of a safe environment were associated with lower risks of depression in older men, whereas having hypertension and excessive TV viewing were associated with higher risks of depression in older women.Conclusion: Apart from self-rated health, sex differences in the associations of factors such as leisure-time walking, TV watching, and safe traffic environment with depression were observed among older adults. Strategies applied for geriatric depression prevention should take into consideration different sex group.Keywords: geriatric depression, older adults, multiple factors

Wei-Te Lei,1 Hsin Hui Lin,2 Mu-Chieh Tsai,1 Hua-His Hung,1 Yu-Jyun Cheng,1 Shu-Jung Liu,3 Chien Yu Lin,1 Tzu-Lin Yeh4 1Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan; 2Department of Family Medicine, Taipei Mackay Memorial Hospital, Taipei, Taiwan; 3Department of Medical Library, MacKay Memorial Hospital, Tamsui Branch, New Taipei City, Taiwan; 4Department of Family Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan Purpose: Childhood reactive airway diseases (RADs) are concerning problems in children’s airways and may be preceded by bronchiolitis and may progress to childhood asthma. The severity of the disease is indicated by deterioration in pulmonary functions, increased usage of rescue medications, and recurrent wheezing episodes. Macrolides have both antimicrobial and anti-inflammatory functions and have been used as adjunctive therapy in childhood RADs. Patients and methods: We conducted a meta-analysis to evaluate the effect of macrolides in children with RAD. Literature searches were systematically conducted using an electronic database from inception to August 2018. The Cochrane review risk of bias assessment tool was used to assess the quality of each randomized controlled trial. Results: Sixteen randomized controlled trials comprising 1,415 participants were investigated in this meta-analysis. Children treated with macrolide therapy showed significantly better pulmonary functions in both forced expiratory volume in one second (% predicted) (difference in means=-9.77, 95% CI=-14.18 to -5.35, P

Jui-Ming Liu,1–3,* Chien-Yu Lin,4,* Heng-Chang Chuang,1 Ren-Jun Hsu3,5,6 1Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2Department of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 4Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan; 5Biobank Management Center of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 6Department of Pathology and Graduate Institute of Pathology and Parasitology, the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan *These authors contributed equally to this work Objective: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) patients has been reported to exacerbate the course of psoriasis. We aimed to assess the impact of ADT on the subsequent risk of psoriasis. Methods: We utilized data from the National Health Insurance Research Database of Taiwan between 1996 and 2013. In total, 17,168 patients with PCa were identified; 5,141 ADT patients comprised the study group with 5,141 matched non-ADT controls. We used 1:1 propensity score-matched analysis. The demographic characteristics and comorbidities of the patients were analyzed; Cox proportional hazards regression was used to calculate the HRs for the risk of psoriasis. Results: Eighty-nine (0.87%) patients with newly diagnosed psoriasis were identified. Compared with non-ADT patients, ADT patients had similar risk of subsequent psoriasis with an HR of 0.95 (95% CI 0.63–1.45; P=0.816). However, a higher risk of psoriasis was observed in angiotensin-converting enzyme inhibitors patients (adjusted HR 2.14, 95% CI 1.09–4.20; P

Chia-Hsien Chen,1–3 Wei-Chuan Chen,4 Chun-Yi Lin,5 Chih-Hwa Chen,1–3 Yang-Hwei Tsuang,1,2 Yi-Jie Kuo2,6 1Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan; 2Department of Orthopedic Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan City, Taiwan; 5Department of Orthopedic Surgery, Taipei Medical University Hospital, Taipei, Taiwan; 6Department of Orthopedic Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Background: Estrogen deficiency is associated with musculoskeletal disorders. Sintered dicalcium pyrophosphate (SDCP) is a novel antiosteoporotic agent. In this study, we examined its use for restoration of bone quality and attenuation of disc degeneration in ovariectomy rats.Methods: Sixty female Sprague Dawley rats were randomly divided into 3 groups, namely sham group undergoing sham surgery, ovariectomy (OVX) group receiving an equivalent volume of isotonic sodium chloride solution, and OVX/SDCP group orally administered with 0.25 mg/mL SDCP. Animals were sacrificed at 3 and 6 months post ovariectomy and lumbar vertebrae and intervertebral discs were harvested. Bone mineral density, micro-computed tomography analysis, and biomechanical testing were performed to assess bone quality. Histological analysis with hematoxylin and eosin, Alcian blue, and Masson’s trichrome stain were conducted to determine disc degeneration. Immunohistochemistry and real-time PCR were carried out to measure the expressions of aggrecan, type I collagen, type II collagen, and MMP-1, MMP-3, and MMP-13.Results: SDCP improved bone quality as observed by the results of increased bone mineral density and stiffness in OVX rats. The improvement in disc degeneration induced by estrogen withdrawal was associated with reduced gene expressions of MMPs and increased production of collagen type II.Conclusion: SDCP prevents osteoporosis and ameliorates disc degeneration in OVX rats. It represents a favorable therapeutic agent for osteoporotic and osteoarthritic conditions in clinical practice. Keywords: sintered dicalcium pyrophosphate, ovariectomy, disc degeneration, matrix metalloprotease, inflammation

I-Chieh Mao,1 Ching-Yeh Lin,2 Chia-Lin Wu,3,4 Chew-Teng Kor,5,6 Chia-Chu Chang3,7–9 1Division of Critical Care, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 2Division of Hematology and Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 3Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 4Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 5Internal Medicine Research Center, Changhua Christian Hospital, Changhua, Taiwan; 6Graduate Institute of Statistics and Information Science, National Changhua University of Education, Changhua, Taiwan; 7Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan; 8School of Medicine, Chung-Shan Medical University, Taichung, Taiwan; 9Department of Nutrition, Hungkuang University, Taichung, Taiwan Background: Hydroxychloroquine (HCQ), one of the disease-modifying antirheumatic drugs, may lead to an inhibition of autophagy. Autophagy, an intracellular self-defense mechanism for the lysosomal degradation of cytoplasmic components such as damaged organelles, plays a role in protecting against neoplasm growth but is also vital for cancer cells due to an increased intracellular metabolic waste. Methods: Taiwan National Health Insurance Database was subjected to analysis to investigate the effect of HCQ exposure on cancer risk in patients with autoimmune diseases. Cancer incidence between patients with or without at least 12-month HCQ use was compared by propensity score-matched landmark analysis. A total of 100,000 participants were enrolled, including 7,662 patients who were diagnosed with autoimmune diseases between January 1, 2000, and December 31, 2012. Results: After propensity score matching, HCQ user and nonuser groups consist of 1,933 patients with a mean follow-up time of 7.82 and 6.7 years, respectively. During the follow-up period, 93 HCQ users and 77 HCQ nonusers developed cancers. Meanwhile, Kaplan–Meier estimates showed no difference in the overall incidence of cancer between HCQ users and nonusers. Conclusion: This propensity score-matched study of Taiwanese patients with autoimmune diseases suggested that HCQ exposure did not increase the cancer risk. Keywords: hydroxychloroquine, autophagy, cancer, autoimmune diseases, propensity score

Yong-hong Pan, Lin Jiao, Cai-yu Lin, Cong-hua Lu, Li Li, Heng-yi Chen, Yu-bo Wang, Yong He Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China Aim: Although EGFR tyrosine kinase inhibitors (TKIs) have shown dramatic effects against sensitizing EGFR mutations in non-small cell lung cancer (NSCLC), ~20%–30% of NSCLC patients with EGFR-sensitive mutation exhibit intrinsic resistance to EGFR-TKIs. The purpose of the current study was to investigate the enhanced antitumor effect of metformin (Met), a biguanide drug, in combination with gefitinib (Gef) in primary resistant human lung cancer cells and the associated molecular mechanism.Experimental design: H1975 cell line was treated with Met and/or Gef to examine the inhibition of cell growth and potential mechanism of action by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Ki67 incorporation assay, flow cytometry analysis, small interfering RNA technology, Western blot analysis and xenograft implantation.Results: Insulin-like growth factor-1 receptor (IGF-1R) signaling pathway was markedly activated in EGFR-TKI primary resistant H1975 cells as compared to EGFR-TKI acquired resistance cells (PC-9GR, H1650-M3) and EGFR-TKI sensitivity cells (PC-9, HCC827). Inhibition of IGF-1R activity by AG-1024 (a small molecule of IGF-1R inhibitor), as well as downregulation of IGF-1R by siRNA, significantly enhanced the ability of Gef to suppress proliferation and induce apoptosis in H1975 cells via the inhibition of AKT activation and subsequent upregulation of Bcl-2-interacting mediator of cell death (BIM). Interestingly, the observation showed that Met combined with Gef treatment had similar tumor growth suppression effects in comparison with the addition of AG-1024 to therapy with Gef. A clear synergistic antiproliferative interaction between Met and Gef was observed with a combination index (CI) value of 0.65. Notably, IGF-1R silencing mediated by RNA interference (RNAi) attenuated anticancer effects of Met without obviously resensitizing H1975 cells to Gef. Finally, Met-based combinatorial therapy effectively blocked tumor growth in the xenograft with TKI primary resistant lung cancer cells.Conclusion: Our findings demonstrated that Met combined with Gef would be a promising strategy to overcome EGFR-TKI primary resistance via suppressing IGF-1R signaling pathway in NSCLC. Keywords: metformin, gefitinib, IGF-1R, primary resistance, lung cancer

Meng-Heng Hsieh,1,2,* Chun-Yu Lin,1–3,* Chen-Yu Wang,2 Yueh-Fu Fang,1–3 Yu-Lun Lo,1,2 Shu-Min Lin,1,2 Horng-Chyuan Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Pulmonary and Critical Care, Saint Paul’s Hospital, Taoyuan, Taiwan *These authors contributed equally to this work Purpose: Pseudomonas aeruginosa is associated with pulmonary function decline and high disease severity in non-cystic fibrosis (CF) bronchiectasis. The prevalence of nontuberculous mycobacteria (NTM) in non-CF bronchiectasis patients has increased recently. This study investigated the impact of NTM with or without P. aeruginosa isolates in non-CF bronchiectasis patients.Patients and methods: Our retrospective study included 96 non-CF bronchiectasis patients from January 2005 to December 2014. We recorded the presentation, exacerbations, emergency department (ED) visits, hospitalization, serial pulmonary function, radiologic studies, and sputum culture results. All patients were followed up for at least 2 years.Results: The 96 patients were divided into four groups: patients with concomitant negative NTM and P. aeruginosa isolates (n=41; group 1), patients with positive NTM isolates (n=20; group 2), patients with positive P. aeruginosa isolates (n=20; group 3), and patients with concomitant positive NTM and P. aeruginosa isolates (n=15; group 4). Compared with group 1 patients, patients in groups 2 and 3 showed a significant decline in forced expiratory volume in 1 second (FEV1). They also had more frequent annual acute exacerbations (AE), ED visits, and hospitalization. Group 4 patients had the greatest FEV1 and forced vital capacity (FVC) decline and the most frequent AE, ED visits, and hospitalization.Conclusion: Concomitant NTM and P. aeruginosa isolates in non-CF bronchiectasis are associated with the greatest pulmonary function decline and the worst disease severity. This result suggested that early recognition and prompt treatment of concomitant NTM and P. aeruginosa isolates may improve the outcome in non-CF bronchiectasis patients. Keywords: nontuberculous mycobacteria, Pseudomonas aeruginosa, non-cystic fibrosis bronchiectasis

Jun Ma,1,* Yunfei He,1,2,* Xilin Liu,1,* Weiming Chen,3 An Wang,1,4 Chia-Ying Lin,5,6 Xiumei Mo,3 Xiaojian Ye1 1Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 2Department of Spinal Surgery, Lanzhou General Hospital of Lanzhou Military Command Region, Lanzhou, 3College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 4Department of Orthopaedics, Shanghai Armed Police Force Hospital, Shanghai, China; 5Structural Tissue Evaluation and Engineering Laboratories, Department of Biomedical Engineering, 6Department of Orthopaedic Surgery, University of Cincinnati, Cincinnati, OH, USA *These authors contributed equally to this work Introduction: Herniation of the nucleus pulposus (NP) because of defects in the annulus fibrosus (AF) is a well-known cause of low back pain. Defects in the AF thus remain a surgical challenge, and efforts have been made to develop new techniques for closure and repair. In this study, we developed an electrospun aligned nanoyarn scaffold (AYS) and nanoyarn/three-dimensional porous nanofibrous hybrid scaffold (HS) for AF tissue engineering. Methods: The AYS was fabricated via conjugated electrospinning, while the aligned nanofibrous scaffold (AFS) was prepared by traditional electrospinning as a baseline scaffold. The HS was constructed by freeze-drying and cross-linking methods. Scanning electron microscopy and mechanical measurement were used to characterize the properties of these scaffolds. Bone marrow derived mesenchymal stem cells (BMSCs) were seeded on scaffolds, and cell proliferation was determined by CCK-8 assay, while cell infiltration and differentiation were assessed by histological measurement and quantitative real-time polymerase chain reaction, respectively.Results: Morphological measurements showed that AYS presented a relatively better three-dimensional structure with larger pore sizes, higher porosity, and better fibers’ alignment compared to AFS. Mechanical testing demonstrated that the tensile property of AFS and AYS was qualitatively similar to the native AF tissue, albeit to a lesser extent. When BMSCs were seeded and cultured on these scaffolds, the number of cells cultured on HS and AYS was found to be significantly higher than that on AFS and culture plate after 7 days of culture (P0.05). BMSCs seeded on AYS demonstrated an increased expression of COL1A1, while the expression levels of SOX-9, COL2A1, and Aggrecan were higher in HS compared to other scaffolds (P

Tzu-Lin Yeh,1 Pei-Ching Shih,1 Shu-Jung Liu,2 Chao-Hsu Lin,3 Jui-Ming Liu,4,5 Wei-Te Lei,3,* Chien-Yu Lin3,* 1Department of Family Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, 2Department of Medical Library, MacKay Memorial Hospital, Tamsui Branch, New Taipei City, 3Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, 4Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 5Department of Medicine, National Yang-Ming University, Taipei, Taiwan *These authors contributed equally to this work Background: Influenza infection is a common disease with a huge disease burden. Influenza vaccination has been widely used, but concerns regarding vaccine efficacy exist, especially in the elderly. Probiotics are live microorganisms with immunomodulatory effects and may enhance the immune responses to influenza vaccination. Methods: We conducted a systematic review and meta-analysis to determine the influence of prebiotics/probiotics/synbiotics supplementation on vaccine responses to influenza vaccination. Studies were systematically identified from electronic databases up to July 2017. Information regarding study population, influenza vaccination, components of supplements, and immune responses were extracted and analyzed. Twelve studies, investigating a total of 688 participants, were included in this review. Results: Patients with prebiotics/probiotics supplements were found to have higher influenza hemagglutination inhibition antibody titers after vaccination (for A/H1N1, 42.89 vs 35.76, mean difference =7.14, 95% CI =2.73, 11.55, P=0.002; for A/H3N2, 105.4 vs 88.25, mean difference =17.19, 95% CI =3.39, 30.99, P=0.01; for B strain, 34.87 vs 30.73, mean difference =4.17, 95% CI =0.37, 7.96, P=0.03).Conclusion: Supplementation with prebiotics or probiotics may enhance the influenza hemagglutination inhibition antibody titers in all A/H1N1, A/H3N2, and B strains (20%, 19.5%, and 13.6% increases, respectively). Concomitant prebiotics or probiotics supplementation with influenza vaccination may hold great promise for improving vaccine efficacy. However, high heterogeneity was observed and further studies are warranted. Keywords: influenza, influenza vaccine, probiotics, prebiotics, synbiotics, antibody titer, immune response

Jui-Ming Liu,1–3,* Ren-Jun Hsu,3–5,* Fung-Wei Chang,6 Feng-Hsiang Chiu,7,8 Chia-Lun Yeh,1 Chun-Fa Huang,9,10 Shu-Ting Chang,11 Hung-Chang Lee,12 Hsin Chi,12,13 Chien-Yu Lin14,15 1Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 2Department of Medicine, National Yang-Ming University, 3Graduate Institute of Life Sciences, 4Department of Pathology and Graduate Institute of Pathology and Parasitology, the Tri-Service General Hospital, National Defense Medical Center, 5Biobank Management Center of the Tri-Service General Hospital, 6Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 7Department of Emergency Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 8Superintendent office, Lihuili Eastern Hospital, Ningbo, Zhejiang province, People’s Republic of China; 9School of Chinese Medicine, College of Chinese Medicine, China Medical University, 10Department of Nursing, College of Medical and Health Science, Asia University, Taichung City, 11Department of Gastroenterology, BinKun Women’s and Children’s Hospital, Taoyuan City, 12Department of Infectious Disease, MacKay Children’s Hospital, Taipei, 13Department of Medicine, MacKay Medical College, New Taipei city, 14Department of Pediatrics and Infectious Disease, Hsinchu MacKay Memorial Hospital, Hsinchu City, Taiwan; 15Division of Infection and Pathway Medicine, College of Medicine and Veterinary Medicine, The University of Edinburgh, Scotland, UK *These authors contributed equally to this work Objectives: Scabies is a common and annoying disorder. Pernicious anemia (PA) is a serious disease which, when untreated, leads to death. Mounting evidence suggests that immune-mediated inflammatory processes play a role in the pathophysiology of both diseases. The relationship between these two diseases has not been investigated. We conducted this study to explore the potential relationship between scabies and PA.Materials and methods: This nationwide, population-based study was conducted using the National Health Insurance Research Database of Taiwan. In total, 5,407 patients with scabies were identified as a study group and 20,089 matched patients were randomly selected as a control group. We tracked patients in both groups for a 7-year period to identify the incidence of PA. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazards regression was used to calculate the hazard ratios for PA.Results: Of the 25,496 patients in this study, 183 (0.7%) patients with newly diagnosed PA were identified during the 7-year follow-up period; 71 of 5,407 (1.3%) from the scabies group and 112 of 20,089 (0.6%) from the control group. Patients with scabies had a higher risk of subsequent PA, with a crude hazard ratio of 2.368. After adjusting for covariates, the adjusted hazard ratio was 1.51 (95% confidence interval: 1.09–2.08).Conclusion: This study demonstrated an increased risk of PA (adjusted hazard ratio 1.51) among patients with scabies. Immune-mediated inflammatory processes may contribute to this association. Further studies are warranted to investigate the entire pathological mechanisms between these two diseases. Physicians should pay attention to patients with history of scabies presented with anemia. Further confirmative tests of PA may contribute to correct diagnosis and initiation of vitamin B12 supplement. Keywords: scabies, pernicious anemia, National Health Insurance Research Database, autoimmune gastritis, vitamin B12 deficiency, cobalamin

Shou-Hsuan Liu,1–3,* Chao-Yu Chen,1,* Yi-Jung Li,1,2 Hsin-Hsu Wu,1,2 Chan-Yu Lin,1 Yung-Chang Chen,1 Ming-Yang Chang,1 Hsiang-Hao Hsu,1 Cheng-Lung Ku,2,3 Ya-Chung Tian1 1Kidney Research Center, Department of Nephrology, Lin-Kou Chang Gung Memorial Hospital and Department of Medicine, 2Graduate Institute of Clinical Medical Sciences, 3Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan *These authors contributed equally to this work Purpose: C-reactive protein (CRP) is a useful biomarker for prediction of long-term outcomes in patients undergoing chronic dialysis. This observational cohort study evaluated whether the time-averaged serum high-sensitivity CRP (HS-CRP) level was a better predictor of clinical outcomes than a single HS-CRP level in patients undergoing peritoneal dialysis (PD). Patients and methods: We classified 335 patients into three tertiles according to the time-averaged serum HS-CRP level and followed up regularly from January 2010 to December 2014. Clinical outcomes such as cardiovascular events, infection episodes, newly developed malignancy, encapsulating peritoneal sclerosis (EPS), dropout (death plus conversion to hemodialysis), and mortality were assessed. Results: During a 5-year follow-up, 164 patients (49.0%) ceased PD; this included 52 patient deaths (15.5%), 100 patients (29.9%) who converted to hemodialysis, and 12 patients (3.6%) who received a kidney transplantation. The Kaplan–Meier survival analysis and log-rank test revealed a significantly worse survival accumulation in patients with high time-average HS-CRP levels. A multivariate Cox regression analysis revealed that a higher time-averaged serum HS-CRP level, older age, and the occurrence of cardiovascular events were independent mortality predictors. A higher time-averaged serum HS-CRP level, the occurrence of cardiovascular events, infection episodes, and EPS were important predictors of dropout. The receiver operating characteristic analysis verified that the value of the time-average HS-CRP level in predicting the 5-year mortality and dropout was superior to a single serum baseline HS-CRP level. Conclusion: This study shows that the time-averaged serum HS-CRP level is a better marker than a single baseline measurement in predicting the 5-year mortality and dropout in PD patients. Keywords: dropout, encapsulating peritoneal sclerosis, high sensitivity C-reactive protein, malignancy, mortality, peritoneal dialysis

Whei-Lin Pan,1,2 Pi-Lun Chen,2 Cho-Ying Lin,1,2 Yi-Chun Pan,2 Yuh-Ren Ju,1,2 Chiu-Po Chan,1,2 Robert WW Hsu2,3 1Department of Periodontics, Chang Gung Memorial Hospital, Taipei, Taiwan; 2Graduate Institute of Dental and Craniofacial Science, Chang Gung University, Taoyuan, Taiwan; 3Department of Orthopedics, Chang Gung Memorial Hospital, Taipei, Taiwan Abstract: Bisphosphonates (BPs) suppress bone resorption and increase bone strength, thus reducing the risk of fracture. Oral BPs are widely used for the prevention and treatment of osteoporosis and osteopenia. Here, we describe the case of a postmenopausal woman who took oral alendronate for >3 years for osteoporosis. The patient presented at the clinic with sharp jaw pain and swelling on the left mandible 4 months after extraction of the third molar. Clinical examinations identified an inflamed mucosal opening with pus over an area of necrotic bone. Initial images of cone beam computed tomography revealed a sequestrum at the extracted socket. The condition did not improve after 1 week of antibiotic treatment; therefore, the alendronate treatment was terminated and the patient was prescribed strontium ranelate instead. The patient gradually recovered and, at the 2-year follow-up, the site of BP-related osteonecrosis of the jaw healed completely as determined by both clinical and cone beam computed tomography measures. The bone mineral densities in the femoral neck and lumbar spine improved after 1 year, and were maintained at the 3-year follow-up. The serum C-terminal cross-linking telopeptide values also gradually increased from the initial 130 pg/mL to 320 pg/mL at the 3-year follow-up. Taken together, this case supports the use of strontium ranelate as an alternative treatment for postmenopausal women who receive long-term oral BP treatments and are at risk for serious complications of BP-related osteonecrosis of the jaw. Keywords: bisphosphonate-related osteonecrosis of the jaw, BRONJ, bisphosphonates, strontium ranelate

Yung-Chih Kuo,1 Che-Yu Lin,1 Jay-Shake Li,2 Yung-I Lou3 1Department of Chemical Engineering, 2Department of Psychology, National Chung Cheng University, Chia-Yi, 3Department of Accounting, Providence University, Taichung, Taiwan, Republic of China Abstract: Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer’s disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood–brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD. Keywords: liposome, Alzheimer’s disease, β-amyloid, neurodegeneration, blood–brain barrier, wheat germ agglutinin

Nan-Chang Chiu,1,2,* Chien-Yu Lin,3,* Hsin Chi,1 Chun-Yan Yeung,1,2 Wei-Hsin Ting,1 Wai-Tao Chan,1 Chuen-Bin Jiang,1 Sung-Tse Li,3,4 Chao-Hsu Lin,3 Hung-Chang Lee1,2 1Department of Pediatrics, MacKay Children’s Hospital, 2Department of Medicine, MacKay Junior College of Medicine, Nursing and Management, Taipei, 3Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu City, 4Department of Statistics and Information Science, Fu Jen Catholic University, New Taipei, Taiwan *These authors contributed equally to this work Purpose: The long-term impact of Helicobacter pylori infection is complex, and concerns about the need for eradication exist. We conducted this case control study to investigate the association between H. pylori infection and failure to thrive (FTT).Patients and methods: From January 2009 to December 2011, 53 children with FTT group and matched children with the same sex and age and similar socioeconomic status without FTT (control group) were enrolled. A questionnaire was administered to the parents/guardian, and a 13C-urea breath test was performed to detect H. pylori infection.Results: We found that the total prevalence of H. pylori infection was 29.2% and that there was no association between FTT and H. pylori infection (FTT group: 32%; control group: 26.4%; P=0.67). Short stature was more common in the FTT group and abdominal pain in the control group (FTT group: 37.7%; control group: 11.3%; P=0.003). In a comparison between the H. pylori-positive and -negative groups, abdominal pain (87.1% vs 64%; P=0.032) and the frequency of endoscopy (74.2% vs 32%; P

Ran Ma, Xuefang Gong, Hua Jiang, Chunyi Lin, Yuqin Chen, Xiaoming Xu, Chenting Zhang, Jian Wang, Wenju Lu, Nanshan ZhongGuangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, The 1st Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaAbstract: Skeletal muscle atrophy and dysfunction are common complications in the chronic obstructive pulmonary disease (COPD). However, the underlying molecular mechanism remains elusive. Serum response factor (SRF) is a transcription factor which is critical in myocyte differentiation and growth. In this study, we established a mouse COPD model induced by cigarette smoking (CS) exposure for 24 weeks, with apparent pathophysiological changes, including increased airway resistance, enlarged alveoli, and skeletal muscle atrophy. Levels of upstream regulators of SRF, striated muscle activator of Rho signaling (STARS), and ras homolog gene family, member A (RhoA) were decreased in quadriceps muscle of COPD mice. Meanwhile, the nucleic location of SRF was diminished along with its cytoplasmic accumulation. There was a downregulation of the target muscle-specific gene, Igf1. These results suggest that the CS is one of the major cause for COPD pathogenesis, which induces the COPD-associated skeletal muscle atrophy which is closely related to decreasing SRF nucleic translocation, consequently downregulating the SRF target genes involved in muscle growth and nutrition. The STARS/RhoA signaling pathway might contribute to this course by impacting SRF subcellular distribution. Keywords: SRF, chronic obstructive pulmonary disease, skeletal muscle atrophy, cigarette smoking

Ma R, Gong XF, Jiang H, et al. Reduced nuclear translocation of serum response factor is associated with skeletal muscle atrophy in a cigarette smoke-induced mouse model of COPD. International Journal of COPD. 2017;12:581–587. On page 583, left column, last paragraph, the primer for the Igf1 gene forward: 5′-tgctgtccctctatgcttcc-3′, reverse: 5′-gaaggaatagccacgctcag-3′ should be forward: 5′-tggatgctcttcagttcgtg-3′, reverse: 5′-cacaatgcctgtctgaggtg-3′.Read the original article

Chung-Yin Lin1*, Hsiao-Ching Tseng1*, Heng-Ruei Shiu1, Ming-Fang Wu2, Cheng-Ying Chou3, Win-Li Lin1,41Institute of Biomedical Engineering, 2Laboratory Animal Center, 3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan; 4Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan*These authors contributed equally to this workAbstract: Ultrasound (US) sonication with microbubbles (MBs) has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD) on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage) with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage) with PLD 6 (or 4) mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue) injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1) US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2) for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3) with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4) for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg), the tumor size still increased for several days and then decreased (a biphasic pattern); (5) MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood vessels and enhances the delivery of PLD into tumors to significantly inhibit tumor growth.Keywords: ultrasound, microbubbles, nanodrug, mouse tumor, vascular disruption, tumor growth response

Understanding the fine interplay between spin and orbital degrees of freedom in the surface states of topological insulators is the key to the development of next-generation spintronics devices. So far, the majority of studies have focused on the helical spin texture of the topologically protected surface state (TSS) and little attention has been devoted to the spin texture of the other surface states: the bulk-originated quantum well states (QWSs). This paper presents such study in a prototypical topological insulator, Bi2Se3. By using spin- and angle-resolved photoemission spectroscopy, we reveal a full momentum-dependent spin texture of the QWSs and their response to light polarization. We find that these states share a similar spin-orbital texture with the TSS. This paper shows an intimate correlation between the surface and bulk states, which was overseen before, and provides relevant information to understand how the surface states evolve with the bulk states.

The periodontal probe is the gold standard tool for periodontal examinations, including probing depth measurements, but is limited by systematic and random errors. Here, we used photoacoustic ultrasound for high-spatial resolution imaging of probing depths. Specific contrast from dental pockets was achieved with food-grade cuttlefish ink as a contrast medium. Here, 39 porcine teeth (12 teeth with artificially deeper pockets) were treated with the contrast agent, and the probing depths were measured with novel photoacoustic imaging and a Williams periodontal probe. There were statistically significant differences between the 2 measurement approaches for distal, lingual, and buccal sites but not mesial. Bland-Altman analysis revealed that all bias values were < ±0.25 mm, and the coefficients of variation for 5 replicates were