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1. Association between alopecia areata and retinal diseases: A nationwide population-based cohort study

Author: Mu Hong Chen, Tzeng Ji Chen, Ying-Xiu Dai, Y.T. Chang, Sheng-Hsiang Ma, Hui-Chu Ting, and Ying-Hsuan Tai
Subjects: Retinal Vascular Occlusion, medicine.medical_specialty, Alopecia Areata, business.industry, Proportional hazards model, Incidence, Hazard ratio, Taiwan, Retinal, Retrospective cohort study, Dermatology, Disease, Alopecia areata, medicine.disease, Cohort Studies, chemistry.chemical_compound, Retinal Diseases, chemistry, Risk Factors, Internal medicine, medicine, Humans, business, Retrospective Studies, Retinopathy
Abstract: Background Growing evidence has revealed abnormalities in the retinal structure of patients with alopecia areata (AA). However, the relationship between AA and retinopathy remains unclear. Objective To investigate the association between AA and retinal diseases. Method The study participants were recruited from the National Health Insurance Research Database in Taiwan. We included 9,909 patients with AA and 99,090 matched controls to assess the risk of retinal diseases. A Cox regression model was used for all analyses. Results Compared with the controls, patients with AA had an adjusted hazard ratio (aHR) of 2.96 (95% confidence interval [CI], 2.20–3.98) for retinal diseases. With respect to individual retinal disease, AA patients had a significantly higher risk of developing retinal detachment (aHR, 3.80; 95% CI, 1.97–7.31), retinal vascular occlusion (aHR, 2.14; 95% CI, 1.09–4.19), and retinopathy (aHR 3.18; 95% CI 2.21–4.57) than controls. Limitations This is a retrospective cohort study. Meanwhile, almost all the participating individuals were residents of Taiwan; therefore, the validity of our findings in other demographics remains unclear. Conclusion Patients with AA had a significantly higher risk of retinal disease than the controls. Further studies are needed to clarify the pathophysiology of AA and retinal diseases.
Published: 2022

2. Stereotactic body radiotherapy plus cetuximab for previously irradiated un-resectable head and neck cancer

Author: Tai-Lin Huang, Fu-Min Fang, Yu-Tsai Lin, Hui-Ching Chuang, Chih-Yen Chien, Shau-Hsuan Li, Ming-Hsien Tsai, Chi-Chih Lai, Chao-Hui Yang, and Yan-Ye Su
Subjects: PET-CT, Cetuximab, Squamous Cell Carcinoma of Head and Neck, business.industry, Carcinoma, Head and neck cancer, General Medicine, Progressive Metabolic Disease, Radiosurgery, medicine.disease, Head and neck squamous-cell carcinoma, Metabolic Diseases, Head and Neck Neoplasms, Cyberknife, Response Evaluation Criteria in Solid Tumors, Positron Emission Tomography Computed Tomography, medicine, Humans, Neoplasm Recurrence, Local, Nuclear medicine, business, Progressive disease, medicine.drug
Abstract: Background The aim of the study was to explore the treatment outcomes and prognostic factors for patients with previously irradiated but unresectable recurrent head and neck squamous cell carcinoma (rHNSCC) treated by stereotactic body radiotherapy (SBRT) plus cetuximab at a single institute in Taiwan. Methods From February 2016 to March 2019, 74 patients with previously irradiated but unresectable rHNSCC were treated with SBRT plus cetuximab. All patients received irradiation to the gross tumor and/or nodal area with 40-50 Gy in five fractions, with each fraction interval ≥ 2 days over a 2-week period by using the CyberKnife M6 machine. An18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan was performed before treatment for treatment target delineation (n = 74) and 2 months later for response evaluation (n = 60). The median follow-up time was 9 months (range 1-36 months). Results The treatment response rate was complete response: 25.0%, partial response: 41.7%, stable disease: 11.7%, and progressive disease: 21.7% based on the criteria of the Response Evaluation Criteria in Solid Tumors (n = 72) and complete metabolic response: 21.7%, partial metabolic response: 51.7%, stable metabolic disease: 13.3%, and progressive metabolic disease: 13.3% based on PET-CT (n = 60), respectively. The 1-/2-year overall survival (OS) and progression-free survival (PFS) rates were 42.8%/22.0% and 40.5%/19.0%, respectively. In the logistic regression model, a re-irradiation interval > 12 months was observed to be the only significant prognostic factor for a favorable treatment response. In the Cox proportional hazards model, a re-irradiation interval > 12 months and gross tumor volume (GTV) ≦ 50 ml were favorable prognostic factors of OS and PFS. Conclusion SBRT plus cetuximab provides a promising salvage strategy for those patients with previously irradiated but unresectable rHNSCC, especially those with a re-irradiation interval > 12 months or GTV ≦ 50 ml.
Published: 2022

3. Safe Zones for Percutaneous Carpal Tunnel Release

Author: Po-Ting Wu, Chung-Jung Shao, Kuo-Chen Wu, Tai-Chang Chern, Li-Chieh Kuo, I-Ming Jou, and Tung-Tai Wu
Subjects: medicine.medical_specialty, Percutaneous, business.industry, medicine.disease, Carpal Tunnel Syndrome, Surgery, Carpal tunnel release, Humans, Medicine, Orthopedics and Sports Medicine, Intraoperative Complications, business, Carpal tunnel syndrome, Ultrasonography, Interventional
Abstract: Carpal tunnel release (CTR) is an effective procedure used in open, endoscopic, or ultrasound-guided methods. The complications are rare but potentially devasting. Most complications come from errors related to intraoperative technique, especially in the minimally invasive approach. An understanding of the "safe zones" is essential to perform percutaneous CTR safely. This article reviews the anatomy of safe zones and the ultrasound-guided CTR (UCTR) techniques in an attempt to prevent intraoperative complications. In strict accordance with the concepts of safe zones, UCTR is an effective and reliable procedure. Substantial experience for ultrasound-guided injection and surgery is required.
Published: 2022

4. Routine HIV Testing and Outcomes: A Population-Based Cohort Study in Taiwan

Author: Shu-Sen Chang, Ming-Chieh Shih, Chi-Tai Fang, Yu-Yao Lee, Kuan-Yin Lin, Yi-Hsuan Chen, Zong-Tai Wu, and Chang-Hsun Chen
Subjects: Pediatrics, medicine.medical_specialty, Epidemiology, Transmission (medicine), business.industry, Hazard ratio, Public Health, Environmental and Occupational Health, MEDLINE, Early detection, Hiv testing, medicine.disease, Individual risk, Population based cohort, Acquired immunodeficiency syndrome (AIDS), medicine, business
Abstract: INTRODUCTION Routine HIV testing is expected to facilitate early diagnosis and treatment. Nevertheless, to date, limited data are available on the presumed benefit of early detection with improved outcomes through routine HIV testing. METHODS This study was based on the Taiwan national HIV/AIDS registry, with follow-up data validated through December 31, 2014. Outcomes of people diagnosed with HIV infection through the routine (routinely offered in specific settings, opt-out) versus through nonroutine (individual risk-based) testing were compared. The main outcomes of the study were late diagnosis, HIV-related mortality, and all-cause mortality. Individuals were matched by year of HIV diagnosis and adjusted for age, sex, transmission routes, and SES. Analyses were conducted in 2019-2020. RESULTS This study included all 28,674 people diagnosed with HIV infection during 1986-2014 (8,431 [29%] by routine testing, 18,305 [64%] by individual risk-based testing) with a mean follow-up time of 6.2 years. Routine testing was associated with an 80% lower likelihood of late HIV diagnosis (AOR=0.20, 95% CI=0.18, 0.23, p
Published: 2022

5. Clinical Efficacy of Cerebrolysin and Cerebrolysin plus Nootropics in the Treatment of Patients with Acute Ischemic Stroke in Vietnam

Author: Luc Tran, X. Anton Alvarez, Hoang-Anh Le, Dat-Anh Nguyen, Thinh Le, Ngoc Nguyen, Thang Nguyen, Tai Nguyen, Tan Vo, Tuan Tran, Chinh Duong, Huyen Nguyen, Sam Nguyen, Hien Nguyen, Thanh Le, and Minh Nguyen
Subjects: Male, medicine.medical_specialty, Brain Ischemia, chemistry.chemical_compound, Pharmacotherapy, Pregnancy, Internal medicine, Clinical endpoint, medicine, Humans, Prospective Studies, Clinical efficacy, Amino Acids, Adverse effect, Stroke, Acute ischemic stroke, Nootropic Agents, Ischemic Stroke, Pharmacology, business.industry, General Neuroscience, medicine.disease, Neuroprotective Agents, Treatment Outcome, Vietnam, chemistry, Cerebrolysin, Combined therapy, Female, business
Abstract: Aims: To investigate the efficacy and safety of Cerebrolysin and Cerebrolysin plus nootropics in the routine treatment of patients with acute ischemic stroke (AIS). Background: Acute ischemic stroke (AIS) is a leading cause of disability with unmet treatment needs lacking effective drug therapy. Multimodal drugs modulating stroke pathophysiology as Cerebrolysin constitute a good therapeutic option. Objective: In this study, we assessed the effects of Cerebrolysin and Cerebrolysin plus nootropics, in comparison with other nootropic drugs alone, on functional, neurological and cognitive recovery of patients with AIS in Vietnam. Methods.: This non-interventional, controlled, open-label, prospective and multicenter study included 398 AIS patients (234 males) treated with Cerebrolysin (n=190; 20 i.v. infusions of 10 ml), other nootropics (comparator group; n=86), or a combination of both (n=122). The study primary endpoint was the modified Ranking Scale (mRS) score on day 90. Secondary endpoints included study-period change in NIHSS score; percentage of well-recovered (mRS 0-2) patients, the proportion of good NIHSS response (≥6 points) cases, and MoCA scores at day 90; and safety indicators. Results: Compared with other nootropics, both Cerebrolysin and combined therapy induced significant improvements (p11) cases only. No drug-related adverse events were reported. Conclusion: Cerebrolysin alone or combined with other nootropics was effective and safe in routine AIS treatment, during both acute and recovery phases, which supports its use in daily clinical practice. Other: According to the results of this multicenter study, the importance of reducing differences in the treatment regimens of AIS in Vietnam should be further emphasized.
Published: 2022

6. Perceptions of Infertility Risk Among Chinese Parents of Children with Cancer: A Qualitative Study

Author: Ho Yu Cheng, Teddy Tai Ning Lam, Samantha Lai-Ka Lee, Ho Cheung Chau, Chi Kong Li, Alex Wing Kwan Leung, Yin Ting Cheung, Lok Sum Yang, Nelson C. Y. Yeung, and Cedric Ka Chun Cheung
Subjects: Adult, Parents, Infertility, China, media_common.quotation_subject, Young Adult, Neoplasms, Perception, medicine, Humans, Fertility preservation, Young adult, Child, media_common, business.industry, Collectivism, Cancer, medicine.disease, Infertility risk, Fertility, Oncology, Pediatrics, Perinatology and Child Health, business, Qualitative research, Clinical psychology
Abstract: Objective: Anticancer treatment may be associated with damage to the reproductive organs and risk of infertility in children with cancer. The collectivist cultural norms of Asian societies may lead...
Published: 2022

7. Status epilepticus secondary to hyperammonaemia: a late presentation of an undiagnosed urea cycle defect

Author: Gabriela Nerone, Penelope Beddoes, and Charlotte Tai
Subjects: Adult, Pediatrics, medicine.medical_specialty, Encephalopathy, Case Report, Status epilepticus, Organic disease, Late presentation, 03 medical and health sciences, 0302 clinical medicine, Status Epilepticus, medicine, Humans, Hyperammonemia, Urea, In patient, 030212 general & internal medicine, Child, Ornithine transcarbamylase deficiency, business.industry, Valproic Acid, General Medicine, medicine.disease, Ornithine Carbamoyltransferase Deficiency Disease, Schizophrenia, Urea cycle, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: In this report, we describe the diagnosis, investigation and management of a patient presenting with refractory status epilepticus secondary to a previously unrecognised urea cycle defect, ornithine transcarbamylase deficiency, causing a hyperammonaemic encephalopathy. While metabolic disorders will be readily considered in a paediatric population presenting with difficult seizures, it is unusual for such cases to present in adulthood, and maintaining a broad differential in patients with status epilepticus is important. Early recognition and initiation of treatment are vital. Furthermore, the patient had been diagnosed with schizophrenia over a decade previously and more recently started on sodium valproate, a medication known to contribute to hyperammonaemia. This case also emphasises the importance of exclusion of underlying organic disease prior to diagnosis of psychiatric conditions.
Published: 2023

8. Laparoscopic versus open resection for rectal cancer: An individual patient data meta analysis of randomized controlled trials

Author: Jieling Xiao, Neng Wei Wong, Brendan J. Moran, Nicholas Syn, Wen Hui Lim, Darren Jun Hao Tan, Yip Han Chin, Zachariah Gene Wing Ow, Tianyuan Gu, Choon Seng Chong, Bee Choo Tai, Cheng Han Ng, Fung Joon Foo, and Andrew C. Lynch
Subjects: Laparoscopic surgery, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Disease-Free Survival, law.invention, Randomized controlled trial, law, Open Resection, medicine, Humans, Stage (cooking), Randomized Controlled Trials as Topic, Proctectomy, Rectal Neoplasms, business.industry, Proportional hazards model, Hazard ratio, General Medicine, medicine.disease, Surgery, Treatment Outcome, Oncology, Meta-analysis, Laparoscopy, business
Abstract: Background and aims The role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. Methods Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results Seven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78–1.06, p = 0.241) and 0.86 (95% CI:0.73–1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54–0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55–0.99, p = 0.041). Conclusions This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.
Published: 2022

9. Serum cytokine/chemokine profiles predict hepatitis B reactivation in HBV/HCV co-infected subjects receiving direct-acting antiviral agents

Author: Jia-Horng Kao, Tai-Chung Tseng, Hung-Chih Yang, Tung-Hung Su, Pin-Nan Cheng, Pei-Jer Chen, Chun-Jen Liu, Shang-Chin Huang, and Chen-Hua Liu
Subjects: Hepatitis B virus, medicine.medical_specialty, Chemokine, Hepacivirus, CCL2, Antiviral Agents, Gastroenterology, Internal medicine, medicine, Humans, Interferon gamma, biology, Coinfection, Tumor Necrosis Factor-alpha, business.industry, virus diseases, General Medicine, Hepatitis C, Chronic, Hepatitis B, medicine.disease, Hepatitis C, Normal limit, digestive system diseases, Serum cytokine, biology.protein, Cytokines, Virus Activation, Tumor necrosis factor alpha, Chemokines, business, Direct acting, medicine.drug
Abstract: BACKGROUND/PURPOSE Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting. METHODS From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation). RESULTS There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P
Published: 2022

10. Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Author: Graeme J. Hankey, Maree L. Hackett, Osvaldo P. Almeida, Leon Flicker, Gillian E. Mead, Martin S. Dennis, Christopher Etherton-Beer, Andrew H. Ford, Laurent Billot, Stephen Jan, Thomas Lung, Erik Lundström, Katharina S. Sunnerhagen, Craig S. Anderson, Huy Thang-Nguyen, John Gommans, Qilong Yi, Veronica Murray, Robert Herbert, Gregory Carter, Geoffrey A. Donnan, Huy-Thang Nguyen, Qiang Li, Severine Bompoint, Sarah Barrett, Anne Claxton, Julia O’Dea, Michelle Tang, Clare Williams, Shenae Peterson, Christie Drummond, Uyen-Ha Hong, Linh-Thi My Le, Tram-Thi Bich Ngo, Yen-Bao Mai, Huyen-Thanh Han, Nhu-Quynh Truong, Huong-Thi Nguyen, Hai-Thanh Ngo, Thi Binh Nguyen, Oanh-Thi Kieu Ha, Trang-Le Huyen Nguyen, Richard I. Lindley, Peter New, Andrew Lee, Thanh-Trung Tran, Loan-Tran Truc Mai Le, Thuy-Le Vu Kieu, Sang-Van Nguyen, Thuy-Anh Diem Nguyen, Tam-Nhat Dang, Hanh-Thi Truc Phan, Loan-Thi Ngoc Vo, Mai-Hue Nguyen, Hanh-Cao Dang, Hong-Thi Tran, Linh-Thi Cam Dam, Trinh-Thi Kim Ngo, Thai-Nguyen Thanh Pham, Binh-Nguyen Pham, Nha-Thi Thanh Dao, Huong-Thi Bich Nguyen, Linh-Thi Cam Le, Chi-Minh Do, Huy-Quoc Huynh, Giau-Thi Kim Tran, Oanh-Thi Le, Ly-Thi Khanh Tran, Chinh-Dinh Duong, Duong-Van Kieu, Na Le, Hoa-Ngoc Nguyen, Binh-Van Le, Long-Thanh Nguyen, Long-Van Nguyen, Tuan-Quoc Dinh, Tan-Van Vo, Tram-Ngoc Bui, Uyen-Thi To Hoang, Hien-Thi Bich Nguyen, Ha-Thi Thu Nguyen, Nga-Thuy Lam, Khanh-Kim Le, Phuong-Thanh Trinh, Hop-Quang Huynh, Thao-Thi Thu Nguyen, Huyen-Ngoc Lu, Tham-Hong Pham, Sam-Hoanh Nguyen, Ninh-Hong Le, Giang-Truong Nguyen, Bich-Thi Doan, Sung-Phuoc Pham, Duong-Huu Luong, Ha-Van Mai, Thuc-Van Tran, Phuong-Thi Do, Hoai-Thi Le, Chi-Van Nguyen, Phuong-Doan Nguyen, Ton-Duy Mai, Phuong-Viet Dao, Dung-Tien Nguyen, Dai-Quoc Khuong, Trung-Xuan Vuong, Lan-Tuong Vu, Ngoc-Duc Ngo, Hanh-Hong Dang, Phuong-Thai Truong, Ngan-Thi Le, Hoa-Van Hoang, Chung-Quang Do, Minh-Thao Nguyen, Anh-Hai Dam, Quynh-Nhu Le, Ngoc-Hoang Nguyen, Tuyen-Van Nguyen, Toan-Dinh Le, Ha-Thi Hai Dinh, Cuong–Van Pham, Khanh-Thi Ngoc Thach, Linh-Hai Nguyen, Loan-Thi Nguyen, Vien-Chi Le, Phuong-Hong Tran, Tai-Anh Nguyen, Tuan-Van Le, Luyen-Van Truong, Tue-Chau Bui, Ngoc-Xuan Huynh, Lap-Van Dinh, An-Gia Pham, Trang-Thi Huyen Le, Vy-Tuong Nguyen, Yen-Hai Nguyen, Thang-Ba Nguyen, Huy Thai, Quyen-Thi Ngoc Pham, Khoa-Duy Dao, Quoc-Nguyen Bao Pham, Thuong-Thi Huyen Dang, Huong-Huynh To Dinh, Trang-Mai Tong, Thuy-Thi Vu, Si-Tri Le, Tai-Ngoc Tran, Phuong-Hoai Tran, Ngoc-Thuy Nhu Dinh, Binh-Thanh Nguyen, Vinh-Phuong Do, Anh-Ngoc Nguyen, Binh-Thi Thanh Nguyen, David Blacker, Lindsey Bunce, Ai Ling Tan, Darshan Ghia, Gillian Edmonds, Nicole O’Loughlin, Megan Ewing, Kerri-Ann Whittaker, Lorralee Deane, Yash Gawarikar, Brett Jones, Maria Lopez, Koushik Nagesh, Emma Siracusa, Stephen Davis, Amy McDonald, Jess Tsoleridis, Rachael McCoy, David Jackson, Gab Silver, Timothy R. Bates, Amanda Boudville, Lynda Southwell, Dennis Cordato, Alan J. McDougall, Cecilia Cappelen-Smith, Zeljka Calic, Shabeel Askar, Qi Cheng, Raymond Kumar, Richard Geraghty, Maree Duroux, Megan Ratcliffe, Samantha Shone, Cassandra McLennan, Ramesh Sahathevan, Casey Hair, Stanley Levy, Beverley Macdonald, Benjamin Nham, Louise Rigney, Dev Nathani, Sumana Gopinath, Vishal Patel, Abul Mamun, Benjamin Trewin, Chun Phua, Ho Choong, Lauren Tarrant, Kerry Boyle, Luisa Hewitt, Monique Hourn, Amanda Masterson, Kim Oakley, Karen Ruddell, Colette Sanctuary, Kimberley Veitch, Camelia Burdusel, Lina Lee, Gary Cheuk, Jeremy Christley, Tabitha Hartwell, Craig Davenport, Kate Hickey, Rosanna Robertson, Michelle Carr, Sam Akbari, Hannah Coyle, Megan O’Neill, Cameron Redpath, Caroline Roberts, Marjan Tabesh, Toni Withiel, Kapila Abeysuriya, Andrew Granger, Angela Abraham, Chermaine Chua, Dung Do Nguyen, Vathani Surendran, Melissa Daines, David Shivlal, Mudassar Latif, Noreen Mughal, Patricia Morgan, Martin Krause, Miriam Priglinger, Ehsan E. Shandiz, Susan Day, Lay Kho, Michael Pollack, Judith Dunne, Helen Baines, Merridie Rees, Jenni White, Aicuratiya Withanage, Candice Delcourt, Cheryl Carcel, Alejandra Malavera, Amy Kunchok, Elizabeth Ray, Elizabeth Pepper, Emily Duckett, Sally Ormond, Andrew Moey, Timothy Kleinig, Vanessa Maxwell, Chantal Baldwin, Wilson Vallat, Deborah Field, Romesh Markus, Kirsty Page, Danielle Wheelwright, Sam Bolitho, Steven Faux, Fix Sangvatanakul, Alexis Brown, Susan Walker, Jennifer Massey, Hillary Hayes, Pesi Katrak, Annie Winker, Alessandro Zagami, Alanah Bailey, Sarah Mccormack, Andrew Murray, Mark Rollason, Christopher Taylor, Fintan O’Rourke, Ye Min Kuang, Heike Burnet, Yvonne Liu, Aileen Wu, Diana Ramirez, Tissa Wijeratne, Sherisse Celestino, Essie Low, Cynthia Chen, Jennifer Bergqvist, Andrew Evans, Queenie Leung, Martin Jude, Rachael McQueen, Katherine Mohr, Latitia Kernaghan, Paul Stockle, Boon L. Tan, Sara Laubscher, Diana Schmid, Melissa Spooner, Bhavesh Lallu, Bronwen Pepperell, John Chalissery, Karim Mahawish, Susan DeCaigney, Paula Broughton, Karen Knight, Veronica Duque, Harry McNaughton, Jeremy Lanford, Vivian Fu, and Lai-Kin Wong
Subjects: Male, medicine.medical_specialty, Steering committee, medicine.medical_treatment, Placebo, B700, Fractures, Bone, Cognition, Double-Blind Method, Recurrence, Seizures, Fluoxetine, Internal medicine, Humans, Medicine, Stroke, Fatigue, Aged, Ischemic Stroke, Acute stroke, Advanced and Specialized Nursing, business.industry, Recovery of Function, Middle Aged, Functional recovery, medicine.disease, Clinical trial, Affect, Hemorrhagic Stroke, Quality of Life, Accidental Falls, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Stroke recovery, Selective Serotonin Reuptake Inhibitors, medicine.drug
Abstract: Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.
Published: 2021

11. Serum PIVKA-II and alpha-fetoprotein at virological remission predicts hepatocellular carcinoma in chronic hepatitis B related cirrhosis

Author: Shan Han Chang, Hung-Chih Yang, Tai-Chung Tseng, Cheng Yuan Peng, Jia-Horng Kao, Pei-Jer Chen, Tung-Hung Su, Chun-Jen Liu, Chen-Hua Liu, and Chi-Ling Chen
Subjects: Liver Cirrhosis, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Gastroenterology, Hepatitis B, Chronic, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Protein Precursors, Retrospective Studies, Predictive marker, business.industry, Liver Neoplasms, Confounding, Hazard ratio, General Medicine, Middle Aged, medicine.disease, digestive system diseases, Confidence interval, ROC Curve, Hepatocellular carcinoma, Prothrombin, alpha-Fetoproteins, business, Liver cancer, Alpha-fetoprotein, Biomarkers
Abstract: Background The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). We aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy. Methods Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated. Results Overall, 293 CHB-related cirrhosis patients were included. At VR, the mean age was 55, and the mean PIVKA-II level was 35 mAU/mL. After a mean follow-up of 78 months, 76 patients developed HCC and 19 died. After adjustment for confounding factors, alpha-fetoprotein >7 ng/mL (hazard ratio [HR]: 2.84, 95% confidence interval [CI]: 1.73–4.67) and PIVKA-II >50 mAU/mL (HR: 2.46, 95%CI: 1.35–4.49) at VR significantly predicted HCC development. In patients with alpha-fetoprotein ≤10 ng/mL or ≤20 ng/mL at VR, PIVKA-II >50 mAU/mL increased 2.45 or 3.16-fold risk of HCC, respectively. PIVKA-II levels after VR increased serially in patients who developed HCC afterwards. Conclusions In patients with CHB-related cirrhosis, serum alpha-fetoprotein >7 ng/mL and PIVKA-II >50 mAU/mL at the time of antiviral therapy-induced VR is associated with a greater risk of HCC. PIVKA-II is a predictive marker for HCC in patients with low normal alpha-fetoprotein level.
Published: 2022

12. Diagnosis of Balamuthia mandrillaris Encephalitis by Thymine–Adenine Cloning Using Universal Eukaryotic Primers

Author: Seong Min Kim, Myung Jun Kim, Myung Hee Yi, Ju Yeong Kim, Joon Sup Yeom, Tai Soon Yong, and Hyun Dong Yoo
Subjects: Sanger sequencing, Cloning, Naegleria fowleri, biology, Biochemistry (medical), Clinical Biochemistry, General Medicine, Amplicon, biology.organism_classification, medicine.disease, Virology, Balamuthia mandrillaris, TA cloning, symbols.namesake, Plasmid, parasitic diseases, medicine, symbols, Encephalitis
Abstract: Background Identifying the causal pathogen of encephalitis remains a clinical challenge. A 50-year-old man without a history of neurological disease was referred to our department for the evaluation of an intracranial lesion observed on brain magnetic resonance imaging (MRI) scans, and the pathology results suggested protozoal infection. We identified the species responsible for encephalitis using thymine-adenine (TA) cloning, suitable for routine clinical practice. Methods We extracted DNA from a paraffin-embedded brain biopsy sample and performed TA cloning using two universal eukaryotic primers targeting the V4-5 and V9 regions of the 18S rRNA gene. The recombinant plasmids were extracted, and the inserted amplicons were identified by Sanger sequencing and a homology search of sequences in the National Center for Biotechnology Information Basic Local Alignment Search Tool. Results The infection was confirmed to be caused by the free-living amoeba Balamuthia mandrillaris. Two of 41 colonies recombinant with 18S V4-5 primers and 35 of 63 colonies recombinant with the 18S V9 primer contained B. mandrillaris genes; all other colonies contained human genes. Pathogen-specific PCR ruled out Entamoeba histolytica, Naegleria fowleri, Acanthamoeba spp., and Toxoplasma gondii infections. Conclusions This is the first report of B. mandrillaris-induced encephalitis in Korea based on molecular identification. TA cloning with the 18S rRNA gene is a feasible and affordable diagnostic tool for the detection of infectious agents of unknown etiology.
Published: 2022

13. COVID-2019 Pneumonia

Author: Ishaq Al Salmi, Faiza Al Kindi, Faryal Khamis, Jokha Al Kalbani, Saqar Al Tai, Rashid Al Umairi, Sachin Jose, Mohammed Al Busaidi, Atheel Kamona, and Huda Al Khalili
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Radiography, Ground-glass opacity, medicine, Humans, Lung, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, X-Rays, Mortality rate, COVID-19, Pneumonia, General Medicine, Middle Aged, medicine.disease, medicine.anatomical_structure, Radiological weapon, Female, Radiography, Thoracic, Radiology, medicine.symptom, Chest radiograph, business
Abstract: Objectives: The aim of this study is to assess the correlation between the severity of the initial chest x-ray abnormalities in patients with confirmed diagnosis of coronavirus disease 2019 (COVID-19) and the final outcomes. Methods: Retrospectively, we identified serial chest radiographs of 64 patients (57 men, 7 women, with mean age of 50 years) admitted to the Royal Hospital between March 15, 2020 and May 30, 2020 with confirmed diagnosis of COVID-19. The chest radiographs were examined for presence, extent, distribution and progression pattern of radiological abnormalities. Each lung field was divided into 3 zones on each CXR and a score was allocated for each zone. The scores (0 [normal], 1 [mild] to 4 [severe]) for all six zones per chest radiographic examination were summed to provide a cumulative chest radiographic score (range, 0–24). Results: The initial CXR was abnormal in 60 patients (93.8%). The most common finding was ground glass opacity (58/64, 90.6%), followed by consolidation (50/64, 78.1%). The majority of the patients had bilateral (51/64, 85%), multifocal (57/64 95%) combined central and peripheral (36/64, 60%) lung abnormalities. The median score of initial CXR for deceased patients was significantly higher than those who recovered (17 vs 11 respectively; P = 0.009). Five CXR evolution patterns were identified: type I (initial radiograph deteriorates then improves), type II (fluctuate), type III (static), type IV (progressive deterioration) and type V (progressive improvement). Conclusion: Higher baseline chest radiograph score is associated with higher mortality rate and poor prognosis in those with COVID-19 pneumonia. Keywords: SARS-CoV-2; COVID-19; Chest X-ray; Scoring System; Pneumonia; Prognosis; Outcome; Severity; Consolidation; Ground-glass.
Published: 2022

14. Triangular configuration with headless compression screws in the fixation of transverse patellar fracture

Author: Chih Wei Chang, Chun Ting Li, Chia Jung Chang, Hung-Chih Chang, Chih Hsien Chen, Tai-Hua Yang, and Yen Nien Chen
Subjects: musculoskeletal diseases, business.industry, Bone Screws, Patella, Knee extension, musculoskeletal system, medicine.disease, Compression (physics), Biomechanical Phenomena, Finite element simulation, Fracture Fixation, Internal, Fractures, Bone, Transverse plane, Fixation (surgical), Mechanical stability, Humans, General Earth and Planetary Sciences, Medicine, Displacement (orthopedic surgery), Patella fracture, Range of Motion, Articular, business, General Environmental Science, Biomedical engineering
Abstract: A triangular configuration with three parallel cannulated screws is an established treatment for fixing transverse patellar fractures; however, the stability achieved with this approach is slightly lower than that attained with cannulated screws combined with anterior wiring. In the present study, triangular configurations were modified by partially or totally replacing the cannulated screws with headless compression screws (HCSs). Through finite element simulation involving a model of distal femoral, patellar, and proximal tibial fractures, the mechanical stability levels of the modified triangular configurations were compared with that of two cannulated screws combined with anterior wiring. Four triangular screw configurations were developed: three HCSs in a forward and backward triangular configuration, two deep cannulated screws along with one superficial HCS, and two superficial cannulated screws with one deep HCS. Also considered were two parallel cannulated screws (inserted superficially or deeply) combined with anterior wiring. The six approaches were all examined in full knee extension and 45° flexion under physiological loading. The highest stability was obtained with the three HCSs in a backward triangular configuration, as indicated by the least fragment displacement and the smallest fracture gap size. In extension and flexion, this size was smaller than that observed under the use of two deeply placed parallel cannulated screws with anterior wiring by 50.3% (1.53 vs. 0.76 mm) and 43.2% (1.48 vs. 0.84 mm), respectively. Thus, the use of three HCSs in a backward triangular configuration is recommended for the fixation of transverse patellar fractures, especially without the use of anterior wiring.
Published: 2022

15. GLI3 Is Stabilized by SPOP Mutations and Promotes Castration Resistance via Functional Cooperation with Androgen Receptor in Prostate Cancer

Author: Chun Liang Chen, Tim H M Huang, Xiang Gu, Thu Minh Duong, Marieke Burleson, Haojie Huang, Yuqian Yan, Yi Zou, Michael A. Liss, Thomas G. Boyer, Lu-Zhe Sun, P. Renee Yew, Acarizia Easley, Addanki P. Kumar, Debodipta Das, Janice Jianhong Deng, Yi Chen, Tai Qin, and Roble Bedolla
Subjects: Male, Cancer Research, animal structures, medicine.drug_class, Nerve Tissue Proteins, SPOP, Article, Mice, Prostate cancer, Castration Resistance, Zinc Finger Protein Gli3, Cell Line, Tumor, medicine, Animals, Humans, Sonic hedgehog, Molecular Biology, biology, business.industry, Nuclear Proteins, Ubiquitin-Protein Ligase Complexes, Gene signature, Androgen, medicine.disease, Repressor Proteins, Androgen receptor, Prostatic Neoplasms, Castration-Resistant, Oncology, Receptors, Androgen, Mutation, embryonic structures, biology.protein, Cancer research, Signal transduction, business
Abstract: Although the Sonic hedgehog (SHH) signaling pathway has been implicated in promoting malignant phenotypes of prostate cancer, details on how it is activated and exerts its oncogenic role during prostate cancer development and progression is less clear. Here, we show that GLI3, a key SHH pathway effector, is transcriptionally upregulated during androgen deprivation and posttranslationally stabilized in prostate cancer cells by mutation of speckle-type POZ protein (SPOP). GLI3 is a substrate of SPOP-mediated proteasomal degradation in prostate cancer cells and prostate cancer driver mutations in SPOP abrogate GLI3 degradation. Functionally, GLI3 is necessary and sufficient for the growth and migration of androgen receptor (AR)–positive prostate cancer cells, particularly under androgen-depleted conditions. Importantly, we demonstrate that GLI3 physically interacts and functionally cooperates with AR to enrich an AR-dependent gene expression program leading to castration-resistant growth of xenografted prostate tumors. Finally, we identify an AR/GLI3 coregulated gene signature that is highly correlated with castration-resistant metastatic prostate cancer and predictive of disease recurrence. Together, these findings reveal that hyperactivated GLI3 promotes castration-resistant growth of prostate cancer and provide a rationale for therapeutic targeting of GLI3 in patients with castration-resistant prostate cancer (CRPC). Implications: We describe two clinically relevant mechanisms leading to hyperactivated GLI3 signaling and enhanced AR/GLI3 cross-talk, suggesting that GLI3-specific inhibitors might prove effective to block prostate cancer development or delay CRPC.
Published: 2022

16. Chronic Obstructive Pulmonary Disease Is Not Associated with a Poor Prognosis in COVID-19

Author: Yong Bum Park, Kyungjoo Kim, Tai Joon An, Y.O. Kim, Do Yeon Cho, Kwang-Ha Yoo, and Chin Kook Rhee
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, Univariate analysis, Poor prognosis, Coronavirus disease 2019 (COVID-19), RC705-779, business.industry, Pulmonary Infection, Odds ratio, medicine.disease, Intensive care unit, Confidence interval, law.invention, chronic obstructive pulmonary disease, Diseases of the respiratory system, Infectious Diseases, covid-19, law, Internal medicine, Linear regression, medicine, Original Article, prognosis, business
Abstract: Background: The effect of underlying chronic obstructive pulmonary disease (COPD) on coronavirus disease 2019 (COVID-19) during a pandemic is controversial. The purpose of this study was to examine the prognosis of COVID-19 according to the underlying COPD.Methods: COVID-19 patients were assessed using nationwide health insurance data. Comorbidities were evaluated using the modified Charlson Comorbidity Index (mCCI) which excluded COPD from conventional CCI scores. Baseline characteristics were assessed. Univariable and multiple logistic and linear regression analyses were performed to determine effects of variables on clinical outcomes. Ages, sex, mCCI, socioeconomic status, and underlying COPD were selected as variables.Results: COPD patients showed older age (71.3±11.6 years vs. 47.7±19.1 years, p
Published: 2022

17. Different cutoffs of hypertension, risk of incident diabetes and progression of insulin resistance: A prospective cohort study

Author: Jung-Nan Wei, Chung-Yi Yang, Jou-Wei Lin, Yenh-Chen Hsein, Lee-Ming Chuang, Shyang-Rong Shih, Wan-Chen Wu, Hung-Yuan Li, Mao-Shin Lin, Chia-Hung Lin, Kang-Chih Fan, Cyue-Huei Hua, and Chi-Tai Fang
Subjects: Medicine (General), medicine.medical_specialty, Cutoffs, Hypertension risk, 03 medical and health sciences, R5-920, 0302 clinical medicine, Insulin resistance, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Prospective Studies, Oral glucose tolerance, Risk factor, Prospective cohort study, business.industry, General Medicine, Guideline, medicine.disease, 030220 oncology & carcinogenesis, Hypertension, 030211 gastroenterology & hepatology, Insulin Resistance, business
Abstract: Background/Purpose: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance. Methods: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used. Results: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p
Published: 2022

18. Sex differences in the diagnosis of autism spectrum disorder and effects of comorbid mental retardation and attention-deficit hyperactivity disorder

Author: Yen Kuang Yang, Tzu I. Lee, Yi-Ting Hsieh, Yueh Ju Lien, Po See Chen, Mei Hung Chi, Ying Chun Tai, and Chia Hung Tang
Subjects: Male, Medicine (General), Pediatrics, medicine.medical_specialty, Population, Taiwan, Comorbidity, behavioral disciplines and activities, 03 medical and health sciences, R5-920, 0302 clinical medicine, Intellectual Disability, mental disorders, medicine, Humans, Attention deficit hyperactivity disorder, Cumulative incidence, Autism spectrum disorder, education, Sex Characteristics, education.field_of_study, Diagnosis age, business.industry, Incidence, Incidence (epidemiology), Hazard ratio, General Medicine, medicine.disease, Health insurance database, Attention Deficit Disorder with Hyperactivity, 030220 oncology & carcinogenesis, Female, Sex, 030211 gastroenterology & hepatology, business
Abstract: Background/purpose: The association between sex and diagnostic behavior of autism spectrum disorder (ASD), and the effects of comorbid mental retardation (MR) and attention-deficit hyperactivity disorder (ADHD), were explored. Methods: Based on the Taiwan Longitudinal Health Insurance Database (LHID)-2000 and data from 1996 through 2008, the cumulative incidence of ASD over time was compared between the sexes (both cohorts n = 38,117) using the log-rank test. The effects of comorbid MR and ADHD on the incidence of ASD were evaluated using Cox proportional hazard regression analysis. The age at first diagnosis of ASD in the two sexes was compared using the independent-sample t-test. Results: The incidence was higher in males than in females (0.0007 vs. 0.0002) across ages. Comorbid MR or ADHD increased the incidence of ASD in both sexes; comorbid MR or ADHD also decreased the male to female hazard ratio of ASD, with no significant differences in the incidence density of ASD between sexes. ADHD delayed diagnosis in both sexes (males: 6.61 vs 5.10, p
Published: 2022

19. Relationship of medication adherence, serum uric acid level and diet to recurrent attacks of gout

Author: Amirul A. Mohd Tajuddin, Tharsyini Sasitharan, Zhan P. Chong, Esha Dasgupta, Ke X. Voon, Keen S. Tai, Swan Sim Yeap, and Ming N. Ting
Subjects: medicine.medical_specialty, Asia, Gout, business.industry, Serum uric acid, Malaysia, Medication adherence, Mean age, RC581-607, medicine.disease, Obesity, Diet, Rheumatology, Adherence, Internal medicine, Recurrent gout attacks, Medicine, Serum uric acid level, Gouty arthritis, Immunologic diseases. Allergy, business, Body mass index
Abstract: Aim of the work To evaluate the relationship between medication adherence, serum uric acid (SUA) levels, and diet, with recurrent gout attacks. Patients and methods This study included 89 patients being followed up for gouty arthritis. A self-administered, structured questionnaire was used to collect socio-demographic data, gout attacks frequency, history of acute intake of purine rich foods prior to the gouty attack, and adherence to urate-lowering therapies (ULT). Results 89 patients were studied, 84 males and 5 females with a mean age of 55.4 ± 13.7 years, disease duration 12.22 ± 9.2 years and body mass index 24.67 ± 5.01. 71.9% were Malays, 20.2% Chinese, 6.7% Indians and 1.1% others. 61.8% had at least one episode of gout flare in the past 6 months. Of the 86 taking ULT, 65 (75.6%) were adherent. There was no difference in clinical characteristics between those who had high versus low adherence. High adherence to ULT was not associated with lower SUA or not having recurrent gout attacks. Having a high SUA level [OR = 2.86 (95%CI:1.52–5.39)], acute intake of purine-rich foods [OR = 2.01 (95%CI:1.09–3.73)] and obesity [OR = 1.58 (95%CI:1.09–2.32)] were significantly associated with recurrent gout attacks. Conclusions Although three-quarters of patients were adherent to their ULT, it was not associated with a reduction in recurrent gout attacks or lower SUA levels. Recurrent gout attacks were associated with a high SUA and an acute intake of purine-rich foods. To reduce the burden of recurrent gout attacks, ULT may need to be intensified even in adherent patients, as well as avoiding dietary indiscretions.
Published: 2022

20. Investigating DYT1 in a Taiwanese dystonia cohort

Author: Chun-Hwei Tai, Chin-Hsien Lin, Ying-Fa Chen, Pei-Lung Chen, Yung-Yee Chang, Min-Yu Lan, and Meng-Chen Wu
Subjects: Proband, Adult, Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Medicine (General), Taiwan, DYT1, Limb dystonia, TOR1A, 03 medical and health sciences, 0302 clinical medicine, R5-920, medicine, otorhinolaryngologic diseases, Humans, Cervical dystonia, Family history, Child, Dystonia, business.industry, Writer's cramp, Intrafamilial variability, Genetic Diseases, X-Linked, General Medicine, medicine.disease, Ashkenazi jews, nervous system diseases, Dystonic Disorders, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, business, Molecular Chaperones
Abstract: Background/purpose A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort. Methods We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020. Results Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04). Conclusion Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.
Published: 2022

21. Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

Author: Manabu Muto, Chikatoshi Katada, Tetsuji Yokoyama, Tomonori Yano, Ichiro Oda, Yasumasa Ezoe, Satoshi Tanabe, Yuichi Shimizu, Hisashi Doyama, Tomoyuki Koike, Kohei Takizawa, Motohiro Hirao, Hiroyuki Okada, Takashi Ogata, Atsushi Katagiri, Takenori Yamanouchi, Yasumasa Matsuo, Hirofumi Kawakubo, Tai Omori, Nozomu Kobayashi, Tadakazu Shimoda, Atsushi Ochiai, Hideki Ishikawa, Kiichiro Baba, Yusuke Amanuna, Akira Yokoyama, Shinya Ohashi, Kazuhiro Kaneko, Shuko Morita, Makiko Funakoshi, Takahiro Horimatsu, Mari Takahashi, Haruhisa Suzuki, Satoshi Abiko, Kenichi Takemura, Hiroyoshi Nakanishi, Masahiro Saito, Nobuyuki Ara, Naomi Kakushima, Masaki Tanaka, Keisuke Hori, and Takashi Tsuda
Subjects: medicine.medical_specialty, Esophageal Cancer, business.industry, Risk Reduction, medicine.medical_treatment, Hazard ratio, Cessation of Alcohol Drinking, Alcohol, Field Cancerization, Esophageal cancer, medicine.disease, Gastroenterology, chemistry.chemical_compound, Quality of life, chemistry, Internal medicine, Medicine, Smoking cessation, Field cancerization, business, Cessation of Cigarette Smoking, Cohort study, ALDH2
Abstract: [Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.
Published: 2022

22. A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea

Author: Jae Ha Lee, Hyewon Seo, Soo-Jung Um, Chin Kook Rhee, Myung Goo Lee, Joo Hun Park, Yun Su Sim, Hyonsoo Joo, Hye Yun Park, Yong Il Hwang, Chang Hoon Lee, Eung Gu Lee, Yeon-Mok Oh, Tae Hyung Kim, Tai Joon An, Byung Keun Kim, Hyun Woo Lee, Kwang Ha Yoo, Young-Soon Yoon, Ji Ye Jung, Jin Hwa Lee, Yeonhee Park, Seung Won Ra, Jeong-Woong Park, Deog Kyeom Kim, Woo Jin Kim, Joon Young Choi, and Kyung Hoon Min
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Acute exacerbation of chronic obstructive pulmonary disease, Exacerbation, medicine.disease_cause, Virus, Diseases of the respiratory system, Internal medicine, medicine, Bacteriology, COPD, RC705-779, Pseudomonas aeruginosa, business.industry, microbiology, medicine.disease, symptom flare up, virology, respiratory tract diseases, Regimen, Infectious Diseases, medicine.anatomical_structure, Original Article, pulmonary disease, chronic obstructive, bacteriology, business, Respiratory tract
Abstract: Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea.Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed.Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016).Conclusion: Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.
Published: 2022

23. Periodontal disease and risk of mortality and kidney function decline in advanced chronic kidney disease: a nationwide population-based cohort study

Author: Hsiang Ling Wu, Yih Giun Cherng, Wan Chi Liu, Jui Tai Chen, Hsien Cheng Kuo, Ying Hsuan Tai, Mei Yi Wu, Tzeng Ji Chen, Ying Xiu Dai, and Wei Jen Chang
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Proportional hazards model, Hazard ratio, Population, 030206 dentistry, Disease, medicine.disease, End stage renal disease, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Risk of mortality, Medicine, business, education, General Dentistry, Kidney disease, Cohort study
Abstract: Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD. Taiwan’s National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest. A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49–1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75–1.10), or MACE (aHR: 1.18, 95% CI: 0.91–1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures. Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD. These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD.
Published: 2021

24. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. 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Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. 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Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , Günay Can , Ana Paula C Cândido , Felicia Cañete , Mario V Capanzana , Nadežda Capková , Eduardo Capuano , Vincenzo Capuano , Marloes Cardol , Viviane C Cardoso , Axel C Carlsson , Esteban Carmuega , Joana Carvalho , José A Casajús , Felipe F Casanueva , Ertugrul Celikcan , Laura Censi , Marvin Cervantes-Loaiza , Juraci A Cesar , Snehalatha Chamukuttan , Angelique W Chan , Queenie Chan , Himanshu K Chaturvedi , Nish Chaturvedi , Norsyamlina Che Abdul Rahim , Miao Li Chee , Chien-Jen Chen , Fangfang Chen , Huashuai Chen , Shuohua Chen , Zhengming Chen , Ching-Yu Cheng , Bahman Cheraghian , Angela Chetrit , Ekaterina Chikova-Iscener , Arnaud Chiolero , Shu-Ti Chiou , María-Dolores Chirlaque , Belong Cho , Kaare Christensen , Diego G Christofaro , Jerzy Chudek , Renata Cifkova , Michelle Cilia , Eliza Cinteza , Frank Claessens , Janine Clarke , Els Clays , Emmanuel Cohen , Hans Concin , Susana C Confortin , Cyrus Cooper , Tara C Coppinger , Eva Corpeleijn , Simona Costanzo , Dominique Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , 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Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta 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Van Schoor , Irene Gm van Valkengoed , Dirk Vanderschueren , Diego Vanuzzo , Anette Varbo , Gregorio Varela-Moreiras , Patricia Varona-Pérez , Senthil K Vasan , Tomas Vega , Toomas Veidebaum , Gustavo Velasquez-Melendez , Biruta Velika , Giovanni Veronesi , Wm Monique Verschuren , Cesar G Victora , Giovanni Viegi , Lucie Viet , Salvador Villalpando , Paolo Vineis , Jesus Vioque , Jyrki K Virtanen , Marjolein Visser , Sophie Visvikis-Siest , Bharathi Viswanathan , Mihaela Vladulescu , Tiina Vlasoff , Dorja Vocanec , Peter Vollenweider , Henry Völzke , Ari Voutilainen , Sari Voutilainen , Martine Vrijheid , Tanja Gm Vrijkotte , Alisha N Wade , Aline Wagner , Thomas Waldhör , Janette Walton , Elvis Oa Wambiya , Wan Mohamad Wan Bebakar , Wan Nazaimoon Wan Mohamud , Rildo de Souza Wanderley Júnior , Ming-Dong Wang , Ningli Wang , Qian Wang , Xiangjun Wang , Ya Xing Wang , Ying-Wei Wang , S Goya Wannamethee , Nicholas Wareham , Adelheid Weber , Niels Wedderkopp , Deepa Weerasekera , Daniel Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng 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Paola, Nauck, Matthia, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Lii, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Clae, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pagkalos, Ioanni, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Pandey, Arvind, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R, Parsaeian, Mahboubeh, Pascanu, Ionela M, Pasquet, Patrick, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Pei, Gao, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peres, Marco A, Pérez-Farinós, Napoleón, Pérez, Cynthia M, Peterkova, Valentina, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Petrauskiene, Ausra, Pettenuzzo, Emanuela, Peykari, Niloofar, Pham, Son Thai, Pichardo, Rafael N, Pierannunzio, Daniela, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N, Plans-Rubió, Pedro, Poh, Bee Koon, Pohlabeln, Hermann, Pop, Raluca M, Popovic, Stevo R, Porta, Miquel, Posch, Georg, Poudyal, Anil, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Lui, Rezaianzadeh, Abba, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021

25. Association between Coronary Artery Spasm and the risk of incident Diabetes: A Nationwide population-based Cohort Study

Author: Patrick Hu, Ming Yow Hung, Nen Chung Chang, Chun Tai Mao, Tien Hsing Chen, Chi Tai Yeh, and Ming-Jui Hung
Subjects: Adult, Male, medicine.medical_specialty, sex difference, Taiwan, Coronary Vasospasm, Type 2 diabetes, coronary artery spasm, Coronary artery disease, Young Adult, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Insulin resistance, insulin resistance, Internal medicine, Diabetes mellitus, medicine, Humans, risk factors, Risk factor, Stroke, Aged, Retrospective Studies, business.industry, Incidence, Incidence (epidemiology), Age Factors, General Medicine, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Case-Control Studies, Female, 030211 gastroenterology & hepatology, type 2 diabetes, business, Dyslipidemia, Follow-Up Studies, Research Paper
Abstract: Background: Non-diabetic coronary artery spasm (CAS) without obstructive coronary artery disease increases insulin resistance. We investigated the risk of incident type 2 diabetes (diabetes) associated with CAS. Methods: Patient records were retrospectively collected from the Taiwan National Health Insurance Research Database during the period 2000-2012. The matched cohorts consisted of 12,413 patients with CAS and 94,721 patients in the control group. Results: During the entire follow-up, the incidence of newly-diagnosed diabetes was 22.2 events per 1000 person-years in the CAS group and 13.9 events per 1000 person-years in the control group. The increased risk of CAS-related incident diabetes was observed regardless of sex and length of follow-up. The median time to incident diabetes was 2.9 and 3.5 years in the CAS and the control group (P
Published: 2021

26. Defecation induced by stimulation of sacral S2 spinal root in cats

Author: Travis Hannan, Jianan Jian, Jonathan M. Beckel, William Wang, Khari Goosby, Zhijun Shen, Christopher Chermansky, Changfeng Tai, Bing Shen, Jicheng Wang, and William C. de Groat
Subjects: Male, Contraction (grammar), Colon, Physiology, Rectum, Stimulation, Physiology (medical), Neuromodulation, medicine, Animals, Defecation, Spinal cord injury, CATS, Hepatology, business.industry, Lumbosacral Region, Gastroenterology, Balloon catheter, Anatomy, medicine.disease, Electric Stimulation, medicine.anatomical_structure, Cats, Female, Spinal Nerve Roots, business
Abstract: The aim of this study was to determine if stimulation of sacral spinal nerve roots can induce defecation in cats. In anesthetized cats, bipolar hook electrodes were placed on the S1-S3 dorsal and/or ventral roots. Stimulus pulses (1-50 Hz, 0.2 ms) were applied to an individual S1-S3 root to induce proximal/distal colon contractions and defecation. Balloon catheters were inserted into the proximal and distal colon to measure contraction pressure. Glass marbles were inserted into the rectum to demonstrate defecation by videotaping the elimination of marbles. Stimulation of the S2 ventral root at 7 Hz induced significantly (p
Published: 2021

27. Characterization of Androgen Receptor Complex Associated Protein (ARCAP) in hepatocellular carcinoma and liver

Author: Cheng-Yuan Hsia, Anna F.Y. Li, Liang-Tsai Hsiao, Wing-Yiu Lui, Tai-Jay Chang, Kuang-Tzu Huang, Gar-Yang Chau, Chia-Lin Wang, Pin-Hsing Tsaia, Yueh Chien, Kung-Liang King, and Ta-Hsien Lin
Subjects: Male, Hepatitis B virus, Cell signaling, Carcinoma, Hepatocellular, business.industry, Liver Neoplasms, General Medicine, Transfection, In situ hybridization, medicine.disease, Androgen receptor, Mice, Transactivation, Liver, Receptors, Androgen, Hepatocellular carcinoma, Cancer research, medicine, Animals, Receptor, business, Gene
Abstract: Background Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly develop general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile Male hepatitis B virus transgenic mice have greater occurrence of HCC than females. Methods We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various of expression in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/). Results The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an ARCAP (Androgen Receptor Complex Associated Protein), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP highly expresses in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP. Conclusion Our aim is to search for different types and levels of steroid receptors expressed within human hepatocellular carcinomas and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation.
Published: 2021

28. The Impacts of Obstructive Sleep Apnea Severity on Brain White Matter Integrity and Cognitive Functions in Children: A Diffusion Tensor Imaging Study

Author: Yue Liu, Tingting Ji, Yongli Guo, Ni Xin, Jie Zhang, Lin Mei, Run Si, Jiangang Liu, Yun Peng, Xiaodan Li, Jun Tai, Guifei Zhou, Jinghong Tian, Hongbin Li, Huifang Huang, Shengcai Wang, and Zhifei Xu
Subjects: medicine.medical_specialty, obstructive sleep apnoea, business.industry, Cognition, diffusion tensor imaging, medicine.disease, nervous system diseases, respiratory tract diseases, Obstructive sleep apnea, Behavioral Neuroscience, nervous system, children, Brain White Matter, Nature and Science of Sleep, Internal medicine, tract-based spatial statistics, medicine, Cardiology, business, white matter, Applied Psychology, Original Research, Diffusion MRI
Abstract: Lin Mei,1,&ast; Xiaodan Li,1,&ast; Shengcai Wang,1,&ast; Run Si,2 Tingting Ji,1 Zhifei Xu,3 Yun Peng,4 Yue Liu,4 Hongbin Li,1 Jie Zhang,1 Yongli Guo,5 Jinghong Tian,6 Guifei Zhou,2 Huifang Huang,2 Jun Tai,1,7,&ast; Jiangang Liu,8,9 Xin Ni1 1Department of Otolaryngology, Head and Surgery, Beijing Childrenâs Hospital, Capital Medical University, National Center for Childrenâs Health, Beijing, Peopleâs Republic of China; 2School of Computer and Information Technology, Beijing Jiaotong University, Beijing, Peopleâs Republic of China; 3Department of Respiration, Beijing Childrenâ²s Hospital, Capital Medical University, National Center for Childrenâ²s Health, Beijing, Peopleâs Republic of China; 4Department of Radiology, Beijing Childrenâs Hospital, Capital Medical University, National Center for Childrenâs Health, Beijing, Peopleâs Republic of China; 5Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Childrenâs Hospital, Capital Medical University, National Center for Childrenâs Health (NCCH), Beijing, Peopleâs Republic of China; 6Department of Neurorehabilitation, Beijing Childrenâs Hospital, Capital Medical University, National Center for Childrenâs Health, Beijing, Peopleâs Republic of China; 7Department of Otorhinolaryngology, Childrenâs Hospital, Capital Institute of Pediatrics, Beijing, Peopleâs Republic of China; 8Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, Peopleâs Republic of China; 9Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the Peopleâs Republic of China, Beijing, Peopleâs Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiangang LiuBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, Peopleâs Republic of ChinaEmail jgliu@buaa.edu.cnXin NiDepartment of Otolaryngology, Beijing Childrenâs Hospital, Capital Medical University, National Center for Childrenâs Health, No. 56 Nanlishilu, Beijing, Peopleâs Republic of ChinaTel +86-139-1011-1999Email nixin@bch.com.cnObjective: To investigate the impacts of obstructive sleep apnea (OSA) on white matter (WM) integrity and cognitive functions of pediatric patients with different levels of OSA severity.Methods: Fifty-eight children with OSA and thirty-four healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) examination, polysomnography (PSG), and neurocognitive assessments. Patients were divided into mild OSA (MG) and moderate-severe OSA (SG) groups. WM integrity, PSG data, and neurocognitive assessment scores were compared among those groups.Results: For apnea hypopnea index (AHI), obstructive apnea hypopnea index (OAHI), arousal index, SpO2 nadir, and attention, SG was worse than both MG and HC with MG worse than HC. For baseline SpO2 and intelligence, SG was worse than both MG and HC with no significant difference between MG and HC. Impaired WM integrity was observed in bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, right superior longitudinal fasciculus, right hippocampus, left cingulate gyrus, right uncinate fasciculus, callosum forceps major, and callosum forceps minor only for SG than for HC. WM integrity was significantly correlated with OSA severity and neurocognitive assessment scores only for SG, but not for MG.Conclusion: Decreased baseline SpO2, WM impairment, and intelligence decline were all observed only for SG, but not for MG, implying an associated relationship among decreased SpO2, WM impairment and WM impairment. Thus, for SG, additional assessments of brain damage and cognitive function decline are needed for prognostic evaluation of OSA.Keywords: diffusion tensor imaging, obstructive sleep apnoea, children, tract-based spatial statistics, white matter
Published: 2021

29. Angiopoietin-2 is associated with metabolic syndrome in chronic kidney disease

Author: Chih-Kang Chiang, Yung-Ming Chen, Jia-Sin Liu, Ming-Ching Lee, Fan-Chi Chang, Tai-Shuan Lai, Wen-Chih Chiang, and Tzong-Shinn Chu
Subjects: Medicine (General), medicine.medical_specialty, Population, Renal function, Gastroenterology, Angiopoietin-2, 03 medical and health sciences, chemistry.chemical_compound, R5-920, 0302 clinical medicine, Interquartile range, Chronic kidney disease, Internal medicine, medicine, Humans, Endothelial dysfunction, Prospective Studies, Renal Insufficiency, Chronic, education, Subclinical infection, Inflammation, Metabolic Syndrome, education.field_of_study, business.industry, Type 2 Diabetes Mellitus, General Medicine, medicine.disease, Diabetes Mellitus, Type 2, chemistry, 030220 oncology & carcinogenesis, Uric acid, 030211 gastroenterology & hepatology, Metabolic syndrome, business, Glomerular Filtration Rate, Kidney disease
Abstract: Backgrounds: Metabolic syndrome is a subclinical status in promoting atherosclerotic cardiovascular disease and type 2 diabetes mellitus. The significance of metabolic syndrome and pathophysiology in chronic kidney disease is not investigated. Methods: We enrolled adult patients with CKD stages 3 to 5 from December 2006 to December 2007. Metabolic syndrome was defined by the US National Cholesterol Education Programme Adult Treatment Panel III guidelines. Plasma levels of angiogenic growth factors were measured. Univariate and multivariate logistic regression analyses were used. Results: Total 451 patients were analyzed with median estimated glomerular filtration rate of 27.0 ml/min per 1.73m2 (interquartile range 14.3–41.3). Patients with metabolic syndrome were older (P = 0.002), had higher percentage using diuretics (P = 0.002) but lower percentage using pentoxifylline (P = 0.017). Patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein (P < 0.0001), uric acid (P = 0.009) and angiopoietin-2 (P = 0.001). Multivariate logistic regression analyses revealed significant association between plasma levels of angiopoietin-2 and metabolic syndrome (P = 0.042). Conclusion: The prevalence of metabolic syndrome in advanced CKD was higher than general population. CKD patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein, uric acid and angiopoietin-2. Plasma levels of angiopoietin-2 were significantly associated with metabolic syndrome in patients with CKD. Metabolic syndrome in CKD may be not only a prognostic factor but also an interventional target, possibly through ameliorating inflammation. Prospective and interventional studies are necessary to establish the pathophysiology.
Published: 2021

30. Higher serum homocysteine level and frequency of hyperhomocysteinemia in carcinoembryonic antigen-positive or squamous cell carcinoma-antigen-positive oral leukoplakia patients

Author: Yu-Hsueh Wu, Ping-Yi Lin, Yang-Che Wu, Ying-Tai Jin, and Ju-Hsuan Yang
Subjects: Erythrocyte Indices, medicine.medical_specialty, Hyperhomocysteinemia, Medicine (General), Iron, Gastroenterology, 03 medical and health sciences, Hemoglobins, 0302 clinical medicine, Carcinoembryonic antigen, Folic Acid, R5-920, Parietal Cells, Gastric, Antigens, Neoplasm, Internal medicine, Oral leukoplakia patient, Medicine, Humans, Vitamin B12, Hematinic, Homocysteine, neoplasms, Serpins, Autoantibodies, Squamous cell carcinoma-antigen, medicine.diagnostic_test, biology, business.industry, Folic acid deficiency, Complete blood count, General Medicine, medicine.disease, Oral leukoplakia, Carcinoembryonic Antigen Positive, Vitamin B 12, stomatognathic diseases, 030220 oncology & carcinogenesis, Serum iron, biology.protein, 030211 gastroenterology & hepatology, Leukoplakia, Oral, business
Abstract: Background/purpose Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC–Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. Methods The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. Results We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). Conclusion CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.
Published: 2021

31. Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): a single arm, single centre, phase 2 trial

Author: Sze Huey Tan, George Boon-Bee Goh, Chee Kian Tham, Neslihan A. Kaya, Justina Yick Ching Lam, Chung Yip Chan, Richard Lo, Han Chong Toh, David Tai, Weiwei Zhai, Matthew C.H. Ng, David S.W. Ng, Si Lin Koo, Brian K. P. Goh, Hui Shan Chong, Nanda Venkatanarasimha, Tony Kiat-Hon Lim, Tiffany Hennedige, Choon Hua Thng, Joycelyn Lee, Alexander Y. F. Chung, Hian Liang Huang, Apoorva Gogna, Joe Yeong, Su Pin Choo, F. Irani, Pierce K. H. Chow, Jia Qi Lim, Chow Wei Too, and Kelvin Siu Hoong Loke
Subjects: Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Population, Severity of Illness Index, Gastroenterology, Internal medicine, Ascites, Maculopapular rash, medicine, Clinical endpoint, Humans, Yttrium Radioisotopes, Chemoembolization, Therapeutic, Adverse effect, education, Immune Checkpoint Inhibitors, Aged, Singapore, education.field_of_study, Hepatology, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Combined Modality Therapy, Embolization, Therapeutic, Microspheres, Progression-Free Survival, Nivolumab, Treatment Outcome, Hepatocellular carcinoma, Administration, Intravenous, Female, Safety, medicine.symptom, business
Abstract: Summary Background Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma. Methods Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov , NCT03033446 and has been completed. Findings 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4–48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3–4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites). Interpretation Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread. Funding National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex.
Published: 2021

32. Understanding longevity in Hong Kong: a comparative study with long-living, high-income countries

Author: Jian Shi, Majid Ezzati, Sai Yin Ho, Xiaoxin I Yao, Francis P Flores, Mathew S C Chow, Vladimir Canudas-Romo, Gabriel M. Leung, C. Mary Schooling, Michael Y. Ni, Alan D. Lopez, and Tai Hing Lam
Subjects: business.industry, Diseases of poverty, media_common.quotation_subject, Public Health, Environmental and Occupational Health, Longevity, Population health, Census, medicine.disease, Life expectancy, Medicine, Prosperity, Diseases of affluence, business, High income countries, Demography, media_common
Abstract: Summary Background Since 2013, Hong Kong has sustained the world's highest life expectancy at birth—a key indicator of population health. The reasons behind this achievement remain poorly understood but are of great relevance to both rapidly developing and high-income regions. Here, we aim to compare factors behind Hong Kong's survival advantage over long-living, high-income countries. Methods Life expectancy data from 1960–2020 were obtained for 18 high-income countries in the Organisation for Economic Co-operation and Development from the Human Mortality Database and for Hong Kong from Hong Kong's Census and Statistics Department. Causes of death data from 1950–2016 were obtained from WHO's Mortality Database. We used truncated cross-sectional average length of life (TCAL) to identify the contributions to survival differences based on 263 million deaths overall. As smoking is the leading cause of premature death, we also compared smoking-attributable mortality between Hong Kong and the high-income countries. Findings From 1979–2016, Hong Kong accumulated a substantial survival advantage over high-income countries, with a difference of 1·86 years (95% CI 1·83–1·89) for males and 2·50 years (2·47–2·53) for females. As mortality from infectious diseases declined, the main contributors to Hong Kong's survival advantage were lower mortality from cardiovascular diseases for both males (TCAL difference 1·22 years, 95% CI 1·21–1·23) and females (1·19 years, 1·18–1·21), cancer for females (0·47 years, 0·45–0·48), and transport accidents for males (0·27 years, 0·27–0·28). Among high-income populations, Hong Kong recorded the lowest cardiovascular mortality and one of the lowest cancer mortalities in women. These findings were underpinned by the lowest absolute smoking-attributable mortality in high-income regions (39·7 per 100 000 in 2016, 95% CI 34·4–45·0). Reduced smoking-attributable mortality contributed to 50·5% (0·94 years, 0·93–0·95) of Hong Kong's survival advantage over males in high-income countries and 34·8% (0·87 years, 0·87–0·88) of it in females. Interpretation Hong Kong's leading longevity is the result of fewer diseases of poverty while suppressing the diseases of affluence. A unique combination of economic prosperity and low levels of smoking with development contributed to this achievement. As such, it offers a framework that could be replicated through deliberate policies in developing and developed populations globally. Funding Early Career Scheme (RGC ECS Grant #27602415), Research Grants Council, University Grants Committee of Hong Kong.
Published: 2021

33. IGF1–PI3K-induced physiological cardiac hypertrophy: Implications for new heart failure therapies, biomarkers, and predicting cardiotoxicity

Author: Celeste M.K. Tai, Sebastian Bass-Stringer, and Julie R. McMullen
Subjects: Drug, medicine.medical_specialty, Heart growth, media_common.quotation_subject, Cardiomegaly, Mice, Transgenic, Physical Therapy, Sports Therapy and Rehabilitation, Review, Disease, PI3K, Mice, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Medicine, Orthopedics and Sports Medicine, 030212 general & internal medicine, Insulin-Like Growth Factor I, Intensive care medicine, Exercise, PI3K/AKT/mTOR pathway, Cause of death, media_common, Heart Failure, Cardiotoxicity, business.industry, IGF1, 030229 sport sciences, medicine.disease, Cardiac protection, Therapies, Heart failure, Cardiac hypertrophy, GV557-1198.995, Sports medicine, Phosphatidylinositol 3-Kinase, business, RC1200-1245, Biomarkers, Sports, Signal Transduction
Abstract: Highlights • The IGF1–PI3K pathway mediates exercise induced heart growth and protection. • Strategies to mimic the benefits of exercise on the heart are of substantial interest. • Characterizing animal models of altered cardiac PI3K activity can identify new drug targets for heart disease, and biomarkers which distinguish the healthy and diseased heart. • Therapies that increase PI3K activity may provide a promising approach to improve function in the failing heart. • Systemic therapies that reduce PI3K activity, such as some cancer agents, may lead to cardiotoxicity., Heart failure represents the end point of a variety of cardiovascular diseases. It is a growing health burden and a leading cause of death worldwide. To date, limited treatment options exist for the treatment of heart failure, but exercise has been well-established as one of the few safe and effective interventions, leading to improved outcomes in patients. However, a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure. The insulin-like growth factor 1 (IGF1)–phosphoinositide 3-kinase (PI3K) pathway has been recognized as perhaps the most critical pathway for mediating exercised-induced heart growth and protection. Here, we discuss how modulating activity of the IGF1–PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart. We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure. We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity. Finally, we discuss the use of animal models of cardiac health and disease, and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.
Published: 2021

34. Subtypes of Histopathologically Classical Aldosterone-Producing Adenomas Yield Various Transcriptomic Signaling and Outcomes

Author: Yung-Ming Chen, Hsuan Liu, Vin-Cent Wu, Yu-Ping Kuo, Tai-Shuan Lai, Jeff S Chueh, Bertrand Chin-Ming Tan, Yen-Hung Lin, Taipai, and Kang-Yung Peng
Subjects: Adult, Male, medicine.medical_specialty, Gastroenterology, Transcriptome, chemistry.chemical_compound, Primary aldosteronism, Internal medicine, Adrenal Glands, Hyperaldosteronism, Internal Medicine, Humans, Medicine, In patient, Aldosterone, business.industry, Adrenal gland, Middle Aged, medicine.disease, Adrenal Cortex Neoplasms, medicine.anatomical_structure, chemistry, Yield (chemistry), Adrenocortical Adenoma, Female, business
Abstract: There have been no reports of outcome differences between distinctive subgroups in patients with unilateral primary aldosteronism with histopathologically classical adenomas. The characteristics and incidence of complete clinical success in the patients with unilateral primary aldosteronism could be associated with the concomitant existence of multiple aldosterone-producing micronodules/nodules. Altogether, 74 classical adenomas (mean, 52.9 years and 40 men [54.1%]) were identified among 98 operated patients with unilateral primary aldosteronism. Among them accompanying multiple aldosterone-producing micronodules/nodules (group A) were identified in 38 (51.3%) of the adrenal glands; these patients showed lower likelihood (42.1%) to achieve complete clinical success than that (80.6%) of those with aldosterone-producing adenoma/nodules alone (group B, P =0.001). Additionally, group A adenomas were associated with less complete clinical success (odds ratio, 5.53, P =0.005) in the multivariable regression analysis. Group A patients also had higher baseline aldosterone production (absolute aldosterone ratio) from the contralateral adrenal gland ( P =0.039). Based on the patterns of genes with highly differential expressions as uncovered by RNA-seq analysis, Group A adenomas showed distinct transcriptomic profiles in comparison to the gene expressions from Group B adenomas. Pathway enrichment analysis revealed that HTR2B-mediated calcium pathway, in terms of HTR2B , and PLCE1 was prominently downregulated in Group A adenomas. There was 51.3% of the patients with unilateral primary aldosteronism with classical group A adenomas. These patients were more likely to have hypertension-persistence after adrenalectomy. The functional signatures of Group A adenomas showed attenuated HTR2B-mediated PLC/IP3/Ca2 + pathway; this may provide some mechanistic explanation to various clinical outcomes.
Published: 2021

35. A multifaceted approach in promoting positive mental health culture in Hong Kong secondary schools: The Mindshift educational networking programme

Author: Kit Wa Chan, Yuk Yu Vinci Chan, Kai Tai Chan, Yu Hai Eric Chen, Sai Yu Simon Lui, Oi Bun Christina Lam, Yi Nam Suen, Ho Ming Edwin Lee, Tak Hing Michael Wong, Hoi Ying Lam, Wing Chung Chang, Lai Ming Christy Hui, and Ming Yin Stephanie Wong
Subjects: Government, Medical education, Schools, Adolescent, Social Stigma, education, Psychological intervention, Stigma (botany), Mental illness, medicine.disease, Mental health, Psychiatry and Mental health, Mental Health, Mood, medicine, Hong Kong, Humans, Capstone, Positive psychology, Pshychiatric Mental Health, Students, Psychology, Biological Psychiatry
Abstract: Aim Many young people with mental health problems refuse to seek help because of stigma and leave the problem untreated. Previous research suggests that contact interventions with education could improve the stigma of mental illness in young people, thereby encouraging help-seeking in distress. The current study examined the effectiveness of a multifaceted programme, the Mindshift educational networking programme (MENP), in promoting a positive mental health culture in Hong Kong secondary schools. Methods The MENP provided activities at school, teacher and student levels to 14 Hong Kong secondary schools. School activities included visits, mental health talks and support for capstone projects. While teachers participated in workshops and regional seminars, students received ambassador training workshops, contact opportunities with people with psychosis and attachment programmes. The impact of MENP was evaluated by changes in students' knowledge, attitudes and behaviours toward people with psychosis and mental illness before and after the programme, as well as by teachers' feedback on the programme. Results This study analysed data from 55 students and 20 teachers. It was found that the MENP improved students' knowledge of mood symptoms (p = .03), acceptance of people with psychosis (p = .04) and intended behaviour toward people with mental illness (p = .02). The feedback of the teachers on the programme was positive. Conclusions The results support the application of the multifaceted approach to promote a positive mental health culture in schools. The findings call on the government to implement the programme in schools in Hong Kong by providing financial support to relevant organizations.
Published: 2021

36. Therapeutic effect of simultaneous intravitreal dexamethasone and aflibercept on diabetic macular edema

Author: Yi-Chang Chou, Yi-Ming Huang, Hsin-Wei Huang, Po-Chen Tseng, Yu-Chien Chung, Tai-Chi Lin, Tsui-Kang Hsu, and Chen-Yu Chao
Subjects: medicine.medical_specialty, Visual acuity, genetic structures, Combination therapy, Recombinant Fusion Proteins, Endocrinology, Diabetes and Metabolism, Visual Acuity, Angiogenesis Inhibitors, Dexamethasone, Macular Edema, Endocrinology, Diabetic macular edema, Diabetes mellitus, Ophthalmology, Internal Medicine, medicine, Humans, Glucocorticoids, Retrospective Studies, Aflibercept, Drug Implants, Diabetic Retinopathy, SARS-CoV-2, business.industry, Therapeutic effect, General Medicine, Consecutive case series, medicine.disease, eye diseases, COVID-19 Drug Treatment, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Intravitreal Injections, Original Article, sense organs, Implant, medicine.symptom, business, Tomography, Optical Coherence, medicine.drug
Abstract: Aims To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). Methods This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. Results Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p
Published: 2021

37. Which ICD‐9 codes were assigned for malignant mesothelioma in the mortality data in the United States before the ICD‐10 was introduced?

Author: Lukas Jyuhn-Hsiarn Lee, Tsung-Hsueh Lu, Shu-Yu Tai, and Jing-Yi Wu
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Surrogate measure, Incidence, Underlying cause of death, Mortality rate, Mesothelioma, Malignant, Public Health, Environmental and Occupational Health, ICD-10, medicine.disease, United States, International Classification of Diseases, Mortality data, Cause of Death, Icd 9 codes, Humans, Medicine, Mesothelioma, business, Health statistics
Abstract: Background Malignant mesothelioma (MM) is rare and fatal; survival in most cases is only about one year. Mortality rate is, therefore, a good proxy measure of incidence rate. However, the specific International Classification of Diseases (ICD) code for MM was not available until the Tenth Revision ICD (ICD-10). Little is known on which Ninth Revision ICD (ICD-9) codes were assigned for MM in the ICD-9 era. Methods We used a 1996 double-coded mortality file compiled by the National Center for Health Statistics to calculate the detection rate (DR) and confirmation rate (CR) of selected ICD-9 codes. Results Of 2386 decedents whose underlying cause of death was MM (ICD-10 code C45), the DR (deaths) of corresponding ICD-9 code was 57% (1365) for code 199 "malignant neoplasm without specification of site;" 19% (448) for code 162.9 "malignant neoplasm of trachea, bronchus, and lung, unspecified;" 13% (310) for code 163 "malignant neoplasm of pleura;" and 11% (271) for other codes. The CR (deaths) for the aforementioned three ICD-9 codes were 4.0% (1365/33,942), 0.3% (448/150,342), and 70.8% (310/438), respectively. Conclusions The three ICD-9 codes (199, 162.9, and 163) were the most commonly used codes for MM and composed nine-tenths of all MM deaths in the years before the ICD-10 was introduced. Using only ICD-9 code 163, the code most often used as the surrogate measure of MM in mortality studies in the ICD-9 era, capture may have been only 13% of all MM deaths in the US, and the estimated number of MM deaths missed in 1996 would be 2086.
Published: 2021

38. Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment

Author: Wei-Yu Kao, Tung-Hung Su, Chun-Jen Liu, Chen-Hua Liu, Meng-Kun Tsai, Chun-Chao Chang, Jia-Horng Kao, Cheng Yuan Peng, Jo-Hsuan Wu, Yu-Lueng Shih, Chin-Lin Lin, Chih-Yuan Lee, Sheng-Shun Yang, Pei-Jer Chen, and Tai-Chung Tseng
Subjects: medicine.medical_specialty, Sustained Virologic Response, Hepatitis C virus, Population, Viremia, Hepacivirus, medicine.disease_cause, Antiviral Agents, Renal Dialysis, Internal medicine, Humans, Medicine, Pharmacology (medical), In patient, education, education.field_of_study, Hepatology, business.industry, Proportional hazards model, Hazard ratio, Gastroenterology, virus diseases, Hepatitis C, Chronic, medicine.disease, Hepatitis C, Confidence interval, Reinfection, Relative risk, business
Abstract: Background Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment-induced sustained virologic response (SVR) in patients on haemodialysis. Aims To assess the risk of HCV reinfection among patients on haemodialysis with treatment-induced SVR. Methods Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct-acting antiviral (DAA)-based treatment received follow-up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12 . The low-risk general population who achieved SVR12 and who underwent the same post-SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person-years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups. Results We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post-SVR12 follow-up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24 . The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09-0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10-0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44-4.38, P = 0.57). Conclusions The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low-risk general population. HCV microelimination in this special population is feasible once universal screening and scaled-up treatment are implemented.
Published: 2021

39. The reasons for and mortality of patients unable to receive reimplantation after resection arthroplasty for chronic hip periprosthetic infection

Author: Ta-Wei Tai, Chao-Jui Chang, Yi-Chen Chen, Yu-Hsuan Lin, and Chih Wei Chang
Subjects: medicine.medical_specialty, Anemia, business.industry, medicine.medical_treatment, Mortality rate, Periprosthetic, medicine.disease, Arthroplasty, Surgery, Resection arthroplasty, Orthopedic surgery, medicine, Orthopedics and Sports Medicine, Cumulative incidence, business, Kidney disease
Abstract: Two-stage exchange arthroplasty is a feasible treatment for chronic PJI (periprosthetic joint infection) of total hip arthroplasty (THA). However, there are large numbers of patients who are unable to ultimately receive reimplantation after resection arthroplasty owing to uncontrolled infection and multiple comorbidities. The purpose of the current study was to identify patient-related risk factors and reasons for being unable to undergo revision THA. Individuals undergoing resection arthroplasty for chronic PJI treatment from 2013 to 2020 at our institution were retrospectively reviewed. A variety of patient comorbidities, laboratory data, isolated pathogens, and follow-up status were collected for analysis. A total of 84 patients (46 men and 38 women) with a 2.7 ± 2.1-year follow-up were analyzed. Thirty-eight (45.2%) patients eventually underwent revision THA, while the other 46 (54.8%) did not receive reimplantation during follow-up. The patients without receiving reimplantation had higher Charlson comorbidity index (CCI) score (3.1 ± 2.9 versus 1.2 ± 1.5; p = 0.001). Lower cumulative incidence of receiving reimplantation was observed in patients with chronic kidney disease (log-rank test, p = 0.019), anemia (p = 0.011), presence of initial fever (p = 0.030), and oxacillin-resistant strain infection (p = 0.030). The most common reasons for not receiving reimplantation were uncontrolled infection, unstable medical conditions, and death. The patients without reimplantation had a relatively higher mortality rate (log-rank test, p = 0.002). Chronic hip PJI with poor medical conditions or oxacillin-resistant strain infection decreased the chance of undergoing revision surgery. These patients had unfavourable outcomes and a higher mortality rate after resection arthroplasty.
Published: 2021

40. Pyroptosis: A possible link between obesity‐related inflammation and inflammatory diseases

Author: Yuan Huan, Sun Chao, Sun Zhuwen, Liu Yongnian, Liu Yanrong, Pan Miao, Tai Ruiqing, and Wu Qiong
Subjects: Inflammation, Programmed cell death, Inflammasomes, Physiology, business.industry, Clinical Biochemistry, Pyroptosis, Inflammasome, Cell Biology, medicine.disease, Obesity, Proinflammatory cytokine, Pathogenesis, Insulin resistance, NLR Family, Pyrin Domain-Containing 3 Protein, Immunology, medicine, Humans, medicine.symptom, business, medicine.drug
Abstract: The main manifestation of obesity is persistent low-level inflammation and insulin resistance, which is an important factor inducing or promoting other obesity-related diseases. As a proinflammatory programmed cell death, pyroptosis plays an important role, especially in the activation and regulation of the NLRP3 inflammasome pathway. Pyroptosis is associated with the pathogenesis of many chronic inflammatory diseases and is characterized by the formation of micropores in the plasma membrane and the release of a large number of proinflammatory cytokines. This article mainly introduces the main pathways and key molecules of pyroptosis and focuses on the phenomenon of pyroptosis in obesity. It is suggested that the regulation of pyroptosis-related targets may become a new potential therapy for the prevention and treatment of systemic inflammatory response caused by obesity, and we summarize the potential molecular substances that may be beneficial to obesity-related inflammatory diseases through target pyroptosis.
Published: 2021

41. Evaluating commercially available wireless cardiovascular monitors for measuring and transmitting real‐time physiological responses in children with autism

Author: Aaron J. Masino, Anushua Bhattacharya, Daniel Forsyth, Jessica Tan, Zabryna L. Atkinson-Diaz, Heather J. Nuske, Jeffrey W. Pennington, Emma Finkel, Christopher P. Bonafide, Yelena Kushleyeva, Hungtzu Tai, John D. Herrington, and Matthew S. Goodwin
Subjects: Adult, medicine.medical_specialty, Autism Spectrum Disorder, Wearable computer, Fitness Trackers, Audiology, Article, Wearable Electronic Devices, Heart Rate, Rating scale, medicine, Humans, Heart rate variability, Autistic Disorder, Child, Genetics (clinical), Wearable technology, business.industry, General Neuroscience, medicine.disease, Digital health, Psychophysiology, Autism spectrum disorder, Autism, Neurology (clinical), business
Abstract: Commercially available wearable biosensors have the potential to enhance psychophysiology research and digital health technologies for autism by enabling stress or arousal monitoring in naturalistic settings. However, such monitors may not be comfortable for children with autism due to sensory sensitivities. To determine the feasibility of wearable technology in children with autism age 8-12 years, we first selected six consumer-grade wireless cardiovascular monitors and tested them during rest and movement conditions in 23 typically developing adults. Subsequently, the best performing monitors (based on data quality robustness statistics), Polar and Mio Fuse, were evaluated in 32 children with autism and 23 typically developing children during a 2-h session, including rest and mild stress-inducing tasks. Cardiovascular data were recorded simultaneously across monitors using custom software. We administered the Comfort Rating Scales to children. Although the Polar monitor was less comfortable for children with autism than typically developing children, absolute scores demonstrated that, on average, all children found each monitor comfortable. For most children, data from the Mio Fuse (96%-100%) and Polar (83%-96%) passed quality thresholds of data robustness. Moreover, in the stress relative to rest condition, heart rate increased for the Polar, F(1,53) = 135.70, p
Published: 2021

42. Couple and family interventions for high mortality health conditions: A strategic review (2010–2019)

Author: Keeley J. Pratt, Angela L. Lamson, Alison G. Wong, Max Zubatsky, Erin M Sesemann, Jacqueline Williams-Reade, Daniel J Blocker, Jennifer Harsh Caspari, Jennifer L. Hodgson, Tai J. Mendenhall, Erika S Taylor, Matthew P. Martin, and Braden J. Brown
Subjects: Adult, Gerontology, Family therapy, Adolescent, Sociology and Political Science, Social Psychology, Heart disease, business.industry, MEDLINE, Psychological intervention, Infant, Context (language use), Disease, medicine.disease, United States, Clinical Psychology, Humans, Medicine, Marriage, Child, business, Inclusion (education), Stroke, Social Sciences (miscellaneous)
Abstract: The earliest publications in the field of marriage and family therapy introduced interventions conducted with families experiencing complex health conditions. This strategic review captures an evaluation of efficacy for 87 couple and family interventions published between 2010 and 2019 with a focus on the leading causes of mortality in the United States. These health conditions include chromosomal anomalies and accidents with infants aged 0-4 years; accidents and cancer among children aged 5-14; accidents among adolescents aged 15-24; and heart disease, cancer, accidents, chronic lower respiratory diseases, stroke, Alzheimer's disease, diabetes, influenza/pneumonia, and nephritis/nephrosis among adults 25 and older. Results support the need for greater inclusion of couples and families in assessments and interventions. The greatest chasm in efficacy research was with minoritized couples and families. Implications include ways to initiate couple and family interventions in the context of health conditions with attention given to accessibility, recruitment, retention, and evaluation.
Published: 2021

43. Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats

Author: Ernesto P. Molmenti, Santiago J. Miyara, Junichi Sasaki, Koichiro Shinozaki, Tai Yin, Muhammad Shoaib, Shuhei Eguchi, Kentaro Oka, Kei Hayashida, Daniel M Rolston, Mitsuaki Nishikimi, Motomichi Takahashi, Koichiro Homma, Tomoaki Aoki, Rishabh C. Choudhary, Ryosuke Takegawa, Lance B Becker, Tadashi Ariyoshi, Asami Matsumoto, Yusuke Endo, and Junhwan Kim
Subjects: Vascular Endothelial Growth Factor A, medicine.medical_treatment, Placebo, General Biochemistry, Genetics and Molecular Biology, medicine, Extracorporeal membrane oxygenation, Coagulopathy, Animals, Humans, Extracorporeal cardiopulmonary resuscitation, Survival rate, Mechanical ventilation, business.industry, Research, Central venous pressure, General Medicine, Oxygenation, Heart arrest, medicine.disease, Cardiopulmonary Resuscitation, Rats, Anesthesia, Medicine, business, Ischemia reperfusion injury, Hydrogen
Abstract: Background Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. Methods Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. Results The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan–Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in d-glutamine and d-glutamate metabolism. Conclusions H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia–reperfusion injury in critically ill patients who require ECMO support.
Published: 2021

44. Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer

Author: Chander Singh Digwal, Peter J. Allen, Thomas A. Neubert, Swathi Merugu, Eileen M. O'Reilly, Wanyan Wang, Lon Yin L. Chan, Vinagolu K. Rajasekhar, Suhasini Joshi, Tony Taldone, Nagavarakishore Pillarsetty, Olivera Grbovic-Huezo, Erica DaGama Gomes, Maeve A. Lowery, Srinivasa Gandu, Anna Rodina, Stephen D. Ginsberg, Gabriela Chiosis, Vlad Miclea, Elisa de Stanchina, Laura H. Tang, Palak Panchal, Chris Sander, Lisa Shrestha, Kenneth H. Yu, Chao Xu, Steven D. Leach, Hediye Erdjument-Bromage, Marissa Mattar, Pengrong Yan, Radu I Peter, John H. Healey, Adriana D. Corben, Justina Almodovar, Sahil Sharma, William R. Jarnagin, Yelena Y. Janjigian, Salma Buddaseth, Tai Wang, and Askan Gokce
Subjects: QH301-705.5, Cell, Chemical biology, Medicine (miscellaneous), Biology, Interactome, General Biochemistry, Genetics and Molecular Biology, Article, Protein–protein interaction, Epigenesis, Genetic, Mice, Neoplasms, Protein Interaction Mapping, medicine, Animals, Humans, Protein Interaction Maps, Biology (General), Genome, Cancer, Hyperconnectivity, medicine.disease, Networks and systems biology, Cancer therapeutic resistance, Signalling, medicine.anatomical_structure, Cancer cell, Heterografts, Female, General Agricultural and Biological Sciences, Neuroscience, Molecular Chaperones, Signal Transduction
Abstract: Cancer cell plasticity due to the dynamic architecture of interactome networks provides a vexing outlet for therapy evasion. Here, through chemical biology approaches for systems level exploration of protein connectivity changes applied to pancreatic cancer cell lines, patient biospecimens, and cell- and patient-derived xenografts in mice, we demonstrate interactomes can be re-engineered for vulnerability. By manipulating epichaperomes pharmacologically, we control and anticipate how thousands of proteins interact in real-time within tumours. Further, we can essentially force tumours into interactome hyperconnectivity and maximal protein-protein interaction capacity, a state whereby no rebound pathways can be deployed and where alternative signalling is supressed. This approach therefore primes interactomes to enhance vulnerability and improve treatment efficacy, enabling therapeutics with traditionally poor performance to become highly efficacious. These findings provide proof-of-principle for a paradigm to overcome drug resistance through pharmacologic manipulation of proteome-wide protein-protein interaction networks., Joshi, Gomes et al. employ a chemical modulation approach of the cellular interactome to a hyperconnectivity state and show association with the increased response of pancreatic cancer cell lines to specific drugs, including those that target the MAPK-pathways and PI3K-mTOR pathway. To achieve this, the authors employ chemical modulation of the interactome via epichaperome inhibition with the small molecule PU-H71.
Published: 2021

45. Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway

Author: Tai-Ran Sun, Yang Sun, Meili Lu, Jing Wang, Hongxin Wang, Xu-Wei Hou, and Cong Li
Subjects: 0301 basic medicine, Cardiac function curve, Cardiac fibrosis, myocardial remodeling, Pharmacology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Muscle hypertrophy, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, medicine, CaSR, calcineurin, Cardioprotection, Ginsenoside Rg1, Chemistry, Botany, medicine.disease, Calcineurin, 030104 developmental biology, Complementary and alternative medicine, 030220 oncology & carcinogenesis, QK1-989, Signal transduction, Calcium-sensing receptor, Biotechnology, Research Article
Abstract: Background Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Methods Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca2+]i, and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca2+]i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-β1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl3 could not further increase the [Ca2+]i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca2+]i and CaN signaling but had no effect on CaSR expression. Conclusion The activation of CaN pathway and the increase of [Ca2+]i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury., Graphical abstract The mechanism of cardioprotection by Ginsenoside Rg1 via downregulation of CaSR. AAC induces overload of [Ca2+]i through CaSR/IP3R pathway. The increased [Ca2+]i leads to activation of CaN signaling pathway, resulting in cardiac hypertrophy and fibrosis. Ginsenoside Rg1 inhibits cardiac hypertrophy and fibrosis through inhibiting [Ca2+]i and downregulation of CaSR, CaN and TGF-β1 signaling pathways.Image 1
Published: 2021

46. Choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain

Author: Shi-Yin Huang, Ai-Lun Lee, Lulu Huang, and Tai-Ho Hung
Subjects: Pregnancy, medicine.medical_specialty, Ileus, Clinical presentation, Vaginal delivery, Pleural effusion, business.industry, Choriocarcinoma, Obstetrics and Gynecology, Gynecology and obstetrics, medicine.disease, Surgery, embryonic structures, RG1-991, medicine, Back pain, Lower back pain, medicine.symptom, Differential diagnosis, Presentation (obstetrics), business
Abstract: Objective We present a case of choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain. Case report The patient is a 34-year-old multiparous woman with her second pregnancy, and a history of scoliosis with spinal fixation. Her first pregnancy was uneventful, with a term vaginal delivery. She was hospitalized four times due to intractable back pain from 25 to 31 weeks, and terminated at 31 weeks. The placenta was unremarkable on gross examination. Postpartum, the patient developed obstructive ileus, requiring a rectosigmoid resection. She was diagnosed with metastatic choriocarcinoma to the liver, para-aortic lymph nodes, and mesentery. A week later, she developed micro-thrombosis of all limbs, massive ascites, pleural effusion. Patient refused chemotherapy and died on post-operative Day 15. Conclusion Presentation of choriocarcinoma in pregnancy varies widely. Clinicians should consider the differential diagnosis of choriocarcinoma when faced with abnormal unexplained symptoms during pregnancy.
Published: 2021

47. Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study—An Asian Tertiary Cancer Center Experience

Author: Matthew C.H. Ng, Alvin Soon Tiong Lim, Yoon Sim Yap, Justina Yick Ching Lam, Tony Kiat Hon Lim, Chee Keong Toh, Su Pin Choo, N. Gopalakrishna Iyer, Mohamad Farid, Amanda O.L. Seet, Chow Wei Too, Rebecca Dent, Elaine Hsuen Lim, Apoorva Gogna, Angela Takano, Daniel S.W. Tan, Wan-Teck Lim, Tira Jing Ying Tan, Eng Huat Tan, Mei Kim Ang, Gek San Tan, Bien Soo Tan, Aaron Tan, Iain Beehuat Tan, Soon Thye Lim, Tse Hui Lim, David Tai, and Anders Jacobsen Skanderup
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, business.industry, MEDLINE, Cancer, medicine.disease, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Profiling (information science), Medicine, Center (algebra and category theory), Medical physics, business
Abstract: PURPOSE Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.
Published: 2021

48. Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma

Author: Jing Shui, Xiaosong Zhu, Xiang Tai, Tian Weiwei, Zhihua Wang, Ziwei Li, Xuanpeng Li, Juehua Yu, and Hongjin Wu
Subjects: endocrine system diseases, MYEOV, DDX60L, Pancreatic ductal adenocarcinoma (PDAC), Biology, QH426-470, Metastasis, Transcriptome, Cell Line, Tumor, Biomarkers, Tumor, Tumor Microenvironment, medicine, Genetics, Humans, Oncogene, Tumor microenvironment, Gene knockdown, Research, Cancer, Oncogenes, medicine.disease, CXCL2, digestive system diseases, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, Gene expression profiling, Cancer cell, Cancer research, TP248.13-248.65, Carcinoma, Pancreatic Ductal, Biotechnology
Abstract: Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Approximately 80% of patients initially diagnosed with locally advanced or metastatic disease survive only 4–11 months after diagnosis. Tremendous efforts have been made toward understanding the biology of PDAC. Results In this study, we first utilized next-generation sequencing technique and existing microarray datasets to identify significant differentially expressed genes between PDAC and non-tumor adjacent tissue. By comparing top significant survival genes in PDAC Gene Expression Profiling Interactive Analysis database and PDAC transcriptome data from patients, our integrated analysis discovered five potential central genes (i.e., MYEOV, KCNN4, FAM83A, S100A16, and DDX60L). Subsequently, we analyzed the cellular functions of the potential novel oncogenes MYEOV and DDX60L, which are highly expressed in PDAC cells. Notably, the knockdown of MYEOV and DDX60L significantly inhibited the metastasis of cancer cells and induced apoptosis. Further RNA sequencing analyses showed that massive signaling pathways, particularly the TNF signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway, were affected in siRNA-treated cancer cells. The siDDX60L and siMYEOV significantly inhibited the expression of chemokine CXCL2, which may potentially affect the tumor microenvironment in PDAC tissues. Conclusions The present findings identified the novel oncogene DDX60L, which was highly expressed in PDAC. Transcriptome profiling through siRNA knockdown of DDX60L uncovered its functional roles in the PDAC in humans.
Published: 2021

49. Risk factors for subjective cognitive decline: the CABLE study

Author: Jin-Tai Yu, Ya-Nan Ou, Hao Hu, Lan Tan, Ya-Hui Ma, Chen Wen, and Yan-Lin Bi
Subjects: medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Home Environment, Anemia, Neurosciences. Biological psychiatry. Neuropsychiatry, Pathogenesis, Disease, Neuropsychological Tests, Predictive markers, Article, Cellular and Molecular Neuroscience, Alzheimer Disease, Risk Factors, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Cognitive Dysfunction, cardiovascular diseases, Cognitive decline, Cognitive impairment, Biological Psychiatry, Aged, business.industry, Female sex, Odds ratio, medicine.disease, Psychiatry and Mental health, Anxiety, Female, medicine.symptom, business, RC321-571
Abstract: Increasing evidences supported that subjective cognitive decline (SCD) might be a potential first symptomatic manifestation of Alzheimer’s disease (AD). The rapidly growing number of SCD individuals who seek medical help and advice also makes it urgent to develop more precise strategy for SCD. Therefore, this study aimed to explore the risk factors for SCD. Logistics and linear regression models were performed to investigate 41 factors for SCD in 1165 participants without objective cognitive impairment. Cochran-Armitage trend test was used to confirm the constant trend toward higher prevalence of SCD with an increasing number of risk factors. A high overall prevalence of SCD was found in total participants (42%). Eight factors were eventually identified as risk factors for SCD, including four stable factors associated with both SCD statues and severity (older age, thyroid diseases, minimal anxiety symptoms, and day time dysfunction; odds ratio (OR) ranging from 1.74 to 2.29) as well as four suggestive factors associated with either SCD statues or severity (female sex, anemia, lack of physical exercises, and living alone; OR ranging from 1.30 to 2.29). The prevalence of SCD gradually increased with the number of risk factors clustering increased in individuals (p for trend
Published: 2021

50. Cholinesterase inhibitors for gait, balance, and fall in Parkinson disease: a meta-analysis

Author: Chien-Tai Hong, Jia-Hung Chen, and Tsai-Wei Huang
Subjects: medicine.medical_specialty, Parkinson's disease, Gait Disturbance, business.industry, STRIDE, medicine.disease, Gait, Article, law.invention, Cellular and Molecular Neuroscience, Physical medicine and rehabilitation, Neurology, Randomized controlled trial, law, Outcomes research, Meta-analysis, medicine, Dementia, Neurology (clinical), Neurology. Diseases of the nervous system, business, RC346-429, human activities, Balance (ability)
Abstract: Gait disturbance and imbalance are the major symptoms of Parkinson disease (PD), with fall being the most undesirable consequence. However, few effective evidence-based treatments are available for alleviating these symptoms and preventing falls. Cholinesterase inhibitors (ChEIs) are a well-established treatment for PD dementia with possible impacts on gait, balance, and fall reduction. The present study involved a meta-analysis of randomized controlled trials (RCTs) to investigate the effects of ChEIs on gait, balance, and fall in patients with PD. We searched for studies using the PubMed, Embase, and Web of Science databases. The major outcomes were effects on gait parameters, balance, and fall. This study was registered with PROSPERO (CRD42021254733). Five RCTs were included in the present meta-analysis. ChEIs did not significantly increase gait speed in PD patients (mean difference [MD]: 0.03 m/s, 95% confidence interval [CI]: −0.02 to 0.07, p = 0.29). However, ChEI treatment significantly decreased step or stride variability during the single task (standard MD: −0.43, 95% CI = −0.79 to −0.06, p = 0.02). Regarding fall and balance, trending but nonsignificant beneficial effects were observed with ChEI treatment. In conclusion, although ChEI treatment did not significantly improve gait speed and reduce fall, it can significantly reduce step or stride variability. Considering that gait disorder is a challenging issue in patients with PD and that ChEIs are generally tolerable, the present meta-analysis may provide more evidence for the benefit of ChEIs on PD gait disturbance as an alternative treatment consideration.
Published: 2021

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