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Cheng-Yang Hsieh,1,2,* Po-Ting Chen,3,* Shih-Chieh Shao,2,4,5 Swu-Jane Lin,6 Shu-Chen Liao,3,7 Edward Chia-Cheng Lai2,5 1Department of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan; 2School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 4Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 5Population Health Data Center, National Cheng Kung University, Tainan, Taiwan; 6Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 7Chang Gung University College of Medicine, Taoyuan, Taiwan*These authors contributed equally to this workCorrespondence: Shu-Chen Liao, Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, 222, Maijin Road, Anle District, Keelung City, 204, Taiwan, Tel +886-2-24313131, Email ermdsusan@gmail.comPurpose: To validate the International Classification of Diseases, 10th Revision (ICD-10) codes for Guillain-Barré syndrome (GBS) in Taiwan’s insurance claims database.Methods: We identified adult patients hospitalized at any Chang Gung Memorial Foundation branch hospital between January 1st, 2017, and December 31st, 2022, with ICD-10 code G61.0 in any of the five discharge diagnosis positions, indicating possible Guillain-Barré syndrome. We then validated the possible GBS diagnosis using data from electronic medical records of the identified patients, based on the diagnostic criteria established by the National Institute of Neurological Disorders and Stroke. We determined the positive predictive values (PPV) of various operational definitions, including the position (primary or other) where the code was recorded in the discharge diagnosis, nerve conduction study (NCS) claims, and / or specific GBS treatments.Results: The final validation cohort of 484 patients with ICD-10 code for GBS in the discharge diagnosis was found to include 368 true GBS patients. Identifying inpatients using only the ICD-10 code for GBS in any of the five positions for discharge diagnosis yielded a PPV of 76.0%. With more restrictive definitions (primary diagnosis only, or requiring additional claims for NCS and/or treatments), the PPV tended to increase, but with fewer true GBS patients identified. Using ICD-10 GBS code in the primary diagnosis plus NCS and treatment claims yielded the highest PPV (98.3%); however, 140 (38.0%) of the true GBS patients were missed using this definition. In contrast, using the ICD-10 GBS code in any position, plus claims for NCS, achieved a relatively good PPV (85.8%) with minimal loss of true GBS patients (13, ie, 3.5%).Conclusion: In Taiwan’s NHI claims data, identifying true GBS patients using only the ICD-10 code yielded a PPV of 76.0%; however, adding claims for diagnostic procedure and GBS treatment increased the PPV to 98.3%.Keywords: validation, positive predictive value, diagnostic codes, ICD-10, Guillain-Barré syndrome

Li-Ying Wu,1 Shih-Chieh Shao,2 Shu-Chen Liao1,3 1Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 2Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 3Chang Gung University College of Medicine, Taoyuan, TaiwanCorrespondence: Shih-Chieh Shao, Department of Pharmacy, Keelung Chang Gung Memorial Hospital, 222 Maijin Road, Keelung, Taiwan, Email scshao@cgmh.org.tw Shu-Chen Liao, Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, 222 Maijin Road, Keelung, Taiwan, Email ermdsusan@gmail.comPurpose: The validity of the diagnosis codes to identify myocarditis cases in healthcare databases research remains unclear, and this study aimed to determine the coding accuracy of myocarditis in Taiwan.Methods: We conducted a cross-sectional study based on Taiwan’s largest multi-institutional healthcare system to identify inpatients newly diagnosed with ICD-10-CM myocarditis codes at discharge between January 1st, 2017 and March 31st, 2022. We ascertained the myocarditis diagnosis by a gold standard biopsy or by review of electronic medical records, and the positive predictive values (PPV) with 95% confidence intervals (CI) of the ICD-10-CM codes for myocarditis were determined.Results: We included a total of 498 inpatients (mean age: 33.8 years old; female: 38.8%) with new myocarditis diagnosis at discharge. Codes I409 (30.1%) and I514 (45.4%) constituted the majority of myocarditis diagnostic codes in any coding position, and the overall PPV of the myocarditis codes was 73.5% (95% CI: 69.6– 77.4%). However, the highest PPV (96.6%) for myocarditis diagnosis was noted with code I409 as the primary diagnosis. We found 132 inpatients (26.5%) who were false-positive myocarditis cases, identified by the ICD-10-CM codes, and potential reasons for misclassification included other inflammation diseases (n=35, 26.5%), pre-existing heart failure (n= 25, 18.9%) and acute myocardial infarction (n=16, 12.1%).Conclusion: The PPV of ICD-10-CM codes for myocarditis in Taiwan was acceptable, but some other inflammation diseases and pre-existing heart diseases may be falsely coded as myocarditis. Our results may serve future secondary database studies as a fundamental reference on the validity of myocarditis diagnosis codes.Keywords: ICD-CM-10 codes, positive predictive value, myocarditis, multi-institutional study, Chang Gung Research Database

Shu-Chen Liao,1,2 Shih-Chieh Shao,3,4 Edward Chia-Cheng Lai,4 Swu-Jane Lin,5 Wei-I Huang,6 Cheng-Yang Hsieh4,7 1Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 2Chang Gung University College of Medicine, Taoyuan, Taiwan; 3Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 4School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 6Taiwan Drug Relief Foundation, Taipei, Taiwan; 7Department of Neurology, Tainan Sin Lau Hospital, Tainan, TaiwanCorrespondence: Cheng-Yang HsiehDepartment of Neurology, Tainan Sin Lau Hospital, 57, Section 1, Dongmen Road, East District, Tainan, 70142, TaiwanTel +886-6-274-8316, ext. 4180Fax +886-6-282-4178Email chengyanghsieh@gmail.comObjective: This study aims to determine the positive predictive value (PPV) of case definitions for cerebral venous sinus thrombosis (CVST) in Taiwan’s National Health Insurance claims database based on the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnostic codes.Study Design and Setting: Inpatient records with ICD-10-CM codes of G08, I629, I636, or I676 were retrieved from the claims data of all hospital branches of Chang Gung Medical Foundation. Manual review of the medical records and images was performed in order to ascertain the diagnosis. The PPV of various case definitions for CVST was estimated.Results: Of the 380 hospitalizations, 166 and 214 were determined to be true-positive and false-positive episodes of acute CVST, respectively. The PPV of the ICD-10-CM codes of G08, I629, I636, and I676 was 88.2%, 2.0%, 100.0%, and 91.3%, respectively. The PPV generally increased when acute CVST was defined as a primary diagnosis or as ICD-10-CM codes plus anticoagulant use. Miscoding in other conditions, tentative diagnosis, and remote episode of CVST were determined as the main reasons for false-positive diagnosis of acute CVST.Conclusion: This study determined the PPV of ICD-10-CM codes for identifying CVST, which may offer a reference for future claims-based research.Keywords: hospitalization claims data, positive predictive value, diagnostic codes, ICD-10-CM, cerebral venous sinus thrombosis, Taiwan

Shih-Cheng Liao,1,2 Wei-Lieh Huang2– 4 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Department of Psychiatry, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; 4Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Wei-Lieh HuangDepartment of Psychiatry, National Taiwan University Hospital Yunlin Branch Email weiliehhuang@gmail.comIntroduction: The Cognitions About Body and Health Questionnaire (CABAH) is a self-rating questionnaire measuring cognitions about health. The psychometric properties of its Chinese version and its performance on evaluating somatic symptom disorder (SSD) were examined in this study.Methods: After translating the CABAH into Chinese, we collected data of the CABAH and another four questionnaires (Patient Health Questionnaire-15, Health Anxiety Questionnaire, Beck Depression Inventory-II, Beck Anxiety Inventory) in 208 SSD patients and 197 healthy individuals. We used exploratory factor analysis (EFA) to explore the structure of the Chinese CABAH. Internal consistency and criterion-related validity were analyzed. An independent t-test and receiver operating characteristic (ROC) curve analysis were used to evaluate the performance of the CABAH for evaluating SSD.Results: Six factors were suggested by EFA. Five (bodily weakness, health habits, catastrophizing interpretation of specific bodily complaints, somatosensory amplification, catastrophizing interpretation of general bodily complaints) are conceptually associated with the original CABAH. The sixth factor (reverse, with three items) is different from the original construct. Cronbach’s alpha for the CABAH was 0.885. The CABAH score was moderately correlated with scores of the other four questionnaires. Scores for the whole CABAH and scores of the six factors were all significantly higher in SSD patients than in healthy individuals. The results of ROC curve analysis were as follows: area under the curve=0.700; suggested cutoff=58/59; Youden’s J=0.295.Conclusion: The reliability and validity of the Chinese CABAH were fair, although the three items in the reverse factor should be interpreted cautiously.Keywords: Cognitions About Body and Health Questionnaire, psychometric properties, bodily weakness, somatic symptom disorder

Hsi-Chung Chen,1,2 Chia-Yi Wu,3– 5 Ming-Been Lee,1,5– 7 Shih-Cheng Liao,1,5,6 Chia-Ta Chan,5,7 Chun-Ying Chen5 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 3School of Nursing, National Taiwan University College of Medicine, Taipei, Taiwan; 4Department of Nursing, National Taiwan University Hospital, Taipei, Taiwan; 5Taiwan Suicide Prevention Center, Taipei, Taiwan; 6Department of Psychiatry, National Taiwan University College of Medicine, Taipei, Taiwan; 7Department of Psychiatry, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanCorrespondence: Chia-Yi WuSchool of Nursing, National Taiwan University College of Medicine, No.1, Sec. 1, Jen-A1 Road, Taipei 100, TaiwanTel +886-2-23123456 ext. 88430Email jennycyw@ntu.edu.tw Ming-Been LeeDepartment of Psychiatry, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei 100, TaiwanTel +886-2-23123456 Ext. 66784Email mingbeen@ntu.edu.twBackground: Insomnia is closely related to psychological distress. This study aims to examine the role of age and sex in the association between various psychological distresses and insomnia symptoms.Participants and Methods: This population-based study used data provided by cumulative respondents of the annual survey of the Taiwan Suicide Prevention Center between 2006 and 2019. Potential respondents were aged ≥ 15 years and were selected by a stratified proportional randomization method according to the distribution of population size, sex, and age in different geographic areas of Taiwan. The Five-Item Brief Symptom Rating Scale was used to measure insomnia symptoms and four psychological distresses: depression, anxiety, hostility, and inferiority. The independent relationship between insomnia symptoms with depression, anxiety, hostility, and inferiority was further examined according to age and sex.Results: A total of 28,649 participants were included (women, 50.2%). The four types of psychological distress correlated differentially with insomnia symptoms. Concerning interaction effects, sex moderated the interaction effects between age with depression, anxiety, and hostility. In men, and not in women, age moderated the relationship between insomnia symptoms and all four psychological distresses. Specifically, the effect sizes of the associations between insomnia symptoms and depression, anxiety, and hostility showed an age-dependent decreasing trend in men.Conclusion: The associations between psychological distresses and insomnia symptoms varied in strength and according to age in a sex-specific manner.Keywords: insomnia symptoms, moderation effect, psychological distress, sex-specific

Many studies have examined the effectiveness of lifestyle modifications such as exercise, diet, weight loss, and stress reduction in controlling hypertension in elderly individuals, and several meta-analyses have reported that both aerobic and resistance exercise can reduce blood pressure in this population. In addition, the higher sensitivity to sodium in elderly individuals highlights the importance of restricting salt intake for blood pressure control. Low-sodium salt or potassium supplementation can help with blood pressure control in elderly individuals with hypertension. Several clinical trials have shown that both the Dietary Approaches to Stop Hypertension (DASH) and a Mediterranean diet pattern are effective in reducing blood pressure in older hypertensive patients. Although moderate alcohol consumption does not appear to negatively impact blood pressure control in older adults, blood pressure increases along with heavy alcohol intake. Some studies have indicated that coffee intake increases blood pressure in elderly hypertensive subjects, especially for those who consume more than 3 cups a day. Clinical studies have shown that weight loss through exercise and diet control is beneficial for controlling hypertension in elderly individuals. Anxiety, depression and insomnia also appear to have an impact on elderly hypertension. In this review, we discuss the effectiveness of lifestyle modifications and non-pharmacological management of these factors and their impact on hypertension in elderly individuals, and how to effectively implement them in real-world settings., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study examined the relationship between perceived social status, COVID-19-related discrimination, and sleep quality among 158 migrant care workers in Taiwan. Data were collected via computer-assisted interviews, assessing perceived social status with the MacArthur scale and sleep quality using the Pittsburgh Sleep Quality Index. The results revealed that higher perceived social status in reference to the destination country (B = 0.31) and experience of media stigmatization (B = 0.52) were associated with higher global Pittsburgh Sleep Quality Index (PSQI) scores, whereas perceived social status in reference to the home country and others forms of pandemic-related discrimination were not associated with PSQI scores. The study concluded that social comparison and stigmatization were linked to sleep health of migrant care workers. Understanding these factors can inform the development of targeted interventions to address inequalities faced by migrants., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lynch syndrome (LS) is an autosomal dominant disorder characterized by increased risks of colorectal and endometrial cancers. LS is defined by pathogenic variants in mismatch repair (MMR) genes, including MLH1, MSH2, and MSH6. Data on the prevalence and associated cancer risks of LS in the Han Chinese population remain limited. In this study, using a broad biobank approach through the Taiwan Precision Medicine Initiative (TPMI), we identified LS-associated MMR gene variants within a cohort of 42,828 participants from a Taiwanese medical center. A total of 89 individuals were found to carry pathogenic MMR variants: MLH1 (n = 22, 25%), MSH2 (n = 47, 53%), and MSH6 (n = 20, 22%). The overall prevalence of MMR variants was calculated, and cancer incidence rates among carriers were determined. The prevalence of MMR variants in the study population was 1 in 481. The distribution of MLH1, MSH2, and MSH6 variants were 24.7%, 52.8%, and 22.5%, respectively. Cumulative cancer incidence rates of carriers were 40.9% for MLH1 carriers, 29.8% for MSH2, and 40% for MSH6. Among the 19 individuals who underwent colonoscopy screening, the prevalence of polyps was similar to that of the control group (adenoma detection rate: 32% vs 26%, p = 0.585). A meticulous analysis of the detected polyps in seven participants, considering factors such as location, size, morphology, and pathological features, showed no significant differences from controls. A significant cancer risk is associated with LS-related MMR variants in the Taiwanese population. The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.

Background: Cryptococcus is an opportunistic infection acquired through inhalation from the environment, primarily affecting individuals with compromised immune systems. It typically leads to pneumonia upon passing through lung tissue. The infection can disseminate to various organs via the bloodstream, resulting in meningitis or encephalitis in the central nervous system. Disseminated Cryptococcus has been reported to involve the skin, liver, eyes, lymph nodes, bone marrow, spleen, kidneys, and intestines, significantly increasing morbidity and mortality. However, pancreatic involvement in Cryptococcus is relatively rare, and a few case reports have highlighted severe organ damage and high mortality rates., Case Presentation: In this case report, we present the case of a 36-year-old Asian man who presented with a 2-week history of headaches and blurred vision in his right eye. Brain magnetic resonance imaging revealed multiple brain masses, along with a mass in the lower left lung field and a tumor in the pancreatic tail, as detected by chest computed tomography. Endoscopic ultrasound-guided fine needle biopsy and computed tomography-guided lung biopsy confirmed the diagnosis of disseminated cryptococcal infection involving the pancreas, lung, and brain. The patient's clinical condition improved following antifungal therapy. Additionally, we identified anti-granulocyte-macrophage colony-stimulating factor antibody as a risk factor for disseminated cryptococcal infection in this patient., Conclusion: Disseminated cryptococcosis can be a potentially lethal condition, as highlighted by previous literature. However, early diagnosis using contrast-enhanced harmonic endoscopic ultrasound and endoscopic ultrasound-guided biopsies, as well as prompt treatment as demonstrated in our case, can improve outcomes and prevent mortality., (© 2024. The Author(s).)

Background and Objectives: Endoscopic ultrasound (EUS) is an imaging modality that can be applied to predict preoperative T staging. It is important for the patient to decide whether to receive endoscopic therapy, surgical intervention, or neoadjuvant therapy. The objectives of our study were to (1) identify if EUS could precisely predict T1-stage tumor, which is suitable for endoscopic treatment and (2) identify if EUS could precisely predict tumors more advanced than T3, which would mandate neoadjuvant therapy., Methods: A retrospective study of patients who received gastrectomy was conducted from March 2017 to December 2021 at Taichung Veterans General Hospital. Those who received preoperative EUS, with final pathology showing gastric adenocarcinoma were included. Consistency of EUS prediction and pathology, accuracy, and parameters impacting accuracy were analyzed., Results: The κ value was 0.6 if the T stage was not grouped, indicating moderate agreement. Overall accuracy was 52.8%. Overestimation and underestimation rates were 17.6% and 29.5%, respectively. The accuracy of T stages is highest in T1 (85.23%). The κ value of T1-stage was 0.67, and those of T2, T3, and T4 were below 0.5. Regarding parameters affecting accuracy, we found longitudinal portion, Borrmann type, ulcer presentation, early gastric cancer, and size of tumor could influence the accuracy., Conclusions: Our study showed that EUS was a good tool for precisely predicting T1-stage of gastric adenocarcinoma preoperatively. For this situation, endoscopic treatment would be enough. However, for predicting more advanced gastric adenocarcinoma, EUS should be combined with other modalities to achieve better accuracy., (© 2024 Wiley Periodicals LLC.)

Background/purpose: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) is increasing worldwide. HPV vaccines have shown efficacy in preventing diseases in both males and females. Therefore, there is a need to develop cost-effective strategies for HPV vaccines to prevent HPV-related OPC. This meta-analysis aimed to evaluate cost-effectiveness using the global mean of incremental cost-effectiveness ratios compared to the willingness-to-pay threshold and incremental net benefits (INBs) of HPV vaccination strategies between boys' extension vaccine and girls only. These recommendations will be useful for countries that have not implemented universal HPV vaccines in national programs, such as Taiwan., Materials and Methods: Studies evaluating the cost-effectiveness of HPV vaccination strategies in the prevention of OPC that included both sexes versus girls only were identified through the Cochrane Library, EMBASE, PubMed, ScienceDirect, and Web of Science databases on February 05, 2024, and a meta-analysis of pooled INBs was performed using a random-effects model. The outcome was an effective measurement of the OPC burden. The results are represented in USD (2024)., Results: Fifteen model analyses were included. All the studies were conducted in high-income countries. The global mean of incremental cost-effectiveness ratio was $39,553 (95% CI, $27,008-66,641) per quality-adjusted life years gained, which was below the global mean of the willingness-to-pay threshold of $65,473 (95% CI, $52,138-83,755). Pooled INBs of $9370 (95% CI, $5046-13,695; P  < 0.001) favored the extended HPV in boys., Conclusion: HPV vaccination strategies that include boys are cost-effective compared to those with girls only in preventing OPC burden. By implementing a universal HPV vaccination program, countries can receive $9370 in additional monetary benefits per patient. Given its relevance to high-income countries, this study offers key insights that can aid policymakers in Taiwan., Competing Interests: The authors have no conflict of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Individuals with somatic symptom disorder (SSD) often have comorbid depression or anxiety, but whether SSD is associated with specific neuropsychological functions has yet to be fully examined. We analyzed which neuropsychological features are more closely associated with SSD, anxiety, and depression. In this case-control study, we recruited 140 individuals with SSD, 104 individuals with affective disorders without SSD, and 159 healthy controls in Taiwan. We collected DSM-5 diagnoses, questionnaire scores, and performance on eight tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) for each participant. Several CANTAB tasks involving attention, executive function, and social cognition showed significant group differences. In the adjusted analysis, the tasks significantly associated with SSD were the Match to Sample Visual Search (MTS) and the Emotion Recognition Task (ERT). Among the questionnaires, the Cognitions about Body and Health Questionnaire showed the most significant associations with the tasks, specifically with Rapid Visual Information Processing, MTS, Paired Associates Learning, Spatial Working Memory, Intra-Extra Dimensional Set Shift, and ERT. We conclude that the MTS and ERT tasks show significant relationships with both SSD diagnosis and related questionnaires. These tasks primarily involve selective attention and negative emotion regulation., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Augmented reality (AR) technology involving head-mounted displays (HMD) represents a significant innovation in medical education, particularly for training in guided invasive procedures. Novice physicians often face challenges in simultaneously identifying anatomical landmarks and performing procedures when learning point-of-care ultrasound (POCUS). Our primary objective was to determine the effectiveness of AR in enhancing physician training for ultrasound-guided interventions using AR visual overlays. The secondary objective was to compare cognitive load between traditional ultrasound training settings and AR-assisted training settings., Methods: This randomized crossover study, conducted from 2021 to 2022, compared performance and cognitive load of trainees attempting accurate central venous catheter (CVC) placement using an AR-HMD to display ultrasound images (AR-US), compared with standard ultrasound without visual overlay (S-US). We enrolled 47 trainees, including 22 final-year undergraduate medical students and 25 postgraduate physicians (years 1-4) from three hospitals in Taiwan. All participants had basic training in US-guided CVC placement but lacked AR-US experience. Performance and cognitive load were assessed using time measurements and NASA Task Load Index (NASA-TLX), covering the dimensions of Mental-, Physical- and Temporal Demand, and Performance, Effort and Frustration., Results: We found AR technology reduced the time required for critical steps in CVC placement, while minimizing users' neck strain. Female and junior trainees using AR-US identified anatomy and localized veins faster than those using S-US. Using AR-US, female trainees significantly outperformed males in anatomical identification [mean difference (MD): -10.79 s (95% CI: -2.37 to -19.21)]. The NASA-TLX cognitive load assessment showed mental workload trending lower in all dimensions except performance while using AR-US, compared to S-US. Similarly, junior trainees' effort- and frustration scores were lower [MD: -2.73 (95% CI: -5.04 to -0.41) and -2.41 (95% CI: -4.51 to -0.31), respectively], as were female trainees' effort scores [MD: -3.07 (95% CI: -6.10 to -0.03)] when using AR-US, compared to S-US, whereby these differences were statistically significant., Conclusions: AR technology helped improve trainee performance and reduced cognitive load during ultrasound-guided CVC placement. These findings support the application of AR technology to enhance physician training in ultrasound-guided interventional procedures, suggesting that AR-HMDs could be a valuable tool in medical education., Trial Registration: The trial was registered with Clinicaltrials.gov on 20/09/2023 as a clinical trial, under the identifier NCT06055400., (© 2024. The Author(s).)

Background: This study aimed to estimate the population-attributable fraction (PAF) of psychiatric and physical disorders for suicide among older adults, focusing on sex- and age-specific factors., Methods: Data from Taiwan's National Health Insurance Research Data and National Death Registry included 9136 cases of suicide in individuals aged 65+, with 89,439 matched controls. Physical and psychiatric disorders were identified through diagnostic records. Conditional logistic regression assessed risk factors, and PAF was calculated using disorder prevalence and adjusted odds ratios., Results: Major suicide risk factors among older adults were depressive disorders, anxiety disorders, and sleep disorders. Physical disorders like hypertension, peptic ulcers, and cancer also showed significant PAF values. The combined PAF of physical disorders equaled that of psychiatric disorders. Psychiatric disorders had a greater impact on women and the youngest-old adults, while physical disorders had a higher contribution among men, middle-old adults, and oldest-old adults., Limitations: Relying solely on claim data to identify psychiatric and physical disorders may underestimate their prevalence and associations with suicide due to unrecorded cases of individuals not seeking help and the absence of key risk factors like social isolation and family support., Conclusions: This study identifies preventable or treatable risk factors for older adult suicide, emphasizing the need to target specific psychiatric and physical disorders in suicide prevention efforts while taking into account sex- and age-specific considerations. It also underscores the importance of establishing social welfare support systems to address the unique challenges older adults face., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mutations in the mitochondrial cristae protein CHCHD2 lead to a late-onset autosomal dominant form of Parkinson's disease (PD) which closely resembles idiopathic PD, providing the opportunity to gain new insights into the mechanisms of mitochondrial dysfunction contributing to PD. To begin to address this, we used CRISPR genome-editing to generate CHCHD2 T61I point mutant mice. CHCHD2 T61I mice had normal viability, and had only subtle motor deficits with no signs of premature dopaminergic (DA) neuron degeneration. Nonetheless, CHCHD2 T61I mice exhibited robust molecular changes in the brain including increased CHCHD2 insolubility, accumulation of CHCHD2 protein preferentially in the substantia nigra (SN), and elevated levels of α-synuclein. Metabolic analyses revealed an increase in glucose metabolism through glycolysis relative to the TCA cycle with increased respiratory exchange ratio, and immune-electron microscopy revelated disrupted mitochondria in DA neurons. Moreover, spatial genomics revealed decreased expression of mitochondrial complex I and III respiratory chain proteins, while proteomics revealed increased respiratory chain and other mitochondrial protein-protein interactions. As such, the CHCHD2 T61I point-mutation mice exhibit robust mitochondrial disruption and a consequent metabolic shift towards glycolysis. These findings thus establish CHCHD2 T61I mice as a new model for mitochondrial-based PD, and implicate disrupted respiratory chain function as a likely causative driver.

Objective: Major depressive disorder (MDD), anxiety disorders, and somatic symptom disorder (SSD) are associated with quality of life (QoL) reduction. This cross-sectional study investigated the relationship between these conditions as categorical diagnoses and related psychopathologies with QoL, recognizing their frequent overlap., Methods: We recruited a total of 403 clinical patients and healthy individuals, administering diagnostic interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. QoL and psychopathologies were assessed using the WHO Quality of Life-BREF (WHOQOL-BREF) and several self-administered questionnaires, respectively. Multiple linear regression analyses examined the associations between psychiatric diagnoses, psychopathologies, and QoL., Results: SSD and MDD were independently associated with impaired global (β = -0.318 and - 0.287) and all QoL domains (β = -0.307, -0.150, -0.125, and - 0.133, in physical, psychological, social, and environmental domains respectively for SSD; β = -0.278, -0.344, -0.275, and - 0.268 for MDD). The Beck Depression Inventory-II score showed pervasive associations with QoL (β = -0.390, -0.408, -0.685, -0.463, and - 0.420, in global, physical, psychological, social, and environmental domains). The Patient Health Questionnaire-15 and Health Anxiety Questionnaire scores were associated with global (β = -0.168 and - 0.181) and physical (β = -0.293 and - 0.121) QoL domain, while the Cognitions About Body and Health Questionnaire score was only associated with environmental QoL domain (β = -0.157)., Conclusion: SSD and MDD were independently associated with QoL impairment. Depressive symptoms were associated with all QoL domains, whereas somatic symptom burden and health anxiety primarily affected the physical QoL domain. Clinicians should consider concomitant psychopathologies when managing patients with depression, anxiety, or somatic symptoms., Competing Interests: Declaration of competing interest The authors have no competing interests to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Purpose: Capsule endoscopy (CE) is a noninvasive examination for excellent visualization of small bowel mucosal lesions. We aimed to evaluate the clinical efficacy and safety of CE in pediatric patients., Methods: From April 2014 to December 2022, CE procedures performed in children younger than 18 years of age at Taichung Veteran General Hospital were analyzed retrospectively., Results: Among 136 procedures, the completion rate was 95.6% (n = 130), with a median age of 14 years old. Suspicion or evaluation of inflammatory bowel diseases (IBD) (41%) was the most common indication for CE. Other common indications of CE were chronic unexplained abdominal pain (35%) and obscure gastrointestinal bleeding or iron deficiency anemia (21%). No procedure-related complications occurred. The diagnosis of those patients with incomplete study were CD with small bowel stricture, graft-versus-host disease and duodenal ulcers. A total of 86 CE procedures showed positive findings, and the overall diagnostic yield rate was 63.2%. Small bowel ulcers (65.12%) were the most common findings. Overall, 26.5% of CE examinations resulted in a new diagnosis and 44.9% of CE exams led to a change in therapy. For patients with IBD, CE findings resulted in an even higher therapeutic change rate of 48.1%., Conclusions: CE is a safe and feasible diagnostic method to study the small intestine in children, especially for IBD. Incomplete study could be an indicator of positive finding and can potentially be a guide to identify the site of possible strictures., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered in PD, but we understand little about if or how chronic changes in activity may contribute to degeneration. To address this question, we developed a chemogenetic (DREADD) mouse model to chronically increase DA neuron activity, and confirmed this increase using ex vivo electrophysiology. Chronic hyperactivation of DA neurons resulted in prolonged increases in locomotor activity during the light cycle and decreases during the dark cycle, consistent with chronic changes in DA release and circadian disturbances. We also observed early, preferential degeneration of SNc projections, recapitulating the PD hallmarks of selective vulnerability of SNc axons and the comparative resilience of ventral tegmental area axons. This was followed by eventual loss of midbrain DA neurons. Continuous DREADD activation resulted in a sustained increase in baseline calcium levels, supporting an important role for increased calcium in the neurodegeneration process. Finally, spatial transcriptomics from DREADD mice examining midbrain DA neurons and striatal targets, and cross-validation with human patient samples, provided insights into potential mechanisms of hyperactivity-induced toxicity and PD. Our results thus reveal the preferential vulnerability of SNc DA neurons to increased neural activity, and support a potential role for increased neural activity in driving degeneration in PD., Competing Interests: Conflict of Interest Statement The authors declare no competing interests. Anatol Kreitzer’s current role is Chief Discovery Officer at Maplight Therapeutics.

Aims: This study investigated the association between the frequency of screening for diabetic retinopathy (DR) versus the development of DR and corresponding medical expenses among patients newly diagnosed with type 2 diabetes mellitus (T2DM)., Methods: This longitudinal, population-based study used the Taiwan National Health Insurance Research Database (2004 to 2020) as a data source. Propensity score matching (PSM) (sex, age, comorbidities and concurrent medication use) was employed in the grouping of T2DM patients according to different frequency of DR screening. Outcome measures included the proportion of patients who developed DR, who received DR treatment, and the associated medical expenses and hospitalizations., Results: The 17-year cohort included 337,046 patients. After PSM, three groups each containing 35,739 patients were assembled and analyzed. Compared to low-frequency screening, high-frequency screening was more effective in detecting patients requiring treatment; however, the net cost for treatment was significantly lower. Standard-frequency screening appears to provide the best balance in terms of DR detection, diagnosis interval, the risk of DR-related hospitalization, and DR treatment costs., Conclusions: In this real-world cohort study covering all levels of the healthcare system, infrequent screening was associated with delayed diagnosis and elevated treatment costs, while a fundus screening interval of 1-2 years proved optimal in terms of detection and medical expenditures., (Copyright © 2024. Published by Elsevier Inc.)

Background: Somatic symptom disorders (SSD) and functional somatic syndromes (FSS) are often regarded as similar diagnostic constructs; however, whether they exhibit similar clinical outcomes, medical costs, and medication usage patterns has not been examined in nationwide data. Therefore, this study focused on analyzing SSD and four types of FSS (fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, functional dyspepsia)., Methods: This population-based matched cohort study utilized Taiwan's National Health Insurance (NHI) claims database to investigate the impact of SSD/FSS. The study included 2 615 477 newly diagnosed patients with SSD/FSS and matched comparisons from the NHI beneficiary registry. Healthcare utilization, mortality, medical expenditure, and medication usage were assessed as outcome measures. Statistical analysis involved Cox regression models for hazard ratios, generalized linear models for comparing differences, and adjustment for covariates., Results: All SSD/FSS showed significantly higher adjusted hazard ratios for psychiatric hospitalization and all-cause hospitalization compared to the control group. All SSD/FSS exhibited significantly higher adjusted hazard ratios for suicide, and SSD was particularly high. All-cause mortality was significantly higher in all SSD/FSS. Medical costs were significantly higher for all SSD/FSS compared to controls. The usage duration of all psychiatric medications and analgesics was significantly higher in SSD/FSS compared to the control group., Conclusion: All SSD/FSS shared similar clinical outcomes and medical costs. The high hazard ratio for suicide in SSD deserves clinical attention.

Pancreatic fluid collections (PFCs) including pancreatic pseudocyst (PP) and walled-off necrosis (WON) are complications after acute pancreatitis. We aimed to evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided lumen-apposing metal stent (LAMS) placement to manage PFCs. Between June 2019 and May 2023, patients with symptomatic PFCs who underwent EUS-guided electrocautery-enhanced LAMS drainage were enrolled retrospectively from eight tertiary centers in Taiwan. In total, 33 [14 (42.42%) PP and 19 (57.58%) WON] patients were enrolled. Gallstones (27.27%) and abdominal pain (72.73%) were the most common etiology and indication for drainage. The technical and clinical success rates were 100% and 96.97%, respectively, and the mean procedure time was 30.55 (± 16.17) min. Complications included one (3.03%) case of self-limited bleeding; there were no cases of mortality. Seven (21.21%) patients had recurrence. Patients with disconnected pancreatic duct syndrome (DPDS) had a higher recurrence rate than those without (71.43% vs. 38.46%, p = 0.05). After replacing LAMSs with transmural double-pigtail plastic stents (DPSs) in the DPDS patients, the DPS migration rate was higher in the patients with recurrence (100% vs. 33.33%, p = 0.04). In conclusion, drainage of symptomatic PFCs with EUS-guided electrocautery-enhanced LAMS appears to be efficient and safe. Replacing LAMSs with DPSs in DPDS patients was associated with a lower recurrence rate., (© 2024. The Author(s).)

Objectives: Advancements in technology have improved healthcare quality but shifted the focus to efficiency, negatively impacting patient- doctor relationships. This study proposes integrating social-emotional learning (SEL) into medical education to address this issue., Key Arguments: Social-emotional learning (SEL) is based on social learning theory and has a focus on emotion management, stress management, empathy, and social skills. Through SEL, students can develop social and emotional skills by observing, interacting with, and imitating others. Incorporating SEL into medical education would ensure that physicians develop the social and emotional skills necessary to form positive relationships with patients and to cope with the emotional demands of medical work. SEL comprises six domains, namely, the cognitive, emotion, social, values, perspective, and identity domains. These six domains are closely related to the six core competencies the Accreditation Council for Graduate Medical Education (ACGME) indicated every doctor should possess, which indicates that the domains of SEL are highly relevant within the context of medical education. Furthermore, SEL can lead to the development of empathy, which can improve physicians' ability to understand patients' perspectives and emotions, and resilience, which can enable physicians to more effectively cope with the demands of their work, and it can lead to holistic development, with doctors gaining an understanding of both the technical and humanistic aspects of their work., Conclusion: Incorporating SEL in medical education would enable doctors to develop key social and emotional skills that would improve their ability to provide holistic medical services and therefore would improve overall medical systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hsu, Fuh and Liao.)

Background: The objective was to elucidate the effect of tibolone vs hormone replacement therapy (HRT) on climacteric symptoms and psychological distress., Methods: All consecutive women with climacteric symptoms were allocated to receive tibolone (2.5 mg) or estradiol valerate (1 mg) plus medroxyprogesterone acetate (2.5 mg)., Results: The improvement in "feeling dizzy or faint" after tibolone treatment was more prominent than that after HRT (-0.7 ± 0.8 vs -0.0 ± 0.9, p = 0.004). In addition, other climacteric symptoms, including anxiety, depression, somatic symptoms, and vasomotor symptoms, and sexual function improved after tibolone and HRT, but there were no between-group differences. Psychological distress assessment demonstrated that somatic complaints, obsessive-compulsive symptoms, depressive symptoms, hostility, additional symptoms, and the General Symptom Index improved after tibolone treatment and HRT, but there were no between-group differences. Personality traits assessment revealed that neuroticism improved after tibolone treatment., Conclusion: Tibolone seems more beneficial than HRT in treating symptoms of dizziness and faintness. Both tibolone and HRT could improve psychological distress., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

With an estimated prevalence of 1 in 1000 individuals globally, autosomal dominant polycystic kidney disease (ADPKD) stands as the most prevalent inherited renal disorder. Ultrasonography (US) is the most widely used imaging modality in the diagnosis and monitoring of ADPKD. This review discusses the role of US in the evaluation of ADPKD, including its diagnostic accuracy, limitations, and recent advances. An overview of the pathophysiology and clinical manifestations of ADPKD has also been provided. Furthermore, the potential of US as a noninvasive tool for the assessment of disease progression and treatment response is examined. Overall, US remains an essential tool for the management of ADPKD, and ongoing research efforts are aimed at improving its diagnostic and prognostic capabilities., Competing Interests: Prof. Chien-Te Lee, an editorial board member at Journal of Medical Ultrasound, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2024 Journal of Medical Ultrasound.)

Aim: No previous studies, to our knowledge, have investigated the association between psychiatrist density and suicide, accounting for individual- and area-level characteristics., Methods: We investigated all suicide cases in 2007-2017 identified from the national cause-of-death data files, with each suicide case matched to 10 controls by age and sex and each suicide case/control assigned to one of the 355 townships across Taiwan. Our primary outcome was the odds ratio (OR) of suicide and its 95% confidence interval (CI) estimated via multilevel models, which included both individual- and area-level characteristics. Townships with no psychiatrists were compared with the quartiles of townships with psychiatrists (density per 100,000 population): quartile 1 (Q1) (0.01-3.02); quartile 2 (Q2) (3.02-7.20); quartile 3 (Q3) (7.20-13.82); and quartile 4 (Q4) (>13.82)., Results: A total of 40,930 suicide cases and 409,300 age- and sex-matched controls were included. We found that increased psychiatrist density was associated with decreased suicide risk (Q1: adjusted OR [aOR], 0.95 [95% CI, 0.90-1.01]; Q2: aOR, 0.90 [95% CI, 0.85-0.96]; Q3: aOR, 0.89 [95% CI, 0.83-0.94]; Q4: aOR, 0.89 [95% CI, 0.83-0.95]) after adjusting for individual-level characteristics (employment state, monthly income, physical comorbidities, and the diagnosis of psychiatric disorders) and area socioeconomic characteristics., Conclusions: The psychiatrist density-suicide association suggests an effect of increased availability of psychiatric services on preventing suicide. Suicide prevention strategies could usefully focus on enhancing local access to psychiatric services., (© 2023 The Authors. Psychiatry and Clinical Neurosciences © 2023 Japanese Society of Psychiatry and Neurology.)

Hepatic events can occur after discontinuing antiviral therapy. We investigated factors associated with hepatitis flares and hepatic decompensation after discontinuing tenofovir disoproxil fumarate (TDF) and entecavir (ETV). Hepatitis flares within 6 months and hepatic decompensation were compared between non-cirrhotic hepatitis B e antigen-negative patients after discontinuing TDF or ETV by using the Cox proportional hazard model. The cumulative rates of hepatitis flare at 6 months after discontinuing ETV and TDF were 2% and 19%, respectively ( p < 0.001). The respective rates of hepatic decompensation at 6 months were 0% and 7% ( p = 0.009). Higher alanine aminotransferase (ALT) (AASLD criteria) at the end of treatment (EOT) (HR = 4.93; p = 0.001), an off-therapy dynamic change in HBV DNA (rapid rebound of HBV DNA from the nadir, ≥1 log 10 IU/mL per month) (HR = 10.7; p < 0.001), and the discontinuation of TDF (HR = 6.44; p = 0.006) were independently associated with hepatitis flares within 6 months. Older age (HR = 1.06; p < 0.001) and an off-therapy dynamic change in HBV DNA (HR = 3.26; p = 0.028) were independently associated with hepatic decompensation after the discontinuation of antiviral therapy. In summary, we demonstrated several factors associated with hepatitis flares and hepatic decompensation after discontinuing antiviral therapy in non-cirrhotic hepatitis B e antigen-negative patients.

Background: Adult preventive health checkups with depression screening were launched in August 2011 in Taiwan; however, its impact has not yet been evaluated. This study aimed to use real-world data to assess the effectiveness of depression screening among middle-aged and older adults., Methods: A total of 4,972,228 adults aged 40 years and above who participated in a health checkup with depression screening between 2013 and 2019 and the same number of unscreened counterparts were included. The target trial emulation study was conducted to estimate the hazard ratios (HRs) for newly treated depression, psychiatric hospitalisation, and suicide. The changes in HRs during the study period were assessed using interval Cox models., Findings: The screening group had a higher rate of newly treated depression (HR 1.63 [95% CI 1.62, 1.64]) and a lower risk of psychiatric hospitalisation (HR 0.93 [95% CI 0.91, 0.95]). There was a null association between depression screening and suicide; however, a higher suicide risk was found in screened older adults aged 65 years and above. Only 10.8% received depression treatment during the study period among the screen-positive individuals., Interpretation: Health checkups with depression screening could potentially promote depression treatment and reduce the risk of psychiatric hospitalisation; however, there was no effect on suicide. The treatment rate for depression remained low after screening for depression. Further attention to enhance referral and treatment is required., Funding: The study was funded by the National Health Research Institutes, Taiwan., Competing Interests: During preparing this work, the authors used ChatGPT-3.5 and Grammarly to enhance writing quality and rectify grammar errors. Subsequently, the authors reviewed and edited the content, assuming full responsibility for the publication's integrity. The authors declared no relevant conflict of interest., (© 2023 The Author(s).)

Background: Patients with common mental disorders (depression, anxiety, and somatic symptoms) often exhibit lower heart rate variability (HRV) than healthy individuals. Under the hypothesis that disorder status affects cognitive function, we examined whether neuropsychological features can be mediators between psychopathologies and HRV and possible sex differences., Methods: We recruited 359 individuals (aged 42.47 ± 12.23) with and without common mental disorders. Questionnaires were used to measure their psychopathologies. Eight tests from the Cambridge Neuropsychological Test Automated Battery were selected to measure neuropsychological functions. Resting-state HRV measurements were obtained for 5 min. The associations among these constructs were analyzed using multiple linear regression analysis and structural equation modelling., Results: Among women, Reaction Time (RTI, a task of psychomotor speed) indicator mediated the relationship between depression and low-frequency power (LF); Emotion Recognition Task (ERT, a task of emotional regulation) indicator mediated the relationship between health anxiety and high-frequency power (HF). Among men, Intra-Extra Dimensional Set Shift (IED, a task of shifting) indicator mediated the relationship between depression and LF; Match to Sample Visual Search (MTS, a task of selective attention) indicator mediated the relationship between health cognition and HF. The depression-RTI-LF pathway in women tended to lower HRV; whereas health anxiety-ERT-HF in women, depression-IED-LF and health cognition-MTS-HF in men tended to increase HRV., Limitations: Possible medication effects; not directly measuring brain activity; only gathering resting-state HRV., Conclusion: Our findings support the notion that neuropsychological features mediate the relationship between psychopathologies and HRV, and that sex differences exist., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Youth suicide rates have increased markedly in some countries. This study aimed to estimate the population-attributable risk of psychiatric disorders associated with suicide among Taiwanese youth aged 10-24 years., Methods: Data were obtained from the National Death Registry and National Health Insurance (NHI) claims database between 2007 and 2019. Youth who died by suicide were included, and comparisons, 1:10 matched by age and sex, were randomly selected from the Registry for NHI beneficiaries. We used multivariable logistic regression to estimate suicide odds ratios for psychiatric disorders. The population-attributable fractions (PAF) were calculated for each psychiatric disorder., Results: A total of 2345 youth suicide and 23 450 comparisons were included. Overall, 44.8% of suicides had a psychiatric disorder, while only 7.9% of the comparisons had a psychiatric disorder. The combined PAF for all psychiatric disorders was 55.9%. The top three psychiatric conditions of the largest PAFs were major depressive disorder, dysthymia, and sleep disorder. In the analysis stratified by sex, the combined PAF was 45.5% for males and 69.2% for females. The PAF among young adults aged 20-24 years (57.0%) was higher than among adolescents aged 10-19 years (48.0%)., Conclusions: Our findings of high PAF from major depressive disorder, dysthymia, and sleep disorder to youth suicides suggest that youth suicide prevention that focuses on detecting and treating mental illness may usefully target these disorders.

Venous thromboembolism (VTE) is common in patients with trauma, and thromboprophylaxis has been advocated. However, conflicting results regarding VTE rates in the Asian population following orthopaedic procedures have been presented. We aimed to investigate the VTE incidence in Taiwanese patients with pelvic and/or acetabular fractures and identify the associated risk factors. We included 402 patients who underwent surgery for pelvic and/or acetabular fractures. All patients received mechanical thromboprophylaxis with graduated compression stockings. Duplex scanning was performed postoperatively or during follow-up when signs or symptoms of deep vein thrombosis (DVT) developed. Variables with a significance level of ≤ 0.1 in the univariate analyses were introduced into the multivariate logistic regression analysis to identify DVT risk factors. The overall DVT and symptomatic pulmonary embolism (PE) rate was 3.48% (14/402 patients). Among patients with DVT, 46.1% were asymptomatic. Patients with VTE were significantly older than those without. Multivariate logistic regression analysis revealed that age was a VTE risk factor. The incidence of DVT and symptomatic PE in our cohort was low. Advanced age was a risk factor for VTE. These findings could help clinicians develop appropriate prevention and treatment strategies for VTE in Taiwanese patients with pelvic and/or acetabular fractures., (© 2023. The Author(s).)

Background: Due to COVID-19, face-to-face service activities in service-learning courses have become unfeasible. To address this challenge, this study aims to integrate project-based learning into medical education's service-learning curriculum. This study also seeks to evaluate the effectiveness of this instructional approach and identify factors that influence its success., Methods: A total of 135 first-year medical students enrolled in a mandatory 1-credit service-learning course were recruited. The course involved various service activities aligned with the needs of the local community. The students were organized into 12 groups, each working on different service-learning projects, such as raising health awareness or educating the public about specific diseases. Following the completion of the course, a questionnaire was distributed among the students to gather feedback on the course, and 122 (valid responses were collected, representing a response rate of 90.3%)., Results: The results indicated that the project-based service-learning course significantly improved students' "interpersonal communication skills," their ability to "learn and grow from work," and their sense of "professionalism" (all p ≤ 0.037). Among the various aspects of service learning, the highest agreement was observed for "executing the project," followed by "group discussions and project formulation," "overall course review," "review of project outcomes," "outcome presentations," "teaching proposal writing and project brainstorming," "sharing of service-learning experiences by teachers," and "sharing of service-learning experiences by teaching assistants." Students also found certain factors to be beneficial in enhancing the learning effectiveness of service-learning courses, including "prize money for service-learning outcomes," "funding for service-learning activities," and "consultations from medical personnel" (all p ≤ 0.01). However, "course credit" and "photography software" did not show significant effects (both p > 0.05). The most preferred resources or activities for future service-learning courses were "course credit" and "face-to-face service-learning activities.", Conclusions: The project-based learning method improved the learning effectiveness in service-learning courses. Students perceived that the number of course credits reflects the course value and plays a pivotal role in enhancing the learning effectiveness in service-learning courses. During the epidemic, students still expect to have face-to-face service activities in service-learning courses. Therefore, without the impact of the epidemic, service learning courses should return to face-to-face service activities., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Real-world data sources can facilitate essential understanding of the epidemiological features of anaphylaxis. However, the accuracy of case-identifying definitions based on diagnosis codes for anaphylaxis in healthcare databases remains understudied. We conducted a cross-sectional study analyzing claims data from the largest multi-institutional healthcare system in Taiwan during 2017-2021. We included patients with incident anaphylaxis identified by either ICD-10-CM codes for anaphylaxis (Group 1) or ICD-10-CM codes for severe allergic or drug adverse events and additional modifier codes for acute allergy events (Group 2). We randomly selected 20% of the cases to determine the positive predictive value (PPV) of anaphylaxis case-identifying definitions in Groups 1 and 2 after review of electronic medical records by two physicians. From the original cohort (n = 2,176), we randomly selected 433 patients with either a diagnosis of anaphylaxis (Group 1), or a diagnosis of severe allergic and drug adverse events with additional modifier codes for acute allergy events (Group 2). In Group 1, we judged 135 / 170 patients as true anaphylaxis cases, giving a PPV of 79.4% (95% CI: 73.3-85.5). In Group 2, we judged 47 / 263 patients as true anaphylaxis cases, giving a PPV of 17.9% (95% CI: 13.3-22.5). In conclusion, acceptable PPVs were observed when anaphylaxis cases were identified by ICD-10-CM codes for anaphylaxis, but not by ICD-10-CM codes for severe allergic or drug adverse event with additional modifier codes for acute allergy events. Our multi-institutional findings could serve as a fundamental reference for further studies of anaphylaxis based on real-world healthcare databases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Molnupiravir is an essential oral antiviral agent against coronavirus disease 2019 (COVID-19); however, its real-world effectiveness has not been evaluated in patients undergoing haemodialysis (HD)., Methods: This multi-centre retrospective study, involving 225 patients undergoing HD with initially mild or asymptomatic COVID-19, was conducted to compare the risks of 30-day COVID-19-related acute care visits between patients receiving and not receiving molnupiravir. Patients who received molnupiravir were stratified by rapid antigen detection (RAD) test results on day 7 after disease onset to assess whether rapid molnupiravir introduction accelerated viral clearance., Results: Thirty-day COVID-19-related acute care visits were reported in 9.41% and 21.74% of the molnupiravir and control groups, respectively, and use of molnupiravir markedly reduced the risk of acute care visits after adjusting for baseline characteristics via propensity score weighting [hazard ratio 0.218, 95% confidence interval (CI) 0.074-0.642; P=0.006]. The tolerability of molnupiravir in the enrolled patients was generally acceptable, with only 11.88% of molnupiravir users reporting mild adverse events. Moreover, rapid initiation of molnupiravir within 1 day of COVID-19 onset was an independent predictor of conversion to a negative RAD test result on day 7 after disease onset (odds ratio 6.207, 95% CI 2.509-15.358; P<0.001)., Conclusions: Molnupiravir is well tolerated and decreases the medical needs in patients with COVID-19 undergoing HD. Furthermore, the rapid initiation of molnupiravir accelerates viral clearance in patients with COVID-19 undergoing HD. These findings highlight the therapeutic role of molnupiravir for this vulnerable population., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lung cancer is the most common malignant cancer worldwide. Combination therapies are urgently needed to increase patient survival. Calycosin is a phytoestrogen isoflavone that has been reported previously to inhibit tumor cell growth, although its effects on lung cancer remain unclear. The aim of this study was to investigate the effects of calycosin on cell proliferation and apoptosis of gemcitabine-resistant lung cancer cells. Using calycosin to treat human lung cancer cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0 GEMR) and examine the effects on the cells. Cultured human lung cancer cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0 GEMR) were treated with increasing concentrations of calycosin. Cell viability and apoptosis were studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide, flow cytometry, and TUNEL assays. Western blots were used to measure the expression levels of proliferation-related proteins and cancer stem cell proteins in CL1-0 GEMR cells. The results showed that calycosin treatment inhibited cell proliferation, decreased cell migration ability, and suppressed cancer stem cell properties in CL1-0 GEMR cells. Interestingly, in CL1-0 GEMR cells, calycosin treatment not only increased LDOC1 but also decreased GNL3L/NFκB protein levels and mRNA levels, in concentration-dependent manners. We speculate that calycosin inhibited cell proliferation of the gemcitabine-resistant cell line through regulating the LDOC1/GNL3L/NFκB pathway., Competing Interests: None

Aims: We explored long-term employment status and income before and after depression diagnosis among men and women and at different working ages in Taiwan., Methods: Data from 2006 to 2019 were obtained from the National Health Insurance Research Database (NHIRD). Individuals with newly diagnosed depressive disorder aged 15 to 64 years during the study period were identified. An equal number of individuals without depression were matched for their demographic and clinical characteristics. Employment outcomes included employment status, which was categorized into employed or unemployed, and annual income. Based on the occupation categories and monthly insurance salary recorded in the Registry for Beneficiaries of the NHIRD, a subject was defined as unemployed if he or she differed from the income earner or the occupation category was unemployed. Monthly income was defined as zero for unemployed subjects and proxied as monthly insurance salary for others. Annual income was the sum of monthly income in each observation year., Results: A total of 420,935 individuals with depressive disorder were included in the study, and an equal number of individuals with not diagnosed depression served as controls. Employment rate and income were lower in the depression group than in the control group before the year of diagnosis, with a difference of 5.7% in employment rate and USD 1,173 in annual income. This gap increased considerably after the year of diagnosis (7.3% in employment rate and USD 1,573 in annual incomes) and further widened in the subsequent years (8.1% in employment rate and USD 2,006 in annual incomes in the 5th following year). The drops in the employment rate and income caused by depression were more evident in men and older age groups than in women and younger age groups, respectively. However, the reduction in employment rate and income in the following years after the diagnosis was more considerable among younger age groups., Conclusions: The effect of depression on employment status and income was significant during the year of diagnosis and continued afterwards. The effect on employment outcomes varied between genders and across all age groups.

Objectives: We used machine learning to incorporate three types of biomarkers (respiratory sinus arrhythmia, RSA; skin conductance, SC; finger temperature, FT) for examining the performance of diagnosing somatic symptom disorder (SSD)., Methods: We recruited 97 SSD subjects and 96 controls without psychiatric history or somatic distress. The values of RSA, SC and FT were recorded in three situations (resting state, under a cognitive task and under paced breathing) and compared for the two populations. We used machine learning to combine the biological signals and then applied receiver operating characteristic curve analysis to examine the performance of diagnosing SSD regarding the distinct indicators and situations. Subgroup analysis for subjects without depression/anxiety was also conducted., Results: FT was significantly different between SSD patients and controls, especially in the resting state and under paced breathing. However, the biomarkers (0.75-0.76) did not reveal an area under the curve (AUC) comparable with the psychological questionnaires (0.86). Combining the biological and psychological indicators gave a high AUC (0.86-0.92). When excluding individuals with depression/anxiety, combining three biomarkers (0.79-0.83) and adopting psychological questionnaires (0.78) revealed a similar AUC., Conclusions: The performance of RSA/SC/FT was unsatisfactory for diagnosing SSD but became comparable when excluding comorbid depression/anxiety.

As a super-resolution imaging method, stimulated emission depletion (STED) microscopy has unraveled fine intracellular structures and provided insights into nanoscale organizations in cells. Although image resolution can be further enhanced by continuously increasing the STED-beam power, the resulting photodamage and phototoxicity are major issues for real-world applications of STED microscopy. Here we demonstrate that, with 50% less STED-beam power, the STED image resolution can be improved up to 1.45-fold using the separation of photons by a lifetime tuning (SPLIT) scheme combined with a deep learning-based phasor analysis algorithm termed flimGANE (fluorescence lifetime imaging based on a generative adversarial network). This work offers a new approach for STED imaging in situations where only a limited photon budget is available.

Background and Objectives: The effectiveness and safety of idarucizumab for the reversal of the effects of dabigatran have been proven. However, there remains a paucity of literature comprehensively investigating outcomes in real-world patients. This is especially true when comparing patients who were eligible for inclusion in the RE-VERSE AD trial with patients who were ineligible. As the prescription of dabigatran has become increasingly popular, the generalizability of the results to real-world populations has come into question due to the broad variability of real-world patients receiving dabigatran. Our study aimed to identify all patients who were prescribed idarucizumab and examined how effectiveness and safety varied among those patients who were eligible and ineligible for the trial. Materials and Methods : This retrospective cohort study analyzed the largest medical database in Taiwan. We enrolled all patients who were prescribed and received idarucizumab from when it became available in Taiwan up until May 2021. A Total of 32 patients were included and analyzed, and they were further divided into subgroups based on their eligibility for inclusion in the RE-VERSE AD trial. Multiple outcomes were evaluated, including successful hemostasis rate, complete reversal efficacy of idarucizumab, 90-day thromboembolic events, intra-hospital mortality, and adverse event rate. Results : In our study, we found that 34.4% of real-world cases of idarucizumab use were ineligible for the RE-VERSE AD trials. The eligible group had higher successful hemostasis rates (95.2% vs. 80%) and anticoagulant effect reversal rates compared to the ineligible group (73.3% vs. 0%). The mortality rates were 9.5%, compared to 27.3% in the ineligible group. Few adverse effects (n = 3) and 90-day thromboembolic events (n = 1) were observed in either group. Among the ineligible cases, all acute ischemic stroke patients (n = 5) received definite, timely treatments without complications. Conclusions: Our study demonstrated the real-world effectiveness and safety of idarucizumab infusion for trial-eligible patients and all acute ischemic stroke patients. However, although it seems to be effective and safe, idarucizumab appears to be less effective in other trial-ineligible patients. Despite this result, our study provides further evidence for extending the applicability of idarucizumab in real-world scenarios. Our study suggests that idarucizumab can be a safe and effective option for reversing the anticoagulant effect of dabigatran, particularly for eligible patients.

Objective: The objective of this study was to compare two tools, the Intensive Care Delirium Screening Checklist (ICDSC) and Confusion Assessment Method for the intensive care unit (ICU) (CAM-ICU), for their predictive validity for outcomes related to delirium, hospital mortality, and length of stay (LOS)., Methods: The prospective study conducted in six medical ICUs at a tertiary care hospital in Taiwan enrolled consecutive patients (≥20 years) without delirium at ICU admission. Delirium was screened daily using the ICDSC and CAM-ICU in random order. Arousal was assessed by the Richmond Agitation-Sedation Scale (RASS). Participants with any one positive result were classified as ICDSC- or CAM-ICU-delirium groups., Results: Delirium incidence evaluated by the ICDSC and CAM-ICU were 69.1% (67/97) and 50.5% (49/97), respectively. Although the ICDSC identified 18 more cases as delirious, substantial concordance (κ = 0.63; p < 0.001) was found between tools. Independent of age, Acute Physiology and Chronic Health Evaluation II score, and Charlson Comorbidity Index, both ICDSC- and CAM-ICU-rated delirium significantly predicted hospital mortality (adjusted odds ratio: 4.93; 95% confidence interval [CI]:1.56 to 15.63 vs. 2.79; 95% CI: 1.12 to 6.97, respectively), and only the ICDSC significantly predicted hospital LOS with a mean of 17.59 additional days compared with the no-delirium group. Irrespective of delirium status, a sensitivity analysis of normal-to-increased arousal (RASS≥0) test results did not alter the predictive ability of ICDSC- or CAM-ICU-delirium for hospital mortality (adjusted odds ratio: 2.97; 95% CI: 1.06 to 8.37 vs. 3.82; 95% CI: 1.35 to 10.82, respectively). With reduced arousal (RASS<0), neither tool significantly predicted mortality or LOS., Conclusions: The ICDSC identified more delirium cases and may have higher predictive validity for mortality and LOS than the CAM-ICU. However, arousal substantially affected performance. Future studies may want to consider patients' arousal when deciding which tool to use to maximise the effects of delirium identification on patient mortality., (Copyright © 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the preoperative influential factors of difficult thyroidectomy and establish a preoperative nomogram for predicting the difficulty of thyroidectomy., Methods: A total of 753 patients who underwent total thyroidectomy with central lymph node dissection between January 2018 and December 2021 were retrospectively enrolled in this study and randomly divided into training and validation groups at a ratio of 8:2. In both subgroups, the patients were divided into difficult thyroidectomy and nondifficult thyroidectomy groups based on the operation time. Patient age, sex, body mass index (BMI), thyroid ultrasound, thyroid function, preoperative fine needle aspiration (FNA), postoperative complications and other data were collected. Logistic regression analysis was performed to identify the predictors of difficult thyroidectomy, and a nomogram predicting surgical difficulty was created., Results: Multivariate logistic regression analysis demonstrated that male sex (OR = 2.138, 95% CI 1.055-4.336, p = 0.035), age (OR = 0.954, 95% CI 0.932-0.976, p < 0.001), BMI (OR = 1.233, 95% CI 1.106-1.375, p < 0.001), thyroid volume (OR = 1.177, 95% CI 1.104-1.254, p < 0.001) and TPO-Ab (OR = 1.001, 95% CI 1.001-1.002, p = 0.001) were independent risk factors for difficult thyroidectomy. The nomogram model incorporating the above predictors performed well in both the training and validation sets. A higher postoperative complication rate was found in the difficult thyroidectomy group than in the nondifficult thyroidectomy group., Conclusion: This study identified independent risk factors for difficult thyroidectomy and created a predictive nomogram for difficult thyroidectomy. This nomogram may help to objectively and individually predict surgical difficulty before surgery and provide optimal treatment., (© 2023. The Author(s).)

Background: Subjective sleep quality may reflect the mental well-being of migrant care workers; however, the related occupational factors remain unclear. This study examines the association between the characteristics of care labor and the subjective sleep quality of female migrants., Methods: In this cross-sectional study, Southeast Asian migrant care workers in Taiwan were recruited using convenience sampling. Data on working conditions, including workplace setting, wage, working hours, psychiatric symptoms of care recipients, and sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI), were collected through computer-assisted personal interviews. Multiple linear regression analyses were performed to determine the independent relationship between working conditions and the PSQI global score., Results: There were 220 institution-(47.7%) and home-based (52.3%) care workers, and 47.7% had a PSQI score higher than 5. After controlling for covariates, the lowest tertile of wages and daily working hours (> 8 h) were independently correlated with poor sleep quality. Moreover, in the stepwise regression model, wage and working hours remained the most explainable correlates of poor sleep quality., Conclusion: This study lent support to the notion that low wages and long working hours are significant occupational factors that negatively impact the subjective sleep quality of female Southeast Asian migrant care workers in Taiwan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Lin, Chien, Chen, Chan, Liao, Kuo and Chen.)

Previous meta-analyses have produced conflicting conclusions about suicidality risk among psoriasis patients. We aimed to update the evidence on the risk for the whole continuum of incident suicidality in psoriasis patients. We performed an update systematic review and meta-analysis and searched CENTRAL, PubMed, and Embase from January 1, 2017 to August 14, 2021 for relevant new cohort studies and incorporated new studies into our previous systematic review. Random-effects model meta-analysis was used to obtain pooled hazard ratio (HR) with 95% confidence interval (CI). Subgroup analysis was conducted according to age and disease severity. A total of 12 studies were included in this meta-analysis. We detected no significant differences in the risk for incident completed suicide (HR 1.33, 95% CI 0.91-1.95), suicide attempt (HR 1.22, 95% CI 0.96-1.56), suicidal behavior (HR 1.08, 95% CI 0.98-1.19), and suicide ideation (HR 1.74, 95% CI 0.99-3.06) between psoriasis patients and non-psoriatic controls. In the subgroup analysis based on age, an increased risk for incident suicide ideation was observed in pediatric subgroup (HR 1.50, 95% CI 1.12-2.03). The updated evidence suggests no increased risk for whole continuum of incident suicidality spectrum in psoriasis patients but an increased risk for incident suicide ideation among pediatric psoriasis patients. Involving mental health professionals may be crucial in psoriasis management especially in young patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We investigated recent trends in youth suicide and their associations with societal and psychological factors in Taiwan., Methods: Suicide data (1971-2019) for 10-24 year olds were extracted from Taiwan's national cause-of-death data files. We investigated changes in trends in youth suicide rates, societal factors (gross domestic product per capita, Gini index, overall and youth unemployment rates, divorce rates in people aged 40-59 years [i.e. the age of most 15-24 year olds' parents] and Internet use rates) and psychological distress indicators (youth self-harm rates and the prevalence of worry-related insomnia, and suicide ideation, plan and attempt) using joinpoint regression and graphic examinations. The associations of these factors with youth suicide rates were examined using Prais-Winsten regression., Results: Suicide rates in Taiwan's 10-24 year olds changed from a downward trend (2005-2014) to an upward trend in 2014 and increased 11.5% (95% confidence interval = [5.2%, 18.1%]) annually between 2014 and 2019. There was also an upturn in divorce rates among females aged 40-59 years in 2014 and self-harm rates among 15- to 24-year-old youth in 2013. The prevalence of self-reported insomnia and suicide ideation, plan and attempt in youth started to increase from 2013 to 2016. In the regression analysis, Internet use, female divorce rates and youth self-harm rates were positively associated with youth suicide rates., Conclusion: Suicide rates and the prevalence of suicidal behaviors began to increase in Taiwanese youth in the 2010s. These increases may be associated with concurrent rises in parental divorce rates, Internet use and poor sleep. Further research is needed to examine the mechanisms underlying recent increases in youth suicide risk.

Universal antenatal education has been offered to expectant mothers in Taiwan since 2014. Depression screening is included in the offered education sessions. This study aimed to examine the association of antennal education and depression screening with mental health outcomes, including perinatal depression diagnosis and psychiatrist visits. Data was obtained from the antenatal education records and Taiwan's National Health Insurance claims database. A total of 789,763 eligible pregnant women were included in the current study. The psychiatric-related outcomes were measured between antenatal education and the six-month after delivery. It was found that the antenatal education was widely used in Taiwan, and the attendance rate has increased to 82.6% since its launch. The attenders were more likely to be from disadvantaged backgrounds, and 5.3% of them were screened positive for depressive symptoms. They were also more likely to visit a psychiatrist but less likely to be diagnosed with depression than the non-attenders. Factors including young age, high healthcare utilization, and comorbid psychiatric disorder history were consistently associated with depression symptoms, perinatal depression diagnoses and psychiatrist visits. Further research is needed to understand the reasons for the nonattendance at antenatal education programmes and the barriers to utilizing mental health services., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Identifying the relevant factors for suicidality in individuals with conduct problems is a public health concern, especially if they were under the influence of mood disorders later in life. This study investigates the relationship between youth conduct problems and mood disorders and adulthood suicidality, and to further explore the mediating effects of personality on this relationship. A retrospective cohort study was administered to 308 individuals aged 20-65 years, with or without mood disorders diagnosed by psychiatrists. The Composite International Diagnosis Interview was used to evaluate conduct problems in youth and suicidality (i.e., suicide plan and suicide attempt) in the past year. Personality traits were assessed using Eysenck Personality Questionnaire-Revised for extraversion and neuroticism. Multiple-mediator analysis was used to investigate the mediation effects of personality traits on the relationship between conduct problems and suicidality. The average age of enrolled participants was 31.6 years, and 42.5% of them were female. 39.2% reported suicidality and 43.2% reported conduct problems in youth. Participants who were diagnosed with mood disorders (p < 0.001) and reported having conduct problems (p = 0.004) were associated with high suicidality. Multiple-mediator analysis showed that conduct problems in youth increased the risk of adulthood suicidality through the indirect effects of higher neuroticism (suicide plan: OR = 1.30, BCA 95% CI = 1.04-1.83; suicide attempt: OR = 1.27, BCA 95% CI = 1.05-1.66). Neuroticism mediates the association between youth conduct problems and adulthood suicidality. This finding raises our attention to assess personality traits in individuals with youth conduct problems for designing proper intervention strategies to reduce the risk of suicide., (© 2023. The Author(s).)

Diabetes-induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin-like growth factor II receptor α (IGF-IIRα) is a cardiac risk factor. In this study, we hypothesized IGF-IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague-Dawley rat model with specific IGF-IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF-IIRα in diabetic hearts. The results showed that IGF-IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro-inflammatory factors, such as Tumor necrosis factor-alpha, Interleukin-6, Cyclooxygenase-2, Inducible nitric oxide synthase, and Nuclear factor-kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac-specific IGF-IIRα overexpression. Correspondingly, IGF-IIRα overexpression in the diabetic myocardium also reduced the PI3K-AKT survival axis and activated mitochondrial-dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac-specific IGF-IIRα overexpression. Overall, all results provid clear evidence that IGF-IIRα can enhance cardiac damage and is a harmful factor to the heart under high-blood glucose conditions. However, the pathophysiology of IGF-IIRα under different stresses and its downstream regulation in the heart still require further research., (© 2022 Wiley Periodicals LLC.)

Parkinson's disease (PD), a chronic and progressive neurodegenerative disease, can reduce the population of dopaminergic neurons in the substantia nigra. The cause of this neuronal death remains unclear. 1-Methyl-4-phenylpyridinium ion (MPP+) is a potent neurotoxin that can destroy dopaminergic (DA) neurons and promote PD. Garcinol, a polyisoprenylated benzophenone derivative, was extracted from Garcinia indica and is an important active compound it has been used as an anticancer, antioxidant, and anti-inflammatory, agent and it can suppress reactive oxygen species (ROS) mediated cell death in a PD model. Human neuroblastoma (SH-SY5Y) cells (1 × 10 5  cells) were treated with MPP+ (1 mM) for 24 h to induce cellular ROS production. The formation of ROS was suppressed by pretreatment with different concentrations of garcinol (0.5 and 1.0 μM) for 3 h in SH-SY5Y cells. The present study found that MPP+ treatment increased the formation of reactive oxygen species (ROS), and the increased ROS began to promote cell death in SH-SY5Y cells. However, our natural compound garcinol effectively blocked MPP+-mediated ROS formation by activating the DJ-1/SIRT1 and PGC-1α mediated antioxidant pathway. Further findings indicate that the activated SIRT1 can also regulate p-AMPK-mediated autophagy to protect the neurons from the damage it concludes that garcinol sub-sequential regulates intracellular autophagy in this model, and the productive efficacy of garcinol was confirmed by western blot analysis and MitoSOX DCFDA and MTT assays. The results showed garcinol increased protection due to the prevention of MPP+-induced ROS and the promotion of cell survival., (© 2023 Wiley Periodicals LLC.)

Parkinson's disease (PD) is a common disorder attributed to the loss of midbrain dopamine (mDA) neurons and reduced dopamine secretion. Currently, the treatment regimes for PD comprise deep brain stimulations, however, it attenuates the PD progression marginally and does not improve neuronal cell death. We investigated the function of Ginkgolide A (GA) to reinforce Wharton's Jelly-derived mesenchymal stem cells (WJMSCs) for treating the in vitro model of PD. GA enhanced the self-renewal, proliferation, and cell homing function of WJMSCs as assessed by MTT and transwell co-culture assay with a neuroblastoma cell line. GA pre-treated WJMSCs can restore 6-hydroxydopamine (6-OHDA)-induced cell death in a co-culture assay. Furthermore, exosomes isolated from GA pre-treated WJMSCs significantly rescued 6-OHDA-induced cell death as determined by MTT assay, flow cytometry, and TUNEL assay. Western blotting showed that apoptosis-related proteins were decreased following GA-WJMSCs exosomal treatment which further improved mitochondrial dysfunction. We further demonstrated that exosomes isolated from GA-WJMSCs could restore autophagy using immunofluorescence staining and immunoblotting assay. Finally, we used the alpha-synuclein recombinant protein and found that exosomes derived from GA-WJMSCs led to the reduced aggregation of alpha-synuclein compared to that in control. Our results suggested that GA could be a potential candidate for strengthening stem cell and exosome therapy for PD.