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Yueh-Chang Lee,1 Nancy Chen,1 I-Tsong Huang,2–4 Hui-Hua Yang,2 Chin-Te Huang,1 Li-Kuang Chen,2–5 Min-Muh Sheu1,6,7 1Department of Ophthalmology, 2Taiwan CDC Collaborating Laboratories of Virology, 3Department of Laboratory Medicine, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan; 4Graduate Institute of Medical Sciences, 5Department of Laboratory Diagnosis, 6Department of Ophthalmology and Visual Science, Tzu-Chi University, Hualien, Taiwan; 7Department of Ophthalmology, Mennonite Christian Hospital, Hualien, Taiwan Abstract: Epidemic viral conjunctivitis is a highly contagious disease that is encountered year-round. The causative agents are mainly adenoviruses and enteroviruses. It occurs most commonly upon infection with subgroup D adenoviruses of types 8, 19, or 37. For common corneal involvement of human adenovirus type 8 epidemic keratoconjunctivitis, full-layer epithelial detachment is rarely seen. Herein, we report three cases of epidemic keratoconjunctivitis during an outbreak which manifested as large corneal epithelial full-layer detachment within a few days. The lesions healed without severe sequelae under proper treatment. The unique manifestation of this outbreak may indicate the evolution of human adenovirus type 8. Keywords: EKC, HAdV-8, cornea, virology, epidemic viral conjunctivitis

Background: A fracture of the greater trochanter through an osteolytic lesion may occur as a late complication after total hip arthroplasty. The optimal treatment for this difficult complication remains controversial. We have treated this problem with internal fixation and allogeneic bone-grafting at the time of revision of a loose acetabular component.Methods: We retrospectively reviewed the results of treatment of a fracture through an osteolytic lesion of the greater trochanter in nineteen patients seen from 1996 to 2002. All fractures were treated with morselized allogeneic bone grafts and wire fixation at the time of revision of a failed acetabular component. Postoperative care included the use of an abduction orthosis and protected weight-bearing for at least three months. Follow-up of all patients consisted of radiographic examinations and clinical evaluation with use of the Harris hip score.Results: At an average duration of 3.8 years after the revision, eighteen of the nineteen fractures had healed. The average time to healing was five months. The one treatment failure occurred in a patient who did not comply with the use of an abduction orthosis. The average Harris hip score for all patients improved from 32.5 points preoperatively to 91.2 points at the time of the latest follow-up. Polyethylene wear and recurrent osteolysis of the greater trochanter was noted in one hip at the eight-year follow-up examination.Conclusions: Fractures of the greater trochanter associated with osteolytic lesions can be effectively treated with open reduction, internal fixation with wire, and allogeneic bone-grafting. [ABSTRACT FROM AUTHOR]

Background: A fracture of the greater trochanter through an osteolytic lesion may occur as a late complication after total hip arthroplasty. The optimal treatment for this difficult complication remains controversial. We have treated this problem with internal fixation and allogeneic bone-grafting at the time of revision of a loose acetabular component.Methods: We retrospectively reviewed the results of treatment of a fracture through an osteolytic lesion of the greater trochanter in nineteen patients seen from 1996 to 2002. All fractures were treated with morselized allogeneic bone grafts and wire fixation at the time of revision of a failed acetabular component. Postoperative care included the use of an abduction orthosis and protected weight-bearing for at least three months. Follow-up of all patients consisted of radiographic examinations and clinical evaluation with use of the Harris hip score.Results: At an average duration of 3.8 years after the revision, eighteen of the nineteen fractures had healed. The average time to healing was five months. The one treatment failure occurred in a patient who did not comply with the use of an abduction orthosis. The average Harris hip score for all patients improved from 32.5 points preoperatively to 91.2 points at the time of the latest follow-up. Polyethylene wear and recurrent osteolysis of the greater trochanter was noted in one hip at the eight-year follow-up examination.Conclusions: Fractures of the greater trochanter associated with osteolytic lesions can be effectively treated with open reduction, internal fixation with wire, and allogeneic bone-grafting. [ABSTRACT FROM AUTHOR]

Background: Although intra-articular treatment with hyaluronic acid (HA) for symptomatic osteoarthritis has become widely accepted in recent decades, the pattern of its use has seldom been reported. We have explored the epidemiology of intra-articular HA treatment in Taiwan by using the rich data source from nationwide insurance claims.Methods: Taiwan's National Health Insurance (NHI), which covers 97% of inhabitants, offers extensive hospitalisation and ambulatory care. We identified the beneficiaries aged 60 years and older who received intra-articular HA within the NHI during 2004. The number of visits in which HA was administered were analysed by patient's age and gender and by the physician's specialty and practice site.Results: Among the 73,410,777 ambulatory visits by 2,909,219 beneficiaries aged 60 years and older in 2004, 35,782 (1.2%) patients received intra-articular HA treatment in 205,012 (0.3%) visits. The highest prevalence of HA use was in the 70-79 year age group in both sexes. Women received intra-articular HA treatment more frequently than men in all age groups, especially in the 60-69 and 70-79 year groups (1.6% vs. 0.5%, 2.2% vs. 1.0%, respectively). Most intra-articular HA procedures were performed by orthopaedic surgeons (75.1%) and physical medicine and rehabilitation physicians (15.2%), and at metropolitan hospitals (34.5%) and local community hospitals (38.2%).Conclusion: One out of 100 older patients in Taiwan received intra-articular HA treatment for osteoarthritis of the knee during the course of the year. There were age-gender differences in use of HA treatment. The completion rate of this treatment in our study was high, and thus intra-articular HA might be a good alternative for patients for whom conventional treatment fails. Further research is needed to examine the age-gender differences in use of intra-articular HA in Taiwan. [ABSTRACT FROM AUTHOR]

We employed an untargeted proteo-metabolomic approach to profile circulating biomarkers in plasma samples from the I-Lan Longitudinal Aging Study, aiming to identify biomarkers and pathways associated with physio-cognitive decline syndrome (PCDS). In 115 propensity score-matched PCDS case-control pairs, pathway analyses implicated dysregulation of fatty acid metabolism and inflammation in PCDS pathogenesis. Sex-specific associations were observed, with disruptions in central carbon metabolism (elevated PKM, MDH1, and GAPDH; decreased MINPP1) and tyrosine metabolism (decreased MIF, DBH; increased thyroxine) characterizing in men. In contrast, perturbations in glutathione and phenylalanine metabolism, including increased ANPEP, GSTP1, and decreased pyroglutamic acid, were identified in women. Results suggest that dysregulated energy and redox homeostasis likely contribute to PCDS development. Notably, ANPEP, PKM, and MIF emerged as potential biomarkers, elucidating the muscle-brain crosstalk framework. Our findings provide insights into potential molecular mechanisms underlying PCDS and the muscle-brain crosstalk, marking progress toward elucidating biomarkers in the journey of healthy aging., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Elevated circulatory phosphate levels are linked to age-related muscle dysfunction, yet the mechanisms remain unclear. This study investigated the hypothesis that inflammation plays a role in connecting elevated phosphate levels to muscular dysfunction in middle-aged and older individuals and explored potential sex-based differences in these associations., Methods: The study, based on the I-Lan Longitudinal Aging Study Cohort, analyzed individuals' serum phosphate and hsCRP levels. Sex-specific analyses explored links between circulatory phosphate, inflammation, and muscle profiles (mass, handgrip strength, and walking speed). The study also examined potential mediation or synergistic effects of inflammation in the circulatory phosphate-muscle relationship., Results: The study included 2006 participants (mean age: 65.5 ± 6.5 years; 49.8 % men). Women exhibited higher circulatory phosphate levels than men. Linear analyses revealed that higher phosphate levels were significantly associated with weaker handgrip strength but not with reduced muscle mass in both men and women. In women, circulatory phosphate was not associated with inflammation (hsCRP levels), while in men, higher phosphate levels were significantly associated with higher hsCRP levels. In men, a synergistic effect was observed, where the combination of high hsCRP and elevated phosphate levels had a more pronounced impact on reducing handgrip strength than either factor alone., Conclusions: This study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, significantly impacts health outcomes in older adults. This review explores the evolving landscape of sarcopenia research, with a particular focus on its unique characteristics in Asian populations and emerging pharmaceutical interventions. Recent studies have revealed distinct patterns of muscle mass decline in Asian adults, particularly in women, challenging the universal application of global sarcopenia diagnostic criteria. The Asian Working Group for Sarcopenia has proposed region-specific diagnostic criteria, acknowledging these ethnic variations. Prevalence estimates of sarcopenia vary widely, ranging from 10% to 40% in community-dwelling older adults. For specific chronic conditions, the prevalence of sarcopenia is notably higher, reaching 35% for cardiovascular diseases and 24.5% for chronic kidney disease. Sarcopenia is strongly associated with various chronic conditions, increasing the risk of falls by 1.5 to 3 times and significantly increasing mortality risk by 29% to 51%. Current management strategies primarily involve resistance exercise and nutritional interventions, with a recommended daily protein intake of at least 1.2 g/kg to maintain muscle health. Pharmaceutical development has gained significant momentum, with over 20 compounds in various stages of clinical trials. These include myostatin inhibitors, selective androgen receptor modulators, ghrelin receptor agonists, mesenchymal stem cell therapy, and follistatin gene therapy. However, the unique dietary patterns, cultural contexts, and potentially distinct drug responses in Asian populations necessitate tailored interventions and Asia-specific clinical trials. Future directions include refining Asian-specific diagnostic criteria, conducting large-scale epidemiological studies across multiple Asian countries, developing culturally appropriate interventions, integrating sarcopenia management into chronic disease care, and advancing pharmaceutical research with a focus on Asian populations. In conclusion, sarcopenia emerges as a critical nexus in the aging process, intricately linked with multiple organ systems and chronic conditions, underscoring the imperative for its recognition as a cornerstone in person-centered care and the holistic management of age-related health challenges., Competing Interests: Conflicts of interest: Dr. Liang-Kung Chen, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article., (Copyright © 2024, the Chinese Medical Association.)

Introduction: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality., Methods: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1 ) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively., Results: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042)., Conclusions: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To evaluate the association between paternal metformin use and risk of congenital malformations in offspring., Design: Population based, cross national cohort study., Setting: Norway and Taiwan., Participants: 619 389 offspring with paternal data during the period of sperm development (three months before pregnancy) in the Norwegian cohort during 2010-21 and 2 563 812 in the Taiwanese cohort during 2004-18., Main Outcome Measures: The primary outcome was any congenital malformation, and the secondary outcome was organ specific malformations, classified according to the European surveillance of congenital anomalies guidelines. Relative risks were estimated with an unadjusted analysis and with analyses restricted to the cohort of men with type 2 diabetes mellitus and those using overlap propensity score weighting to control for severity of diabetes and other potential confounders. Sibling matched comparisons were conducted to account for genetic and lifestyle factors. Relative risk estimates for Norwegian and Taiwanese data were pooled using a random effects meta-analytical approach., Results: Paternal data on metformin use during the period of sperm development was available for 2075 (0.3%) offspring in Norway and 15 276 (0.6%) offspring in Taiwan. Among these offspring, 104 (5.0%) in Norway and 512 (3.4%) in Taiwan had congenital malformations. Increased risks of any congenital malformation associated with paternal metformin use were observed in the unadjusted analysis and attenuated with increasing control of confounding. The relative risks of any malformations with paternal metformin use were 1.29 (95% confidence interval 1.07 to 1.55) in Norway and 1.08 (0.99 to 1.17) in Taiwan in the unadjusted analysis and 1.20 (0.94 to 1.53) and 0.93 (0.80 to 1.07), respectively, in the analysis restricted to fathers with type 2 diabetes mellitus. In the overlap propensity score weighting analysis restricted to fathers with type 2 diabetes mellitus, the relative risks were 0.98 (0.72 to 1.33) in Norway and 0.87 (0.74 to 1.02) in Taiwan, resulting in a pooled estimate of 0.89 (0.77 to 1.03). No associations were observed between paternal metformin use and any organ specific malformations. These findings were consistent in sibling matched comparisons and sensitivity analyses., Conclusions: The findings suggest that paternal use of metformin during the period of sperm development is not associated with congenital malformations in offspring, including organ specific malformations. Metformin can therefore continue to be considered a suitable initial oral agent for managing glucose levels in men with type 2 diabetes mellitus who plan on having children., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this work was supported by the Norwegian Research Council and by the National Science and Technology Council of Taiwan; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. The authors had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To develop an intrinsic capacity (IC) score and to investigate the association between IC transition with overall and cause-specific mortality, incident disability and healthcare utilization., Design: Retrospective cohort study SETTING AND PARTICIPANTS: Data from 1852 respondents aged ≥ 65 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed., Measurements: Transitions of IC score were categorized into three groups: (1) Improved IC (IC 2003-1999 >0), (2) Stable IC (IC 2003-1999 = 0), (3) Worsened IC (IC 2003-1999 <0). Cox regression and subdistribution hazard models were used to investigate IC transitions and 4-year overall and cause-specific mortality, respectively. Logistic regression were employed to develop weighted IC score (wIC, 0-16) and assess its association with incident disability and healthcare utilization. Similar analysis were repeated using non-weighted IC (nIC, 0-8) to ensure robustness., Results: Comparing to decreased wIC group, stable or increased wIC participants had significantly lower 4-year all-cause mortality, and death from infection, cardiometabolic/cerebrovascular diseases, organ failure and other causes. (Hazard ratio (HR) ranged from 0.36 to 0.56, 95% CI ranged from 0.15 to 1.00, p ≤ 0.049 in the stable wIC group; HR ranged from 0.41 to 0.51, 95% CI ranged from 0.22 to 0.94, p ≤ 0.034 in the increased wIC group). Moreover, individuals with stable or increased wIC demonstrated lower risk of incident disability and hospitalization. (Odds ratio (OR) = ranged from 0.34 to 0.70, 95% CI ranged from 0.19 to 1.00, p ≤ 0.048). Participants with stable wIC also exhibited reduced risk of emergency department visits (OR = 0.58, 95% CI = 0.41 to 0.82, p = 0.002). These results were generally consistent in the nIC model., Conclusion: Participants with stable or increased IC experienced significantly lower all-cause and most cause-specific mortality, incident disability, and healthcare utilization, which was independent of baseline IC and comorbidities. The findings remained consistent across weighted and non-weighted IC model., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Limited knowledge exists regarding the interrelations between sleep quality and resilience within the demographic of healthy, community-residing middle-aged and older adults, with a particular dearth of information regarding sex-specific associations. This study aimed to examine the sex-specific associations between sleep quality, resilience, and biomarkers in community-dwelling middle-aged and older adults., Methods: This cross-sectional study was conducted using data from the 2022 Gan-Dau Healthy Longevity Plan survey initiated by the locality-based community hospital, Taipei Municipal Gan-Dau Hospital (TMGDH). A total of 770 participants (240 men, 530 women) who met the inclusion criteria were included in the study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while resilience was measured using the Brief Resilience Scale (BRS). Patient demographic data, including age, education, marital status, and depression level, were also collected. The sex-specific associations between sleep quality and resilience were first examined using multivariate generalized linear models (GLMs). In addition, the associations between sleep quality, resilience, and selected biomarkers were examined using multivariate GLMs., Results: Approximately 55% of men and 60% of women reported poor sleep quality. Individuals with good sleep quality had significantly lower levels of depressive symptoms (p=0.028 for men, p<0.001 for women) and fewer chronic conditions (p=0.0015 for men, p<0.001 for women). Notably, women in the "poor sleep quality" group exhibited higher proportions of low habitual sleep efficiency (35.9%) and frequent use of sleeping medications (23.2%), whereas the proportions were lower in men in the "poor sleep quality" group (29.8% and 9.9%, respectively). Good sleep quality was associated with better resilience in both men (mean BRS score: good sleep quality=25.1 [standard deviation (SD) 4.3] vs. poor sleep quality=23.4 [SD 4.7], p=0.044) and women (mean BRS score: good sleep quality=24.3 [SD 5.1] vs. poor sleep quality=22.3 [SD 5.4], p<0.001). After adjusting for depressive symptoms and chronic conditions, this association remained significant for men (p=0.022) and women (p=0.001). In addition, greater depressive symptoms were associated with poorer resilience in both sexes (p<0.001). No significant associations were noted between sleep quality or resilience and the selected biomarkers., Conclusion: This study highlights the association between sleep quality and resilience in older adults. Good sleep quality is related to better resilience, but greater depressive symptoms are also linked to poorer resilience in both sexes. Nevertheless, the low habitual sleep efficiency and frequent use of sleeping medications in women but not men with poor sleep quality highlight the need to explore sex-specific approaches to address the interplay of sleep quality, resilience and other demographic factors (such as depressive symptoms) in healthy aging., Competing Interests: Conflicts of interest: Dr. Liang-Kung Chen, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glucosamine (GlcN) is one of the dietary supplements used in the treatment of osteoarthritis. Endogenously, GlcN is synthesized from glucose through the hexosamine pathway. In addition to ameliorating arthritis, several biological functions of GlcN have been reported, including insulin resistance in skeletal muscle. However, the regulatory role of GlcN in skeletal muscle development is not clear. We therefore investigated the effect of GlcN on myoblast proliferation, differentiation, and myotube development and their underlying mechanisms in C2C12 cells. Myoblast proliferation was measured by MTT assay. The expressions of MyoD, myogenin (MyoG), and myosin heavy chain (MyHC) were identified as determinants of myoblast differentiation. Expressions of atrogin-1 and muscle RING-finger protein-1 (MuRF-1) were identified as markers of myotube atrophy. The results show that treatment with GlcN significantly reduced myoblast proliferation and phosphorylation of Stat3 and S6K. These findings suggest that GlcN can inhibit growth of myoblasts through inhibiting phosphorylation of Stat3 and S6K. In addition, GlcN significantly suppressed the expression of MyoD, MyoG, and MyHC, as well as myotube formation. Pretreatment of C2C12 myoblast cells with ER stress inhibitors significantly blocked GlcN-inhibited MyHC expression and myotube formation. It can be concluded that GlcN suppressed myogenic differentiation via a pathway that involved ER stress. Moreover, GlcN decreased myotube diameter and expression of MyHC, as well as increased MuRF-1 in C2C12 myotubes. Meanwhile, GlcN also reduced the expressions of phosphorylated Akt and mTOR were stimulated after GlcN treatment in C2C12 myotubes. Thus, GlcN induced skeletal muscle atrophy by inhibiting the protein synthesis pathway. Chronic GlcN infusion also caused skeletal muscle atrophy in mice. In conclusion, GlcN regulated important stages of skeletal muscle development through different signaling pathways., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study aims to develop an innovative approach for monitoring and assessing labor pain through ECG waveform analysis, utilizing machine learning techniques to monitor pain resulting from uterine contractions., Methods: The study was conducted at National Taiwan University Hospital between January and July 2020. We collected a dataset of 6010 ECG samples from women preparing for natural spontaneous delivery (NSD). The ECG data was used to develop an ECG waveform-based Nociception Monitoring Index (NoM). The dataset was divided into training (80%) and validation (20%) sets. Multiple machine learning models, including LightGBM, XGBoost, SnapLogisticRegression, and SnapDecisionTree, were developed and evaluated. Hyperparameter optimization was performed using grid search and five-fold cross-validation to enhance model performance., Results: The LightGBM model demonstrated superior performance with an AUC of 0.96 and an accuracy of 90%, making it the optimal model for monitoring labor pain based on ECG data. Other models, such as XGBoost and SnapLogisticRegression, also showed strong performance, with AUC values ranging from 0.88 to 0.95., Conclusions: This study demonstrates that the integration of machine learning algorithms with ECG data significantly enhances the accuracy and reliability of labor pain monitoring. Specifically, the LightGBM model exhibits exceptional precision and robustness in continuous pain monitoring during labor, with potential applicability extending to broader healthcare settings., Trial Registration: ClinicalTrials.gov Identifier: NCT04461704., (© 2024. The Author(s).)

Background: Paroxysmal Sympathetic Hyperactivity (PSH) occurs with high prevalence among critically ill Traumatic Brain Injury (TBI) patients and is associated with worse outcomes. The PSH-Assessment Measure (PSH-AM) consists of a Clinical Features Scale (CFS) and a Diagnosis Likelihood Tool (DLT), intended to quantify the severity of sympathetically-mediated symptoms and likelihood that they are due to PSH, respectively, on a daily basis. Here, we aim to identify and explore the value of dynamic trends in the evolution of sympathetic hyperactivity following acute TBI using elements of the PSH-AM., Methods: We performed an observational cohort study of 221 acute critically ill TBI patients for whom daily PSH-AM scores were calculated over the first 14 days of hospitalization. A principled group-based trajectory modeling approach using unsupervised K-means clustering was used to identify distinct patterns of CFS evolution within the cohort. We also evaluated the relationships between trajectory group membership and PSH diagnosis, as well as PSH DLT score, hospital discharge GCS, ICU and hospital length of stay, duration of mechanical ventilation, and mortality. Baseline clinical and demographic features predictive of trajectory group membership were analyzed using univariate screening and multivariate multinomial logistic regression., Results: We identified four distinct trajectory groups. Trajectory group membership was significantly associated with clinical outcomes including PSH diagnosis and DLT score, ICU length of stay, and duration of mechanical ventilation. Baseline features independently predictive of trajectory group membership included age and post-resuscitation motor GCS., Conclusions: This study adds to the sparse research characterizing the heterogeneous temporal trends of sympathetic nervous system activation during the acute phase following TBI. This may open avenues for early identification of at-risk patients to receive tailored interventions to limit secondary brain injury associated with autonomic dysfunction and thereby improve TBI patient outcomes.

Background: GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2 diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2 diabetes, with a specific focus on stratifying people by their frailty status., Methods: In this retrospective, nationwide, longitudinal study, we identified people (aged ≥20 years) with type 2 diabetes who newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017 to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1 year before the index date. Mortality data were collected from the Taiwan National Death Registry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model., Findings: We identified 320 210 people with type 2 diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57·7 years [SD 13·9], 11 338 [49·4%] were female, and 11 630 [50·6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58·8 years [12·3], 107 988 [42·0%] were female, and 149 207 [58·0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414 pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except for a higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than with SGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1·25 [95% CI 1·13-1·38]; p<0·0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2·43 [1·82-3·23]; p<0·0001), mild frailty (3·93 [3·03 -5·09]; p<0·0001), and moderate or severe frailty (2·60 [2·03-3·31]; p<0·0001) subgroups., Interpretation: Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2 diabetes., Funding: Ministry of Education, Taiwan., Competing Interests: Declaration of interests F-YH, EC-HT, and C-YW have received a research grant, awarded to the National Taiwan University, from Novo Nordisk. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to examine the longitudinal relationships between the trajectories of distinct subtypes of various domains of social supports and risk of subjective motoric cognitive risk (MCR) syndrome., Design: Longitudinal cohort study., Setting and Participants: 2,279 participants in the Taiwan Longitudinal Study on Aging (TLSA) between 1999 and 2011., Method: A group-based multi-trajectory modeling (GBMTM) was implemented to identify distinct trajectory subtypes within various social support domains, encompassing social networks, emotional support, instrumental support, as well as working and economic status. Logistic regression models were then utilized to evaluate the associations between these trajectory subtypes and the risk of subjective MCR., Results: Among 2,279 participants, GBMTM identified four distinct trajectory subtypes: "low social support" (n = 371), "medium social support " (n = 862), "high social support" (n = 292), and "high social support with employment" (n = 754). The incidence rates of subjective MCR for these groups were 9.4%, 9.0%, 4.1%, and 0.8%, respectively. After adjusting for age, sex, education level, and comorbidities, both "low social support" (adjusted odds ratio (aOR) 4.07, 95% CI [1.60-10.34]) and "medium social support" (aOR 3.10, 95% CI [1.26-7.66]) were significantly associated with an increased risk of subjective MCR compared to the "high social support with employment" group., Conclusions and Implications: The current study demonstrates that social support significantly reduces the risk of subjective MCR, with lower support levels correlating to higher risk, necessitating further intervention studies to confirm the link between social support and risk of subjective MCR., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Given the established association between sarcopenia and cognitive impairment was mainly in the older and oldest-old population or people with relatively limited education, this study extends the investigation to community-dwelling middle-to-old age adults in urban communities, emphasizing the need for preventive intervention for muscle health and healthy longevity., Methods: Data of 712 participants from the Gan-Dau Healthy Longevity Plan were retrieved for analysis, and all participants were stratified by age (50-64, 65-74 and 75+ years old). Possible sarcopenia was defined by 2019 consensus report of the Asian Working Group for Sarcopenia (AWGS). This study used four neuropsychological tests for analysis, i.e., Mini-Mental Status Examination (MMSE), California Verbal Learning Test II (CVLT-SF), Digital Symbol Substitution Test (DSST) and Verbal fluency (VF) for global and domain-specific cognitive function. Multivariate generalized linear models (GLMs) were employed to investigate the associations between possible sarcopenia and cognitive function in each age-specific groups., Results: The prevalence of possible sarcopenia increased with age, with 31.8 %, 37.7 %, and 55.6 % in participants aged 5064, 65-74 and, 75+ years, respectively. On the other hand, cognitive performance declined with age. In particular, among participants aged 75+ years with possible sarcopenia, their cognitive performance were poorer than robust counterparts, including MMSE (26.6 [3.4] vs. 27.4 [2.6]), CVTL-SF (total score: 21.5 [5.4] vs. 23.8 [5.5]; 30-second delayed recall: 6.0 [1.7] vs. 6.5 [1.6]), DSST (32.8 [14.3] vs. 41.3 [18.7]), and VF (12.8 [5.1] vs. 14.8 [4.9]). Multivariate generalized linear model indicated that possible sarcopenia was associated with lower MMSE (β: -0.70, p = 0.014) and lower DSST (β: -7.00, p = 0.010) in those aged 50-64 years. Moreover, possible sarcopenia was associated with lower CVLT-SF (total score β:-1.90, p = 0.028), lower DSST (β: -6.45, p < 0.001), and lower VF (β: -1.64, p=0.026) in 75+ years group., Conclusions: An association exists between possible sarcopenia and cognitive impairment, encompassing global cognition, delayed memory, verbal fluency, and executive function, among community-dwelling adults of mid-to-old age. Future research is warranted to explore the temporal alterations in this association and the potential effects of interventions aimed at fostering healthy longevity., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Blood pressure or flow measurements have been associated with vascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface., (© 2024. The Author(s).)

Background: Sarcopenia, characterized by age-related loss of muscle mass and function, poses a significant public health concern, particularly in Asia's rapidly aging population. This systematic review and meta-analysis aimed to evaluate the current epidemiology of sarcopenia in Asia using the 2019 Asian Working Group for Sarcopenia (AWGS) diagnostic criteria., Methods: Databases including PubMed, Embase, Web of Science, and Cochrane were systematically searched for studies published until December 7, 2023, involving older adults aged ≥ 60 years diagnosed with sarcopenia using the 2019 AWGS criteria in Asia. Study quality was assessed, and meta-analyses were conducted to estimate the pooled prevalence of sarcopenia, possible sarcopenia, and severe sarcopenia., Results: A total of 140 studies, collectively involving 156,325 participants (67.1 % community-dwelling older adults with the minimum age for participant inclusion ranging from 60 to 80 years) from various Asian countries, were included. The overall prevalence of sarcopenia among community-dwelling older adults was 16.5 % (95 % CI: 14.7 %-18.4 %). Notably, the prevalence of possible sarcopenia was higher at 28.7 % (95 % CI: 22.0 %-36.5 %), while severe sarcopenia had a lower prevalence of 4.4 % (95 % CI: 3.3 %-5.8 %). Subgroup analyses revealed variations in sarcopenia prevalence based on diagnostic modalities, ranging from 7.5 % (95 % CI: 6.0 %-9.4 %) for assessments using bioelectrical impedance analysis, handgrip strength, gait speed, chair stand and short physical performance battery, to 20.8 % (95 % CI: 18.9 %-23.0 %) when using dual-energy X-ray absorptiometry coupled with muscle strength and physical performance measures., Conclusion: This comprehensive systematic review and meta-analysis highlights the substantial burden of sarcopenia among older adults in Asia, underscoring the need for early identification and intervention strategies to mitigate its adverse consequences on public health., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The link between aging and pulmonary function decline is well-established, but the underlying mechanisms have yet to be fully revealed. Serum follistatin, a myokine implicated in muscle degeneration, may play a role in age-related pulmonary changes. This study aims to investigate the relationship between serum follistatin levels and pulmonary function decline in community-dwelling older adults, and evaluate their combined association with all-cause mortality., Research Design and Methods: This longitudinal cohort study utilized data from 751 participants aged ≥50 years in the I-Lan Longitudinal Aging Study between 2018-2019. Serum follistatin levels, spirometry results, demographic and clinical data were retrieved. Participants were stratified based on their follistatin levels. Survival curves and group comparisons based on follistatin levels and decline in peak expiratory flow (PEF) using Kaplan-Meier analysis and log-rank tests. Multivariate Cox proportional hazards models were further used to identify independent predictors of all-cause mortality during the 52-month follow-up., Results: Elevated follistatin levels significantly correlated with worse pulmonary function, particularly decreased PEF (p = 0.030). Kaplan-Meier analysis revealed the combination of elevated follistatin levels and decreased PEF was associated with increased risk of all-cause mortality (Log-rank p = 0.023). Cox proportional hazards models further identified that concurrent presence of higher follistatin levels and decreased PEF predicted higher risk of all-cause mortality (adjusted HR 3.58, 95% CI: 1.22-10.53, p = 0.020)., Conclusion: Higher serum follistatin levels correlate with decreased pulmonary function, specifically PEF decline, in community-dwelling older adults. Furthermore, the coexistence of elevated follistatin levels and decreased PEF was associated with risk of all-cause mortality. Follistatin may serve as a biomarker for pulmonary aging and related adverse outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake., Methods: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition., Results: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 μg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (β = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (β = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (β = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (β = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (β = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (β = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls., Conclusions: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)