[Association between plasma selenium and the risk of impaired glucose regulation].

Objective: To investigate the association between plasma selenium exposure and the risk of impaired glucose regulation (IGR). Methods: A case-control study was conducted to select IGR patients who were admitted to the outpatient clinic of the Department of Endocrinology to perform oral glucose tolerance test(OGTT) at the Tongji Hospital affiliated to the Tongji Medical College from September 2004 to 2016 as a case group. Participants with normal glucose tolerance recruited from an unselected group of population undergoing routine health examinations in the same hospital were selected as a control group. The control group was matched according to the age (±5 years old) and sex of the case group. The inclusion criteria for subjects recruited were as follows: age ≥30 years, body mass index (BMI) <40 kg/m(2), no history of a diagnosis of IGR or type 2 diabetes, and no history of receiving pharmacological treatment for hyperlipidemia or hypertension. Patients with any clinically systemic disease such as neurological or endocrine disease, acute illness, chronic inflammatory disease or infectious disease were excluded from the study. A total of 1 957 subjects, 897 in the case group and 1 060 in the control group, were included. Questionnaires were used to collect information of all subjects, and peripheral venous blood was collected after fasting and OGTT, respectively. Plasma selenium, fasting blood glucose, blood lipid (total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol) and 2 h OGTT plasma glucose concentration were detected, respectively. The subjects were divided into low, medium and high concentration groups according to the tertiles of plasma selenium concentration in the control group. The multivariate unconditional logistic regression analysis was performed to analyze the association between plasma selenium exposure and IGR. Results: The age (mean±SD) of the case and control group was (53.71±11.38) and (53.95±12.17) years old. The plasma selenium concentration [M (P(25), P(75))] in the case group was 92.81(77.07, 107.05) µg/L, which was significantly higher than the control group [88.73 (77.13, 100.88) µg/L] (P<0.05). The results of multivariate unconditional logistic regression analysis showed that after adjusting for age, sex, BMI, family history of diabetes and hypertension, the risk of IGR was higher in the high-concentration group and the low-concentration group compared with the middle-concentration group, the values of OR (95%CI) were 1.22 (95%CI: 0.94-1.59) and 1.81 (95%CI: 1.42-2.30), respectively. Conclusion: The study suggested a U-shaped association between plasma selenium and IGR.

Fentanyl-induced cough is a risk factor for postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) and fentanyl-induced cough (FIC) are two common anaesthesia-related events, which seem to have common risk factors. In this prospective cohort study, we investigate whether patients who have FIC during induction of anaesthesia have an increased incidence of PONV. METHODS: We studied adult non-smoking gynaecological surgical patients enrolled between July 1, 2011 and July 30, 2012. The presence of FIC during induction and the occurrence of PONV were recorded. Fentanyl-induced cough and other perioperative variables were subjected to multivariate analysis to determine the association between FIC and PONV. RESULTS: All 502 patients enrolled in this study had at least two risk factors for PONV, and 154 (31%) developed FIC. The incidence of PONV in the FIC group was higher than in the non-FIC group (56.5 vs 38.2%; P<0.0001). Multivariate logistic regression analysis found FIC to be a predictive risk factor for the development of PONV (adjusted odds ratio 2.08, 95% confidence interval 1.41-3.07). CONCLUSIONS: Non-smoking women undergoing gynaecological surgery who develop FIC during induction of anaesthesia have a higher incidence of PONV.

Time caliper method with enhanced accuracy using an arbitrary waveform generator and time demultiplexer with fine clock offset.

An improved time caliper method has been proposed for measuring a small relative delay of two signals transmitted on different channels. This is achieved by using a new method to generate two periodic pulse trains that have much smaller period difference, over 1000 times smaller than that in the prior scheme. The two pulse trains, with a period difference of 0.1 ps, are generated by an arbitrary waveform generator and a time demultiplexer, with a fine clock offset. The average and maximum measurement errors obtained are 0.68 and 1.67 ps, respectively.

Effect of cervical artificial disc replacement on adjacent inferior intervertebral space stress.

PURPOSE: The aim of this study was to investigate the effects of C5/6 cervical artificial disc replacement (CADR), discectomy and intervertebral fusion on adjacent inferior (C6/7) intervertebral space stress, and provide a basis for application of CADR. METHODS: Eleven fresh-frozen multisegmental (C3-T1) cervical spine specimens from healthy adults were studied. For analysis of stress on the adjacent inferior (C5/6) segment, they were divided into intact group, discectomy group, CADR group and interbody fusion group. The axial load (25-150 N) was exerted on each group. The changes of the adjacent inferior (C6/7) intervertebral space stress were observed. RESULTS: The adjacent inferior intervertebral space stress in the CADR group was near to that of the intact group, without significant difference (p > 0.05). The stress in the discectomy group was significantly higher than in the intact group, and lower than in the interbody fusion group (p < 0.05 and p < 0.01, respectively). The stress in the interbody fusion group was significantly higher than in the intact and CADR groups, respectively (p < 0.01).

Dose-Responsive Impacts of Social Frailty on Intrinsic Capacity and Healthy Aging among Community-Dwelling Middle-aged and Older Adults: Stronger Roles of Social Determinants over Biomarkers.

OBJECTIVE: The intricate relationship between social determinants, e.g., social frailty, biomarkers and healthy aging remains largely unexplored, despite the potential for social frailty to impact both intrinsic capacity (IC) and functional ability in the aging process. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: Participants aged 50+ years from the Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan, stratified into three age groups: 50-64, 65-74 and 75+. MEASUREMENTS: Social frailty was defined based on a score derived from four domains: exclusion from general resources, social resources, social activity, and fulfillment of basic social needs. The scores were categorized as score=0 (no social frailty), 1 (social pre-frailty), and 2+ (social frailty). Multivariable logistic regression and Cox proportional hazard models were employed to examine the dose-responsive relationship between social frailty, low IC, functional and psychological health, and mortality. RESULTS: Of 1015 study participants, 24.9% and 7.9% were classified as social pre-frailty and social frailty, respectively. No significant differences were observed in most biomarkers between those with social frailty and those without. A dose-responsive relationship was found between social frailty and increased risk of low IC (social pre-frailty: aOR 2.20 [95% CI 1.59-3.04]; social frailty: 5.73 [3.39-9.69]). Similar results were found for functional and psychological health. However, no significant association between social frailty and all-cause mortality was found at the 4-year follow-up (social pre-frailty: aHR 1.52 [95% CI 0.94-2.43]; social frailty: 1.59 [0.81-3.09]). CONCLUSIONS: The significant association between social frailty and low IC, functional limitations, cognitive declines, and depressive symptoms underscores the pressing need for research on intervention strategies to enhance healthy aging in the lifespan course.

Roles of Baseline Intrinsic Capacity and its Subdomains on the Overall Efficacy of Multidomain Intervention in Promoting Healthy Aging among Community-Dwelling Older Adults: Analysis from a Nationwide Cluster-Randomized Controlled Trial.

BACKGROUND: Impaired intrinsic capacity (IC), which affects approximately 90% of older adults, is associated with a significantly heightened risk of frailty and cognitive decline. Existing evidence suggests that multidomain interventions have the potential to enhance cognitive performance and yield positive effects on physical frailty. OBJECTIVE: To examine roles of baseline IC and its subdomains on the efficacy of multidomain interventions in promoting healthy aging in older adults. DESIGN: a cluster-randomized controlled trial. SETTING AND PARTICIPANTS: 1,054 community-dwelling older adults from 40 community-based clusters across Taiwan. INTERVENTION: A 12-month pragmatic multidomain intervention of exercise, cognitive training, nutritional counseling and chronic condition management. MEASUREMENTS: Baseline IC was measured by 5 subdomains, including cognition (Montreal Cognitive Assessment, MoCA), sensory (visual and hearing impairment), vitality (handgrip strength or Mini-Nutritional Assessment-short form), psychological well-being (Geriatric Depression Scale-5), and locomotion (6m gait speed). Outcomes of interest were cognitive performance (MoCA scores) and physical frailty (CHS frailty score) over a follow-up period of 6 and 12 months. RESULTS: Of all participants (mean age:75.1±6.4 years, 68.6% female), about 90% participants had IC impairment at baseline (2.0±1.2 subdomains). After covariate adjustment using a generalized linear mixed model (GLMM), the multidomain intervention significantly prevented cognitive declines and physical frailty, particularly in those with IC impairment ≥ 3 subdomains (MoCA: coefficient: 1.909, 95% CI: 0.736 ~ 3.083; CHS frailty scores: coefficient = -0.405, 95% CI: -0.715 ~ -0.095). To assess the associations between baseline poor capacity in each IC subdomain and MoCA/CHS frailty scores over follow-up, a 3-way interaction terms (time*intervention*each poorer IC subdomains) were added to GLMM models. Significant improvements in MoCA scores were shown for participants with poorer baseline cognition (coefficient= 1.138, 95% CI: 0.080 ~ 2.195) and vitality domains (coefficient= 1.651, 95% CI: 0.541 ~ 2.760). The poor vitality domain also had a significant modulating effect on the reduction of CHS frailty score after the 6- and 12-month intervention period (6 months: coefficient= -0.311, 95% CI: -0.554 ~ -0.068; 12 months: coefficient= -0.257, 95% CI: -0.513 ~ -0.001). CONCLUSION AND IMPLICATIONS: A multidomain intervention in community-dwelling older adults improves cognitive decline and physical frailty, with its effectiveness influenced by baseline IC, highlighting the importance of personalized strategies for healthy aging.

Untangling the Complex Interplay between Social Isolation, Anorexia, Sarcopenia, and Mortality: Insights from a Longitudinal Study.

BACKGROUND: Social isolation is a pervasive and debilitating condition that has adverse prognostic impacts. This condition often co-occurs with other geriatric syndromes, further exacerbating negative health outcomes. Given these considerations, the present study aims to elucidate the roles of social isolation in older adults with anorexia of aging and/or sarcopenia with respect to long-term mortality using a nationally representative cohort study. METHODS: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with a sample size of 3,762 study participants aged 50 years and older. Data from 1999 (wave 4) to 2015 (wave 9) were analyzed. The TLSA questionnaire was used to define social isolation, anorexia, and sarcopenia. Logistic regressions were employed to explore the associations between social isolation, anorexia, and sarcopenia. The Cox proportional hazard model was utilized to examine the synergistic effects of social isolation and anorexia or sarcopenia on 16-year all-cause mortality. RESULTS: After controlling for demographic information and comorbidities, older adults with social isolation were significantly associated with anorexia (adjusted odds ratio [aOR] 1.46 [95% confidence interval: 1.00-2.12, p=0.0475]) and sarcopenia (aOR 1.35 [95% CI: 1.12-1.64, p=0.0021]). Furthermore, the synergistic effects of social isolation with anorexia (aOR 1.65 [95% CI: 1.25-2.18, p=0.0004]) or sarcopenia (aOR 1.65 [95% CI: 1.42-1.92, p<0.0001]) were both significantly associated with higher risks of all-cause mortality, while social isolation alone revealed borderline statistical significance. CONCLUSIONS: Our findings indicate that social isolation is closely linked to anorexia and sarcopenia among middle-aged and older adults. Additionally, social isolation significantly exacerbates the long-term mortality risk associated with anorexia of aging and sarcopenia. However, social isolation alone appears to have borderline long-term mortality risk in this cohort. These findings underscore the importance of addressing social isolation in older adults with anorexia and/or sarcopenia to optimize their health outcomes and mitigate long-term mortality risk.

Age- and Sex-Different Associations between Cognitive Performance and Inflammatory Biomarkers in Community Dwelling Older Adults: towards Precision Preventive Strategies.

BACKGROUND: Studies have demonstrated associations between inflammatory biomarkers and cognitive function in people with dementia or stroke, but little is known regarding these associations in healthy middle-aged and older populations. OBJECTIVES: This study aims to examine associations between inflammatory biomarkers (both vascular and systemic) and cognitive performance in stroke- and dementia-free middle-aged and older adults without apolipoprotein E4 (ApoE ε4) allele carriers. DESIGN: A cross-sectional study. SETTING: Social Environment and Biomarkers of Aging Study (SEBAS) 2006. PARTICIPANTS: A total of 983 participants aged 53 years and older. MEASUREMENTS: Composite cognitive function assessment, including the Short Portable Mental Status Questionnaire, the Rey Auditory Verbal Learning Test, and the Wechsler Adult Intelligence Scale. Overnight venous blood sampling for 6 inflammatory biomarkers (C-reactive protein, interleukin-6, fibrinogen, homocysteine, intercellular adhesion molecule-1 and E-selectin) and ApoE genotyping. RESULTS: Among 983 participants (mean age: 65.8±9.5 years), 808 were non-ApoE e4 allele carriers and were stroke- and dementia-free. Higher log fibrinogen was associated with poorer cognitive function after adjustment for potential confounding factors in non-ApoE e4 allele carriers and stroke- and dementia-free populations (unstandardized coefficients ß= -1.553, P value= 0.003). In participants aged 65 years or older, both of elevated fibrinogen and homocysteine were associated with poorer cognitive function (ß= -2.288, P value= 0.015; ß= -1.331, P value= 0.012, respectively). Elevated log CRP was significantly associated with lower cognitive function only in women (ß= -0.514, P value= 0.024). CONCLUSION: Higher serum levels of fibrinogen were negatively associated with cognitive function, which was independent of ApoE genotyping and prior cerebrovascular events in dementia-free community-dwelling older adults. Further studies are needed to validate the roles of fibrinogen in the pathophysiology of dementia and elucidate the underlying mechanisms.

Cardiovascular Disease Risk Burden, Cognitive Impairments and Incident Dementia among Community-Dwelling Middle-Aged and Older Adults: An 8-Year Longitudinal Follow-up Study.

OBJECTIVES: To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up. DESIGN: A community-based longitudinal cohort study. SETTING: Yuanshan township in Yi-Lan County, Taiwan. PARTICIPANTS: A total of 889 community-dwelling residents aged 50 years or older. MEASUREMENTS: Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test. RESULTS: Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 [95% confidence interval (CI) 1.19-2.15], P=0.002), verbal memory (aOR 1.97 [1.43-2.70], P< 0.001) and language (aOR 1.99 [1.46-2.70], P< 0.001), as well as incident dementia (aOR 2.40 [1.33-4.33], P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment. CONCLUSIONS: Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment.

Comparative Analysis of Intrinsic Capacity Impairments, Determinants, and Clinical Consequences in Older Community-Dwellers in Japan and Taiwan: Longitudinal Studies Showing Shared Traits and Distinct Presentations.

OBJECTIVES: Despite the recognized impact of intrinsic capacity (IC) impairment on healthy aging, international comparisons in different sociocultural contexts are scarce. This study aimed to compare IC impairment among community-dwelling older adults in Japan and Taiwan to explore the context of healthy aging in different countries. DESIGN: Comparative observational study. SETTING: National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan and Longitudinal Aging Study of Taipei (LAST) in Taiwan. PARTICIPANTS: 794 individuals (age range, 60.0-86.5 years) from NILS-LSA and 1,358 (60.0-96.7 years) from LAST. MEASUREMENTS: IC impairment was evaluated across the domains of locomotion, cognition, vitality, sensory capacity, and psychological well-being. Participants were categorized as having impaired IC or healthy. We investigated associations between IC impairment, falls, and all-cause mortality. RESULTS: IC impairment was present in 54.9% and 37.3% of participants in the NILS-LSA and LAST cohorts, respectively. Male NILS-LSA participants with impaired IC (odds ratio [OR]:1.50, 95% confidence interval [CI]:1.03-2.20), with hearing loss (OR:1.98, 95% CI:1.00-3.90) were more likely to fall. In LAST, impaired locomotion (OR:2.14, 95% CI:1.46-3.14) increased the risk of falls. Men with impaired IC (hazard ratio [HR]; 2.14, 95% CI:1.10-4.15) and visual impairment (HR:2.21, 95% CI:1.15-4.25) and women with impaired psychological well-being (HR:4.94, 95% CI:1.28-18.97) in the NILS-LSA cohort had greater risk for all-cause mortality; however, this was not shown for LAST participants. CONCLUSION: The prevalence and distribution of IC impairment and associated biomarkers differed significantly between participants in Japan and Taiwan. However, the associations with adverse outcomes remained similar, emphasizing the need for tailored interventions for healthy aging.

Long-Term Mortality Risk in Older Adults with Sarcopenia: An 11-Year Prospective Cohort Study Comparing AWGS 2014 and AWGS 2019 Guidelines for Enhanced Clinical Utility and Accurate Risk Prediction.

OBJECTIVES: To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines. DESIGN: A prospective population-based cohort study. SETTING AND PARTICIPANTS: The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022. MEASUREMENTS: We utilized a handgrip strength dynamometer to measure participants' muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria. RESULTS: The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04-2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality. CONCLUSION: AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk.

Risk factors for developing pain in normospermic patients with varicocoele.

To assess the possible risk factors for developing pain in normospermic adult varicocoele patients, 42 adult patients with left painful varicocoele (group 1) and 35 age-matched patients with left painless varicocoele (group 2) were recruited to this study. All the patients had normal semen quality (spermatozoa density, motility and morphology). Pain score on a 10-cm visual analogue scale was used to assess the scrotal pain as a result of varicocoele. The severity of pain was defined as follows: mild pain (1-3 cm), moderate pain (4-6 cm) and severe pain (7-10 cm). The parameters for comparison included body mass index (BMI), the distance from the renal hilum to scrotum (DRS), semen quality and pH value, serum concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, alkaline phosphatase (Alk-p), lactate dehydrogenase (LDH), testicular volume and discrepancy (%), grade of varicocoele and peak retrograde flow (PRF) and spontaneous venous reflux (SVR) by colour Doppler ultrasound and scrotal temperature (ST). The mean ages were 27.8 and 27.1 years old in groups 1 and 2, respectively. By multivariate analysis, patients in group 1 had significantly higher PRF, ST, DRS and rate of SVR, and lower BMI than those in group 2. Furthermore, there were significant differences in PRF, DRS and BMI among patients in group 1 with different degrees of pain. Conclusively, normospermic adult patients with left painful varicocoele had significantly higher peak retrograde flow, ST, distance from the renal hilum to scrotum, and rate of spontaneous venous reflux and lower BMI than those with left painless varicocoele. Furthermore, varicocoele patients with severe pain had significantly higher peak retrograde flow and distance from the renal hilum to scrotum, and lower BMI than those with moderate and mild pain.

Detection of patients presenting with adverse drug events in the emergency department.

BACKGROUND: Adverse drug events (ADE) have been studied widely in hospitalised and emergency department (ED) patients. Less is known about the ED visits of drug-related injury in Taiwan. This study seeks to determine the incidence, risk and patient outcomes of ADE in an ED population. METHODS: We conducted a prospective observational cohort study of patients 18 years and older presenting to the ED of an urban, tertiary medical centre. ED visits between 1 March 2009 and 28 February 2010 identified by investigators for suspected ADE were further assessed by using the Naranjo Adverse Drug Reaction probability scale. Outcomes (ED disposition, injury severity and preventability) and associated variables (triage, gender, drug category, number of drugs, Charlson comorbidity index score and ADE mechanism) were measured. RESULTS: Of 58,569 ED visits, 452 patients (0.77%) had physician-documented ADE. 24% of patients with ADE were hospitalised with life-threatening conditions, with a mortality rate of 10.0%. The majority of ADE were considered preventable (73.4%), and the unintentional overdose was the most common cause. Cardiovascular agents accounted for the most ADE (25.8%) and consisted of 65.3% of ADE in patients aged 65,years and older. Risk factors for ADE-related hospitalisation were elderly age (odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.4), severity of ADE (OR 6.9, 95% CI 3.3-14.5) and higher Charlson comorbidity index scores (OR 3.4, 95% CI 2.0-5.7). CONCLUSION: ADE-related ED visits are not uncommon in Taiwan and many cases are preventable. ED-based surveillance may provide useful information for monitoring outpatient ADE.

Clinical Efficacy of Multidomain Interventions among Multimorbid Older People Stratified by the Status of Physio-Cognitive Declines: A Secondary Analysis from the Randomized Controlled Trial for Healthy Aging.

OBJECTIVES: To investigate the clinical efficacy of integrated multidomain intervention among community-living older adults with multimorbidity and physio-cognitive decline syndrome (PCDS). DESIGN, SETTING AND PARTICIPANTS: This is the secondary analysis from a randomized controlled trial that data of 340 participants with Montreal Cognitive Assessment (MoCA) scores≥18 were excerpted for analysis. INTERVENTION: Sixteen 2-hour sessions per year were provided for participants, including physical exercise, cognitive training, dietician education and individualized integrated care for multimorbidity. MEASUREMENTS: Handgrip strength, 6-m walking speed, MoCA (total score and sub-domains), Cardiovascular Health Study (CHS) frailty score, quality of life, and serum biochemistry biomarkers. RESULTS: Overall, 96/340 (28.2%) of all participants have PCDS, and the integrated multidomain intervention significantly improved global cognitive performance (overall difference 1.1, 95% CI 0.4 - 1.8, p=0.003), and domains of concentration (overall difference 0.3, 95%CI 0.1 - 0.5, p=0.011), language (overall difference 0.2, 95%CI 0.1 - 0.3, p=0.006), abstract thinking (overall difference 0.1, 95%CI 0.0 - 0.3, p=0.027), and orientation(overall difference 0.2, 95%CI 0.0 - 0.4, p=0.013) across all timepoints among those with PCDS. Besides, interventions also significantly reduced frailty score among those with cognitive impairment no dementia (overall difference -0.3, 95%CI -0.5 - -0.1, p=0.011) and mobility impairment no disability (overall difference -0.3, 95%CI -0.4 - -0.1, p=0.004). and improved quality of life at domain of physical role limitation among those with PCDS (overall difference 5.3, 95%CI 0.3 - 10.4, p=0.038). CONCLUSIONS: The integrated multidomain lifestyle intervention plus multimorbidity management significantly improved cognitive function, and enhanced quality of life among older adults with multimorbidity and PCDS in the communities.

Intrinsic Capacity Impairment Patterns and their Associations with Unfavorable Medication Utilization: A Nationwide Population-Based Study of 37,993 Community-Dwelling Older Adults.

OBJECTIVES: Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study. DESIGN: A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020. SETTING AND PARTICIPANTS: The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach. METHODS: Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models. RESULTS: Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The "depression with cognitive impairment" group (EPP: aOR=4.35, 95% CI 3.52-5.39, p<0.01; PIMs: aOR=2.73, 95% CI 2.46-3.02, p<0.01) and the "impairment in all domains" group (EPP: aOR=9.02, 95% CI 7.16-11.37, p<0.01; PIMs: aOR=3.75, 95% CI 3.24-4.34, p<0.01) remained at higher odds for EPP and PIMs after adjustment. CONCLUSIONS: We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the "depression with cognitive impairment" and "impairment in all domains", was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility.

Oral Nutritional Supplement with ß-hydroxy-ß-methylbutyrate (HMB) Improves Nutrition, Physical Performance and Ameliorates Intramuscular Adiposity in Pre-Frail Older Adults: A Randomized Controlled Trial.

OBJECTIVES: Supplementation of high protein oral nutrition shakes supplemented with ß-hydroxy-ß-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons. METHODS: This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity. RESULTS: Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs -22.9±309.1 mm2 for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. -0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. -1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m2, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (-0.38±1.21 vs. -0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (ß=0.71, 95% C.I.0.09-1.33, P=0.026). CONCLUSIONS: The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.

Physio-Cognitive Decline Syndrome as the Phenotype and Treatment Target of Unhealthy Aging.

In this era of unprecedented longevity, healthy aging is an important public health priority. Avoiding or shortening the period of disability or dementia before death is critical to achieving the defining objectives of healthy aging, namely to develop and maintain functional capabilities that enable wellbeing in older age. The first step is to identify people who are at risk and then to implement effective primary interventions. Geriatricians have identified a distinct clinical phenotype of concurrent physical frailty and cognitive impairment, which predicts high risk of incident dementia and disability and is potentially reversible. Differing operational definitions for this phenotype include "cognitive frailty", "motoric cognitive risk syndrome" and the recently proposed "physio-cognitive decline syndrome (PCDS)". PCDS is defined as concurrent mobility impairment no disability (MIND: slow gait or/and weak handgrip) and cognitive impairment no dementia (CIND: ≥1.5 SD below the mean for age-, sex-, and education-matched norms in any cognitive domain but without dementia). By these criteria, PCDS has a prevalence of 10-15% among community-dwelling older persons without dementia or disability, who are at increased risk for incident disability (HR 3.9, 95% CI 3.0-5.1), incident dementia (HR 3.4, 95% CI 2.4-5.0) and all-cause mortality (HR 6.7, 95% CI 1.8-26.1). Moreover, PCDS is associated with characteristic neuroanatomic changes in the cerebellum and hippocampus, and their neurocircuitry, which are distinct from neuroimaging features in normal aging and common dementia syndromes. Basic research and longitudinal clinical studies also implicate a hypothetical muscle-brain axis in the pathoetiology of PCDS. Most important, community-dwelling elders with PCDS who participated in a multidomain intervention had significant improvements in global cognitive function, and especially in the subdomains of naming and concentration. Our proposed operational definition of PCDS successfully identifies an appreciable population of at-risk older people, establishes a distinct phenotype with an apparently unique pathoetiology, and is potentially reversible. We now need further studies to elucidate the pathophysiology of PCDS, to validate neuroimaging features and muscle-secreted microRNA biomarkers, and to evaluate the effectiveness of sustained multidomain interventions.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Detection of T cell receptor alpha chain locus rearrangements in human antigen-specific T lymphocyte clones using a DNA probe specific for chromosome region 14q11.

Human cloned antigen-specific T lymphocytes were used to characterize DNA rearrangements using a cDNA probe from the T cell receptor (TCR)-alpha chain gene. Rearranged patterns were detected in some T cell clones, confirming that normal mature T cells are rearranged in TCR-alpha locus. Similarly, rearranged DNA patterns were found in T cell clones from the same panel, using a DNA probe (clone K-40, [1]) isolated from chromosome 14 (14q11), where the TCR-alpha locus has been mapped. These results suggest that this genomic DNA clone is located within the TCR-alpha chain locus.

Helper cell-independent cytotoxic clones in man.

We report here a class of helper cell-independent cytotoxic T cell (HITc) clones in man that can proliferate in response to antigenic stimulation as well as mediate cytotoxicity. HITc appear to be rare among clones derived from primary in vitro allosensitized culture, but constitute the majority of clones derived from cells sensitized to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines. The implications of the derivation and function of HITc clones are discussed.