Gender and Age Differences in the Evaluation and Clinical Outcomes of Patients with Palpitations.

BACKGROUND: Palpitations represent a common clinic complaint. OBJECTIVE: To explore gender and age differences in the evaluation and outcomes of patients with palpitations in outpatient settings. DESIGN/PARTICIPANTS: This is a retrospective observational study of 58,543 patients with no known structural cardiac disease or arrythmias presenting to primary care and cardiology clinics in an integrated health system in California with palpitations between January 2017 and December 2021. The primary and secondary endpoints were hospitalization for arrhythmia and all-cause mortality at 1 year. Multivariable logistic regression models evaluated the association between gender, age, and outcomes. RESULTS: Men and women were equally as likely to be started on beta-blockers (adjusted OR 0.96, 95% CI 0.90-1.02) and evaluated with electrocardiograms (adjusted OR 0.95, 95% CI 0.90-1.01) and cardiac monitors (adjusted OR 1.04, 95% CI 0.99-1.08). Patients who completed Holter or event monitors had a lower rate of hospitalization for cardiovascular disease at 1 year than those without (2.3% vs. 2.7%, p = 0.001). At 1 year, women had a lower risk of all-cause mortality (adjusted OR 0.47, 95% CI 0.35-0.64) and hospitalization for atrial fibrillation (adjusted OR 0.47, 95% CI 0.30-0.72) and arrhythmias (adjusted OR 0.73, 95% CI 0.58-0.91) compared to men. Among older women and men (≥ 80 years), there was no significant difference in 1-year all-cause mortality (adjusted OR 0.57, 95% CI 0.29-1.12), hospitalization for atrial fibrillation (adjusted OR 0.58, 95% CI 0.17-1.97), or arrhythmias (adjusted OR 1.15, 95% CI 0.12-11.07). CONCLUSIONS: There were no gender differences in referrals for cardiac monitoring or prescriptions for beta-blockers. Women had a better prognosis with a lower risk of hospitalization for arrhythmias and death at 1 year compared to men. However, 1-year risks for mortality and hospitalization for arrythmias among older women were comparable to those of older men, underscoring the importance of considering age and gender in managing patients with palpitations.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Assessing intrinsic capacity in Taiwan: Initial psychometric properties of the Integrated Care for Older People Screening Tool for Taiwanese (ICOPES-TW).

BACKGROUND: The World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW). METHODS: Older people (n = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]). RESULTS: The ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach's α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age (r = 0.321), IADL (r = 0.313), and frailty (r = 0.601), and (ii) negatively correlated with QoL (r=-0.447), and BADL (r=-0.447), with all p-values < 0.001. CONCLUSION: The ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

Secondary Amine Catalysis in Enzyme Design: Broadening Protein Template Diversity through Genetic Code Expansion.

Secondary amines, due to their reactivity, can transform protein templates into catalytically active entities, accelerating the development of artificial enzymes. However, existing methods, predominantly reliant on modified ligands or N-terminal prolines, impose significant limitations on template selection. In this study, genetic code expansion was used to break this boundary, enabling secondary amines to be incorporated into alternative proteins and positions of choice. Pyrrolysine analogues carrying different secondary amines could be incorporated into superfolder green fluorescent protein (sfGFP), multidrug-binding LmrR and nucleotide-binding dihydrofolate reductase (DHFR). Notably, the analogue containing a D-proline moiety demonstrated both proteolytic stability and catalytic activity, conferring LmrR and DHFR with the desired transfer hydrogenation activity. While the LmrR variants were confined to the biomimetic 1-benzyl-1,4-dihydronicotinamide (BNAH) as the hydride source, the optimal DHFR variant favorably used the pro-R hydride from NADPH for stereoselective reactions (e.r. up to 92 : 8), highlighting that a switch of protein template could broaden the nucleophile option for catalysis. Owing to the cofactor compatibility, the DHFR-based secondary amine catalysis could be integrated into an enzymatic recycling scheme. This established method shows substantial potential in enzyme design, applicable from studies on enzyme evolution to the development of new biocatalysts.

Association between Epstein-Barr virus infection and serum positivity rate of anti-nuclear antibodies in Chongqing, China: A cross-sectional observational study.

Epstein-Barr virus (EBV) infects over 95% of the global population and is strongly associated with various autoimmune diseases. Anti-nuclear antibodies (ANA) serve as valuable laboratory biomarkers for screening and supporting the diagnosis of various autoimmune diseases. The aim of this study was to assess the prevalence of EBV infection and its association with ANA. This retrospective study employed standard indirect immunofluorescence assay to determine ANA levels, EBV-specific immunofluorescence assay, or plasma EBV-DNA testing. Demographic data including gender and age were collected to observe variations in EBV infection status and ANA positivity rates among different populations. Incorporating 6492 hospitalized patients who underwent ANA antibody spectrum testing, it was observed that serum positivity rates gradually increased with age. The overall serum positivity rate of ANA in females (25.14%) was significantly higher than that in males (13.76%). Among hospitalized patients undergoing EBV-DNA testing, adults aged 21 to 40 years were least affected by EBV, with a positivity rate of 11.96%; however, as age increased, the positivity rate gradually increased. Among the 5225 patients undergoing EBV antibody spectrum testing, ANA-positive patients exhibited significantly higher serum positivity rates for Epstein-Barr nuclear antigen 1 immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin A, and Epstein-Barr virus viral capsid antigen immunoglobulin A antibodies compared to ANA-negative patients (P < .001; P < .001; P = .013; P < .001). The EBV-DNA positivity rate in ANA-positive patients was also significantly higher than in ANA-negative patients, yielding the same conclusion (P = .012). The positivity rates of ANA antibodies in patients with past EBV infection and reactivation were significantly higher than those in uninfected patients (P < .001; P = .006). The positivity rate of ANA antibodies in reactivated patients was significantly higher than that in primary infected patients and those with past infections (P < .001; P < .001). Among ANA-positive patients, the positivity rates of EBV antibody spectrum and EBV-DNA were higher compared to ANA-negative patients. The positivity rates of ANA in patients with past EBV infection and reactivation were higher than those in uninfected patients.

Prognostic Value of Stress Myocardial Perfusion Imaging Across the Spectrum of Cardiovascular Risk.

BACKGROUND: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used to identify ischemia. There is limited research to evaluate if there is a risk threshold below which SPECT-MPI may not add significant prognostic value. METHODS: Between January 1, 2012, and December 31, 2018, individuals who underwent SPECT-MPI were stratified into 4 risk groups. The primary outcome was acute myocardial infarction (MI) or death. Multivariable Cox proportional hazards regression analysis was used to calculated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 48,845 patients (52.3% male, median age 67 years), 8.5% were low risk, 4.8% borderline risk, 18.1% intermediate risk, and 68.6% high risk based on the American College of Cardiology pooled cohort equation. Ischemia was more commonly detected in the high-risk cohort (19.4% in high-risk vs 6.5% in low-risk). SPECT-MPI testing was associated with a significantly increased use of preventive medications such as statin therapy, regardless of stress test results. At a median follow-up of 4.2 years, there was no significant association between ischemia and death or MI in the low-risk cohort (adjusted HR, 1.91; 95% CI, 0.94-3.92) or the borderline-risk cohort (adjusted HR, 1.58; 95% CI, 0.79-3.15). Ischemia was associated with a higher risk of death or MI in the intermediate-risk (adjusted HR, 1.57; 95% CI, 1.24-1.99) and high-risk groups (adjusted HR, 1.54; 95% CI, 1.44-1.64). CONCLUSIONS: SPECT-MPI was less useful for risk stratification among low-risk patients because of their low event rates regardless of test results.

Racial and Ethnic Differences in the Prevalence of Severe Aortic Stenosis by Echocardiography.

BACKGROUND: Understanding the burden of aortic stenosis (AS) across diverse racial and ethnic populations is important to ensure equitable resource allocation. This study explored whether severe AS rate varies by race and ethnicity. METHODS: The rates of severe AS, stratified by race and ethnicity, were calculated among 615,038 adults with a transthoracic echocardiogram. Logistic regression analysis was performed to identify factors associated with severe AS. RESULTS: Severe AS rates ranged from 0.08% in adults < 50 years old to 3.8% in those ≥ 90 years old. Compared to non-Hispanic White and Asian American [adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI): 0.42-0.53] and non-Hispanic Black (aOR = 0.44, 95% CI: 0.39-0.50) patients were less likely to have severe AS, whereas Hispanic patients (aOR = 0.91, 95% CI: 0.87-0.98) had near similar likelihood. Age was the strongest risk factor for severe AS (compared to age < 50 years, aOR = 21.8, 95% CI: 17.8-26.6 for age 80-89 years, and aOR = 43.8, 95% 35.5-54.0 for age ≥ 90 years). Additional factors associated with severe AS included male sex (aOR = 1.38, 95% CI: 1.30-1.46) and diabetes (aOR = 1.23, 95% CI: 1.15-1.31). CONCLUSIONS: Asian American and non-Hispanic Black adults had lower rates of severe AS compared to White and Hispanic patients. The rate of severe AS progressively increases with age in all racial and ethnic groups, with higher rates in men compared with women. With a demographic shift toward an aging and more diverse population, the burden of AS is anticipated to rise. Ensuring adequate allocation of resources to meet the evolving needs of a diverse population remains a shared health care imperative.

Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection typically presents with fever and respiratory symptoms, which can progress to severe respiratory distress syndrome and multiple organ failure. In severe cases, these complications may even lead to death. One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response. Therefore, suppressing the overactive immune response may be an effective strategy for treating COVID-19. Mesenchymal stem cells (MSCs) and their derived exosomes (MSCs-Exo) have potent homing abilities, immunomodulatory functions, regenerative repair, and antifibrotic effects, promising an effective tool in treating COVID-19. In this paper, we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19. We also summarize relevant recent clinical trials, including the source of cells, the dosage and the efficacy, and the clinical value and problems in this field, providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

The impact of sleep disturbances on suicide risk among people living HIV: An eleven-year national cohort.

OBJECTIVES: The suicide rate among individuals who experience sleep disturbances is five times higher than in the general population. Up to 70 % of people living with HIV (PLHIV) experience sleep disturbances. This study's purpose was to determine whether this population has higher rates of suicide compared to those without sleep disorders. Possible risk factors were also explored. METHODS: A secondary analysis of nationwide data on all males and females over 15 years old with HIV living in Taiwan was conducted from January 1, 2005, to December 31, 2016. Sleep disturbances were identified through recorded diagnoses and medical treatments. Cox proportional hazard models and hazard ratios (HRs) and mediation analysis were employed to estimate the association between sleep disturbances and suicide risk during the follow-up period. RESULTS: Of the 5680 PLHIV, 72 suicide events were reported. The suicide incidence rate among PLHIV suffering from sleep disturbances was 769 per 100,000 person-years. Sleep disturbances were associated with a significantly increased risk of suicide (AHR = 1.75, 95 % CI 1.02-3.02, p = 0.0429). A premium-based monthly salary of <24,000 (NT $) was also associated with an increased hazard of suicide (AHR = 4.14, 95 % CI 1.60-10.75, p = 0.0035). The pathway effect analysis using potential outcomes showed that depression did not mediate the effect of sleep disturbance on suicide. CONCLUSIONS: Sleep disturbances were associated with higher suicide rates, even after adjusting for pre-existing depression. These findings suggest that paying attention to suicidal ideation among PLHIV suffering from sleep disturbances is necessary.

Association of intrinsic capacity and medication non-adherence among older adults with non-communicable diseases in Taiwan.

OBJECTIVES: Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study aimed to examine the association of medication non-adherence with level of overall intrinsic capacity (IC), pattern of IC, and specific IC component among older adults with NCDs. METHODS: A cross-sectional questionnaire-based survey of 1268 older adults aged 60 years and above was conducted in 2022 in southern Taiwan. Among them, 894 suffered from 1 more NCD were included in this study. The Integrated Care for Older People Screening Tool for Taiwanese and the Adherence to Refills and Medication Scale were used to assess IC and medication non-adherence, respectively. Latent class analysis (LCA) was used to identify patterns of IC impairment, and binary logistic regression was used to assess the association between medication non-adherence and IC. RESULTS: Older adults in the moderate (score: 1-2) or low (score≧3) overall IC groups were more likely to experience medication non-adherence (moderate: adjusted odds ratio (aOR) 1.57 [95% CI: 1.05-2.36]; low: 2.26 [1.40-3.67]). The "physical and nutritional impairments accompanied by depressive symptoms" group was associated with statistically higher odds of medication non-adherence (aOR 1.66 [1.01-2.73]). Older adults with cognitive impairment, hearing loss, or depressive symptoms showed greater likelihood of medication non-adherence (cognitive impairment: aOR 1.53 [1.03-2.27]; hearing loss: aOR 1.57 [1.03-2.37]; depressive symptoms: aOR 1.81 [1.17-2.80]). CONCLUSIONS: Intervention for improving medication non-adherence among older adults with NCDs should consider IC.

Emergency Department Cardiac Risk Stratification With High-Sensitivity vs Conventional Troponin HEART Pathway.

Importance: Patients presenting to the emergency department with chest pain are routinely risk stratified for major adverse cardiac events using the HEART (History, Electrocardiogram, Age, Risk factors, and Troponin) score pathway, which incorporates clinical features, risk factors, electrocardiography findings, and initial serum troponin testing. A new HEART pathway incorporating high-sensitivity troponin level may improve risk stratification among patients with possible acute myocardial infarction (AMI). Objective: To compare health outcomes and resource use among emergency department patients undergoing cardiac risk stratification with a HEART pathway using conventional vs high-sensitivity serum troponin. Design, Setting, and Participants: This multicenter pre-post cohort study was conducted between January 1 and September 6, 2021, at 16 Kaiser Permanente Southern California hospitals during uptake of a high-sensitivity serum troponin assay and included 17 384 adult patients who presented to an emergency department with chest pain and were risk stratified with a HEART pathway based on conventional troponin or high-sensitivity troponin. Exposures: A HEART pathway incorporating either conventional or high-sensitivity serum troponin was used to stratify study groups for risk of major adverse cardiac events within 30 days. Main Outcomes and Measures: The primary outcome was detection of AMI in the emergency department and within 30 days. Results: Of the 17 384 patients (median age, 58 years [IQR, 45-69 years]; 9767 women [56.2%]), 12 440 (71.6%) were risk stratified with a HEART pathway based on conventional troponin, and 4944 (28.4%) were risk stratified with a HEART pathway based on high-sensitivity troponin. Detection of AMI within 30 days was higher for the high-sensitivity troponin group than the conventional troponin group (288 [5.8%] vs 545 [4.4%]; P < .001), while the 30-day all-cause mortality rate was unchanged (16 [0.3%] vs 50 [0.4%]; P = .50). In the emergency department, 228 of 4944 patients (4.6%) in the high-sensitivity troponin group received a diagnosis of AMI compared with 251 of 12 440 patients (2.0%) in the conventional troponin group (P < .001). Among those who did not receive a diagnosis of AMI in the emergency department, an additional 60 patients (1.2%) in the high-sensitivity troponin group and 294 (2.4%) in the conventional troponin group (P < .001) received a diagnosis within 30 days. Patients in the high-sensitivity troponin group had lower rates of health care use compared with the conventional troponin group, including admission (605 [12.2%] vs 1862 [15.0%]; P < .001), stress testing within 7 days (506 [10.2%] vs 1591 [12.8%]; P < .001), and coronary revascularization within 30 days (51 [1.0%] vs 244 [2.0%]; P < .001). Conclusions and Relevance: This multicenter pre-post cohort study suggests that a new HEART pathway incorporating high-sensitivity troponin may improve detection of AMI and decrease resource use among emergency department patients with chest pain.