Elevated meteorin-like protein from high-intensity interval training improves heart function via AMPK/HDAC4 pathway.

High-intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate-intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved. 50 HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterward, shRNA-containing adenovectors were injected into mice, yielding five groups: control, HF, HF + HIIT + scrambled shRNA, HF + HIIT + shMetrnl, and HF + Metrnl (HF + exogenous Metrnl). Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups. Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMPK in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning. HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.

Objective Ischemia, Subjective Angina, and Psychological Distress in Angina With No Obstructive Coronary Disease.

BACKGROUND: Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. METHODS AND RESULTS: A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). CONCLUSIONS: In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

A Comprehensive Assessment of the Chinese Version of the Duke Activity Status Index in Patients with Cardiovascular Diseases.

Background: Exercise capacity serves as a direct representation of cardiac function. The Duke Activity Status Index (DASI), a self-administered 12-item questionnaire, covers aspects of daily living, household tasks, sexual function, and physical activity. Although widely used to evaluate exercise capacity, its validation in Chinese cardiovascular disease (CVD) patients has not been thoroughly explored. Considering the significant cultural and lifestyle differences between China and Western countries, which may influence Chinese patients' comprehension and responses to DASI, our objective is to culturally adapt DASI for Chinese patients with CVD to ensure its precision in assessing exercise capacity. Methods: The cultural adaptation of the original DASI questionnaire into Chinese followed a rigorous process to ensure its validity, reliability, and sensitivity to Chinese CVD patients. The study included 107 outpatients diagnosed with CVD who completed the DASI and cardiopulmonary exercise testing (CPET). Cronbach's alpha, Spearman correlation, and factor analysis were utilized to test reliability and validity. Receiver operating characteristic (ROC) curve analysis was employed to assess the prognostic utility of the DASI. Results: Participants had a mean DASI score of 39.40 ± 10.75 and a peak oxygen uptake (Peak VO 2 ) of 19.53 ± 5.89 mL/min/kg. The Chinese version of the DASI exhibited satisfactory reliability and validity in CVD patients, with a Chronbach's alpha coefficient of 0.706. The DASI score demonstrated a moderate correlation with Peak VO 2 measured by CPET (r = 0.67, p < 0.001). Factor analysis yielded three factors, accounting for 56.76% of the total variance, with factor 1 contributing to 26.38% of the variance. ROC curve analysis demonstrated that the DASI exhibited discriminative utility in the identification of patients with improved long-term prognosis (p < 0.001). The ROC curve had an area of 0.788 [95% confidence interval (CI) = 0.704-0.871]. The DASI score ≥ 36.85 served as the optimal threshold for enhanced long-term prognosis, exhibiting a sensitivity of 0.80 and a specificity of 0.69. Conclusions: The culturally adapted DASI questionnaire is a straightforward and efficient tool for reasonably evaluating exercise capacity in Chinese CVD patients.

Long-term trends in lifestyle factors among respondents with dyslipidemia in the United States.

OBJECTIVES: To explore the long-term trends in unhealthy lifestyle factors and the risk sociodemographic subgroups among people with dyslipidemia. METHODS: Data extracted from the 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Lifestyle factors were smoking status, alcohol drinking, obesity, dietary quality, depression, physical activity, and sedentary behavior. A Joinpoint regression model was used to estimate trends in the log-transformed age-standardized prevalence. Multinomial logistic regression models adjusted for age, sex, and race/ethnicity were used to analyze subgroups by sociodemographic factors. RESULTS: Data for 33,680 respondents were extracted between 1999 and 2018. The prevalence of smoking and poor-quality diet decreased from 1999 to 2018 (P<0.001), while obesity significantly increased (P<0.001). The prevalence of depression marginally increased from 2005 to 2018 (P=0.074). We observed that non-Hispanic Black individuals, Hispanics, males, as well as those with lower family income-to-poverty ratios and education levels, unemployed individuals, or those lacking a spouse/live-in partner, were at elevated risk of unhealthy lifestyle factors when compared to the reference groups. CONCLUSIONS: Among NHANES respondents from 1999 to 2018 with dyslipidemia, significant reductions in the prevalence of current smoking and poor diet were observed, while the prevalence of obesity was markedly increased. There were sociodemographic differences in the management of lifestyle factors. Further initiatives to encourage people with dyslipidemia are required to reduce potential adverse outcomes.

Obstructive Sleep Apnea as a Key Contributor to Mental Stress-Induced Myocardial Ischemia in Female Angina Patients with No Obstructive Coronary Artery Disease.

Purpose: Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited. Patients and Methods: We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI. Results: There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (ß=1.226, OR = 3.408 (1.200-9.681), P = 0.021). Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.

Deep learning model to discriminate diverse infection types based on pairwise analysis of host gene expression.

Accurate detection of pathogens, particularly distinguishing between Gram-positive and Gram-negative bacteria, could improve disease treatment. Host gene expression can capture the immune system's response to infections caused by various pathogens. Here, we present a deep neural network model, bvnGPS2, which incorporates the attention mechanism based on a large-scale integrated host transcriptome dataset to precisely identify Gram-positive and Gram-negative bacterial infections as well as viral infections. We performed analysis of 4,949 blood samples across 40 cohorts from 10 countries using our previously designed omics data integration method, iPAGE, to select discriminant gene pairs and train the bvnGPS2. The performance of the model was evaluated on six independent cohorts comprising 374 samples. Overall, our deep neural network model shows robust capability to accurately identify specific infections, paving the way for precise medicine strategies in infection treatment and potentially also for identifying subtypes of other diseases.

A multimodal physiological and psychological dataset for human with mental stress induced myocardial ischemia.

Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored treatment strategies, yet public data scarcity hampers understanding. Given the higher incidence of both conditions in women, this study prospectively enrolled 80 female ANOCA and 39 age-matched female controls, subjecting them to three types of mental stress tasks. ECGs were continuously monitored across Rest, Stress, and Recover stages of the mental stress tasks, with PET/CT imaging during the Stress stage to evaluate myocardial perfusion. With PET/CT serving as the gold standard for MSIMI diagnosis, 35 of the 80 ANOCA patients were diagnosed as MSIMI. Using ECG variables from different stages of mental stress tasks, we developed five machine learning models to diagnose MSIMI. The results showed that ECG data from different stages provide valuable information for MSIMI classification. Additionally, the dataset encompassed demographic details, physiological, and blood sample test results of the patients. We anticipate this new dataset will significantly push further progress in ANOCA and MSIMI research.

Mental Stress-Induced Myocardial Ischemia Detected by Global Longitudinal Strain and Quantitative Myocardial Contrast Echocardiography in Women With Nonobstructive Coronary Artery Disease.

BACKGROUND: The utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow and MSIMI. METHODS: Seventy-two female patients ages 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA) and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. Mental stress-induced myocardial ischemia was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain, ß, and A × ß were obtained, and their trends during mental stress testing were observed. ΔGLS was defined as the ratio of difference between global longitudinal strain values at stress and rest to the rest data. ß reserve and A×ß reserve were respectively calculated. RESULTS: Thirty-two ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P < .01). For ANOCA patients with MSIMI, left ventricular GLS, ß, and A × ß declined to varied extents during mental stress testing compared with those without MSIMI and the controls (P < .05). Bland-Altman plots demonstrated good consistency between ß reserve and A × ß reserve output by the deep neural network model and iMCE software. Receiver operating characteristic curve analyses showed that ΔGLS, ß reserve, and A × ß reserve demonstrated favorable ability to predict MSIMI, especially the combination of A × ß reserve using iMCE analysis and ΔGLS (area under the curve, 0.94; sensitivity, 83%; specificity, 97%). CONCLUSIONS: Novel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated myocardial blood flow response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.

Perfluoroalkyl sulfonate induces cardiomyocyte apoptosis via endoplasmic reticulum stress activation and autophagy flux inhibition.

Perfluoroalkyl sulfonate (PFOS) is a commonly used chemical compound that often found in materials such as waterproofing agents, food packaging, and fire retardants. Known for its stability and persistence in the environment, PFOS can enter the human body through various pathways, including water and the food chain, raising concerns about its potential harm to human health. Previous studies have suggested a cardiac toxicity of PFOS, but the specific cellular mechanisms remained unclear. Here, by using AC16 cardiomyocyte as a model to investigate the molecular mechanisms potential the cardiac toxicity of PFOS. Our findings revealed that PFOS exposure reduced cell viability and induces apoptosis in human cardiomyocyte. Proteomic analysis and molecular biological techniques showed that the Endoplasmic Reticulum (ER) stress-related pathways were activated, while the cellular autophagy flux was inhibited in PFOS-exposed cells. Subsequently, we employed strategies such as autophagy activation and ER stress inhibition to alleviate the PFOS-induced apoptosis in AC16 cells. These results collectively suggest that PFOS-induced ER stress activation and autophagy flux inhibition contribute to cardiomyocyte apoptosis, providing new insights into the mechanisms of PFOS-induced cardiomyocyte toxicity.

Cardiac rehabilitation for elderly, weak patients who undergo transcatheter edge-to-edge repair: a case report.

Background: The positive role of rehabilitation programmes for some cardiac patient populations (e.g. coronary artery disease, heart failure, transcatheter aortic valve replacement, and heart transplantation) is now well-known. However, the feasibility and outcomes of rehabilitation, prior to or immediately after percutaneous mitral valve reconstruction, using a clamping procedure have been poorly reported, especially among frail elderly patients. Case summary: An 85-year-old woman with acute heart failure symptoms (New York Heart Association functional class III), who had acute myocardial infarction 3 months ago, was hospitalized. An ultrasound cardiogram showed severe mitral regurgitation, and after a multidisciplinary discussion, transcatheter edge-to-edge repair (TEER) was considered the safest treatment option. Even then, though, due to her poor health status, it was still too risky for the patient to undergo without significant prior preparation. Thus, we decided to begin pre- and post-surgery cardiac rehabilitation (CR) to prepare her for TEER, comprising medicinal, nutritional, and psychological support, as well as exercise and smoking cessation. After pre-operative assessment and rehabilitation, the patient underwent TEER, followed by post-operative reassessment, and continued rehabilitation. Discussion: Our case study demonstrates that CR, both pre- and post-TEER, aids in improving the conditions of elderly patients with poor health, to minimize their risk for developing TEER-related complications. This case provides one possible CR regimen for those patients.

Establishing thresholds of handgrip strength based on mortality using machine learning in a prospective cohort of Chinese population.

Background: The relative prognostic importance of handgrip strength (HGS) in comparison with other risk factors for mortality remains to be further clarified, and thresholds used for best identify high-risk individuals in health screening are not yet established. Using machine learning and nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), the study aimed to investigate the prognostic importance of HGS and establish sex-specific thresholds for health screening. Methods: A total of 6,762 participants from CHARLS were enrolled. A random forest model was built using 30 variables with all-cause mortality as outcome. SHapley Additive exPlanation values were applied to explain the model. Cox proportional hazard models and Harrell's C index change were used to validate the clinical importance of the thresholds. Results: Among the participants, 3,102 (45.9%) were men, and 622 (9.1%) case of death were documented follow-up period of 6.78 years. The random forest model identified HGS as the fifth important prognostic variable, with thresholds for identifying high-risk individuals were < 32 kg in men and < 19 kg in women. Low HGS were associated with all-cause mortality [HR (95% CI): 1.77 (1.49-2.11), p < 0.001]. The addition of HGS thresholds improved the predictive ability of an established office-based risk score (C-index change: 0.022, p < 0.001). Conclusion: On the basis of our thresholds, low HGS predicted all-cause mortality better than other risk factors and improved prediction of a traditional office-based risk score. These results reinforced the clinical utility of measurement of HGS in health screening.

Impact of cardiac rehabilitation on pre- and post-operative transcatheter aortic valve replacement prognoses.

Transcatheter aortic valve replacement (TAVR) is a relatively new treatment method for aortic stenosis (AS) and has been demonstrated to be suitable for patients with varying risk levels. Indeed, among high-risk patients, TAVR outcomes are comparable to, or even better, than that of the traditional surgical aortic valve replacement (SAVR) method. TAVR outcomes, with respect to post-surgical functional capacity and quality of life, have also been found to be improved, especially when combined with cardiac rehabilitation (CR). CR is a multidisciplinary system, which integrates cardiology with other medical disciplines, such as sports, nutritional, mind-body, and behavioral medicine. It entails the development of appropriate medication, exercise, and diet prescriptions, along with providing psychological support, ensuring the cessation of smoking, and developing risk factor management strategies for cardiovascular disease patients. However, even with CR being able to improve TAVR outcomes and reduce post-surgical mortality rates, it still has largely been underutilized in clinical settings. This article reviews the usage of CR during both pre-and postoperative periods for valvular diseases, and the factors involved in influencing subsequent patient prognoses, thereby providing a direction for subsequent research and clinical applications.

Neuro-11: a new questionnaire for the assessment of somatic symptom disorder in general hospitals.

Background: Somatic symptom disorder (SSD) commonly presents in general hospital settings, posing challenges for healthcare professionals lacking specialised psychiatric training. The Neuro-11 Neurosis Scale (Neuro-11) offers promise in screening and evaluating psychosomatic symptoms, comprising 11 concise items across three dimensions: somatic symptoms, negative emotions and adverse events. Prior research has validated the scale's reliability, validity and theoretical framework in somatoform disorders, indicating its potential as a valuable tool for SSD screening in general hospitals. Aims: This study aimed to establish the reliability, validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD. Through this comparative analysis, we aimed to validate the effectiveness and precision of the Neuro-11, enhancing its utility in clinical settings. Methods: Between November 2020 and December 2021, data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People's Hospital in China for various physical discomforts. The patients completed multiple questionnaires, including the Neuro-11, Short Form 36 Health Survey, Patient Health Questionnaire 15 items, Hamilton Anxiety Scale and Hamilton Depression Scale. Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD. Results: The Neuro-11 demonstrated strong content reliability and structural consistency, correlating significantly with internationally recognised and widely used questionnaires. Despite its brevity, the Neuro-11 exhibited significant correlations with other questionnaires. A test-retest analysis yielded a correlation coefficient of 1.00, Spearman-Brown coefficient of 0.64 and Cronbach's α coefficient of 0.72, indicating robust content reliability and internal consistency. Confirmatory factor analysis confirmed the validity of the three-dimensional structure (p<0.001, comparative fit index=0.94, Tucker-Lewis index=0.92, root mean square error of approximation=0.06, standardised root mean square residual=0.04). The threshold of the Neuro-11 is set at 10 points based on the maximum Youden's index from the receiver operating characteristic curve analysis. In terms of diagnostic efficacy, the Neuro-11 has an area under the curve of 0.67. Conclusions: (1) The Neuro-11 demonstrates robust associations with standard questionnaires, supporting its validity. It is applicable in general hospital settings, assessing somatic symptoms, negative emotions and adverse events. (2) The Neuro-11 exhibits strong content reliability and validity, accurately capturing the intended constructs. The three-dimensional structure demonstrates robust construct validity. (3) The threshold of the Neuro-11 is set at 10 points.

Prognosis value of EAS index in patients with obstructive coronary artery disease.

Background: EAS index is reported to be an adjunctive tool for risk stratification in addition to left ventricular ejection fraction (LVEF). This study aimed to verify the predictive value of EAS index among coronary artery disease (CAD) patients with different cardiac systolic function levels. Methods: A total of 477 patients with obstructive CAD were included in the exploratory analysis of a prospective cohort between October 2017 and January 2018 at Guangdong Provincial People's Hospital. EAS index, e'/(a' × s'), is a novel parameter assessed by tissue Doppler imaging (TDI) indicating combined diastolic and systolic performance. Any occurrence of major adverse cardiovascular event (MACE) was recorded, including first onset of myocardial infarction, stroke, readmission for heart failure, coronary revascularization, or cardiovascular death that occurred within 6 months of the first admission. Kaplan-Meier survival and Cox regression analyses were applied to testify the predictive value of EAS index for cardiovascular outcome. Results: A total of 415 patients (87.2%) completed the follow-up (median, 25.9 months) and experienced 101 (24.3%) MACEs, 17 (4.0%) deaths, and 139 (33.4%) composite events. Elevated EAS index was significantly associated with a higher incidence of MACE, even after adjustment for age, sex, body mass index, N-terminal pro brain natriuretic peptide, high-sensitivity troponin T, high-density lipoprotein, stenosis degree, and other TDI parameters [Model 3, hazard ratio: 1.81, 95% confidence interval (CI): 1.15-2.85]. For different levels of cardiac function, Kaplan-Meier survival analysis revealed that elevated EAS index was associated with higher MACE incidence only in patients with LVEF ≥50% (P<0.05). Conclusions: EAS index is an independent predictor of MACE in patients with obstructive CAD, which could be utilized as a tool for risk stratification in CAD patients or incorporated into a prediction model to improve efficacy.

Physical activity attenuates the association between blood cadmium exposure and cardiovascular disease: findings from the National Health and Nutrition Examination Survey 2007-2018.

Existing studies could not separate the effects of heavy metal exposure on cardiovascular disease (CVD) risk from those caused by physical activity (PA). The possible interactive effect of heavy metal exposure and PA on the risk of CVD remains still unknown. We enrolled a total of 12,280 participants in 2007-2018 cycles of the U.S. National Health and Nutrition Examination Survey (NHANES) and discovered that both low blood concentrations of Cd and Pb were positively correlated with increased prevalence of CVD and subtypes, with a stronger association for blood Cd than Pb. Negative dose-response relationships between PA and the prevalence of CVD and subtypes were identified. Participants with inactive and active PA had lower risk of CVD than those having no PA, with multivariate adjusted ORs 0.8 (95% CI: 0.69, 0.94) and 0.76 (95% CI: 0.68, 0.85), respectively. The only evidence for negative interaction between regular PA and blood Cd concentrations was found with regard to the prevalence of CVD and subtypes, indicating that regular PA could well modify the adverse effect of blood Cd on CVD risk. We demonstrate for the first time to date that PA may have a beneficial effect against the hazardous impact of Cd exposure on elevated CVD risk, emphasizing the necessity to promote a healthy lifestyle with active PA.

Trends in unhealthy lifestyle factors in US NHANES respondents with cardiovascular disease for the period between 1999 and 2018.

Objectives: To examine national trends in unhealthy lifestyle factors among adults with cardiovascular disease (CVD) in the United States (US) between 1999 and 2018. Methods: We analyzed data from National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of participants with CVD who were aged ≥20 years, which was conducted between 1999 and 2000 and 2017-2018. CVD was defined as a self-report of congestive heart failure, coronary heart disease, angina, heart attack, or stroke. The prevalence rate of each unhealthy lifestyle factor was calculated among adults with CVD for each of the 2-year cycle surveys. Regression analyses were used to assess the impact of sociodemographic characteristics (age, sex, race/ethnicity, family income, education level, marital status, and employment status). Results: The final sample included 5610 NHANES respondents with CVD. The prevalence rate of their current smoking status remained stable among respondents with CVD between 1999 and 2000 and 2017-2018. During the same period, there was a decreasing trend in the age-adjusted prevalence rate of poor diet [primary American Heart Association (AHA) score <20; 47.5% (37.9%-57.0%) to 37.5% (25.7%-49.3%), p < 0.01]. Physical inactivity marginally increased before decreasing, with no statistical significance. The prevalence rate of sedentary behavior increased from 2007 to 2014 but subsequently returned to its original level in 2018 with no statistical significance. The age-adjusted prevalence rate of obesity increased from 32% (27.2%-36.8%) in 1999-2000 to 47.9% (39.9%-55.8%) in 2017-2018 (p < 0.001). The age-adjusted prevalence rate of depression increased from 7% (4.2%-9.9%) in 1999-2000 to 13.9% (10.2%-17.6%) in 2017-2018 (p = 0.056). Trends in mean for each unhealthy lifestyle factor were similar after adjustment for age. We found that respondents who had low education and income levels were at a higher risk of being exposed to unhealthy lifestyle factors (i.e., smoking, poor diet, and physical inactivity) than those who had high education and income levels. Conclusions: There is a significant reduction in the prevalence rate of poor diet among US adults with CVD between 1999 and 2018, while the prevalence rate of obesity showed increasing trends over this period. The prevalence rate of current smoking status, sedentary behavior, and depression was either stable or showed an insignificant increase. These findings suggest that there is an urgent need for health policy interventions targeting unhealthy lifestyles among adults with CVD.

Joint Associations of Device-Measured Sleep Duration and Efficiency With All-Cause and Cause-Specific Mortality: A Prospective Cohort Study of 90 398 UK Biobank Participants.

BACKGROUND: Both sleep duration and efficiency are essential for health outcomes. However, few studies have considered the effects of both sleep duration and efficiency on predicting the risks of mortality. This study investigated the independent and joint associations of accelerometer-measured sleep duration and efficiency with all-cause and cause-specific mortality. METHODS: The UK Biobank is a cohort study of over 500 000 individuals recruited between 2006 and 2010. This study included participants wearing wrist accelerometers for 7 consecutive days between February 2013 and December 2015. Mortality was ascertained by the national death registries. RESULTS: Of the 90 398 participants (age, 62.4 [7.8] years, 43.5% male) who were included, 2 685 deaths were reported within a median follow-up duration of 6.4 years. Both accelerometer-measured short (adjusted hazard ratios, 1.27; 95% confidence interval [CI]: 1.11-1.45) and long sleep duration (adjusted hazard ratios, 1.16; 95% CI: 1.06-1.28) were positively associated with the risks of all-cause mortality. Lower sleep efficiency was associated with an increased risk of all-cause and cause-specific mortality. Significant interaction existed between accelerometer-measured sleep duration and efficiency for the risk of all-cause mortality (Pinteraction = .001), participants with long sleep duration and lower sleep efficiency had a double mortality risk compared with those with higher sleep efficiency and normal sleep duration (adjusted hazard ratios = 2.11; 95% CI: 1.44-3.09). CONCLUSIONS: Accelerometer-measured short/long sleep duration and lower sleep efficiency were associated with increased risks of mortality. Sleep efficiency modified the effects of long sleep duration on survival.

The alterations in multiple neurophysiological procedures are associated with frailty phenotype in older adults.

Background: Older adults oftentimes suffer from the conditions in multiple physiologic systems, interfering with their daily function and thus contributing to physical frailty. The contributions of such multisystem conditions to physical frailty have not been well characterized. Methods: In this study, 442 (mean age = 71.4 ± 8.1 years, 235 women) participants completed the assessment of frailty syndromes, including unintentional weight loss, exhaustion, slowness, low activity, and weakness, and were categorized into frail (≥3 conditions), pre-frail (1 or 2 conditions), and robust (no condition) status. Multisystem conditions including cardiovascular diseases, vascular function, hypertension, diabetes, sleep disorders, sarcopenia, cognitive impairment, and chronic pain were assessed. Structural equation modeling examined the interrelationships between these conditions and their associations with frailty syndromes. Results: Fifty (11.3%) participants were frail, 212 (48.0%) were pre-frail, and 180 (40.7%) were robust. We observed that worse vascular function was directly associated with higher risk of slowness [standardized coefficient (SC) = -0.419, p < 0.001], weakness (SC = -0.367, p < 0.001), and exhaustion (SC = -0.347, p < 0.001). Sarcopenia was associated with both slowness (SC = 0.132, p = 0.011) and weakness (SC = 0.217, p = 0.001). Chronic pain, poor sleep quality, and cognitive impairment were associated with exhaustion (SC = 0.263, p < 0.001; SC = 0.143, p = 0.016; SC = 0.178, p = 0.004, respectively). The multinomial logistic regression showed that greater number of these conditions were associated with increased probability of being frail (odds ratio>1.23, p < 0.032). Conclusion: These findings in this pilot study provide novel insights into how multisystem conditions are associated with each other and with frailty in older adults. Future longitudinal studies are warranted to explore how the changes in these health conditions alter frailty status.

Single-nucleus RNA sequencing unveils critical regulators in various hippocampal neurons for anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuropsychiatric disease with variable clinical manifestations caused by NMDAR autoantibody. The underlying molecular underpinnings of this disease are rarely characterized on a genomic scale. Anti-NMDAR encephalitis mainly affects the hippocampus, however, its effect on gene expression in hippocampal neurons is unclear at present. Here, we construct the active and passive immunization mouse models of anti-NMDAR encephalitis, and use single-nucleus RNA sequencing to investigate the diverse expression profile of neuronal populations isolated from different hippocampal regions. Dramatic changes in cell proportions and differentially expressed genes were observed in excitatory neurons of the dentate gyrus (DG) subregion. In addition, we found that ATP metabolism and biosynthetic regulators related genes in excitatory neurons of DG subregion were significantly affected. Kcnq1ot1 in inhibitory neurons and Meg3 in interneurons also changed. Notably, the latter two molecules exhibited opposite changes in different models. Therefore, the above genes were used as potential targets for further research on the pathological process of anti-NMDAR encephalitis. These data involve various hippocampal neurons, which delineate a framework for understanding the hippocampal neuronal circuit and the potential molecular mechanisms of anti-NMDAR encephalitis.