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Hsing-Yi Chang,1,2 Hsin-Ling Fang,1 Te-Tien Ting,3 Jersey Liang,4 Shao-Yuan Chuang,1 Chih-Cheng Hsu,1 Chin-Yin Wu,5 Wen-Harn Pan1,2,6 1Institute of Population Health Sciences, National Health Research Institutes, Maoli, Taiwan; 2Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; 3School of Big Data Management, Soochow University, Taipei, Taiwan; 4Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 5Institute of Sociology, Academia Sinica, Taipei, Taiwan; 6Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanCorrespondence: Hsing-Yi ChangInstitute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, A3223, Zhunan Town, Maoli County, ROC 35053, TaiwanTel +886 37 246166Fax +886 37 586261Email hsingyi@nhri.org.twPurpose: The co-occurrence of frailty and depression in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality have rarely been investigated. We aimed to examine the co-occurrence of frailty and depressive symptoms in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality using all the information from a longitudinal study.Patients and methods: We used the Taiwan Longitudinal Study of Aging (TLSA) for this study. TLSA was initiated in 1989 and followed periodically. We included participants from 1989 to 2007, who had data on frailty and depressive symptoms. Frailty was assessed by accumulation of functional deficits in 6 dimensions including disease status, sensory dysfunction, balance, functional limitations, health risk behaviors, and life satisfaction. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). A multistate model with interval censoring was used to examine the transition between states of frailty with or without depressive symptoms, and finally to death. A mixed model was used to examine the relationships between frailty and depressive symptoms.Results: The coexistence of frailty and depressive symptoms was associated with higher mortality. Individuals with depressive symptom had a lower probability of reversal to a better state. Previous depression score predicted current frailty, but the coefficient was smaller than that of previous frailty. Previous frailty predicted current depression score, and the coefficient was stronger than that of previous depression.Conclusion: Depressive symptoms increased the mortality and decreased the probability of reversal in the frail older adults.Keywords: TLSA, cumulative functional deficits, depressive symptom, multistate model, mortality

Background: To determine whether separate anthropometric screening tools are needed for obesity and the metabolic syndrome in children, we compared the predictability of several anthropometric indices, including waist circumference (WC) and body mass index (BMI), with regard to metabolic disorders. Study design: The Nutrition and Health Survey in Taiwan Elementary School Children (2000-2001) collected data from 2,215 children. Logistic regression analysis was used to study the association between anthropometric indices and metabolic abnormalities, which was defined as two or more of the following conditions: high fasting triglycerides, high fasting glucose levels, high blood pressure and low high-density lipoprotein-cholesterol. The receiver operating characteristic curve was used to study the sensitivity and specificity of these anthropometric indices. Results: predictability was the ranked highest for WC (R2 = 10.69%), followed by BMI (R2 = 9.80%), arm girth (R2 = 9.75%), hip circumference (R2 = 9.43%), scapular skinfold thickness (R2 = 9.28%) and waist-to-height ratio (R2 = 9.25%). Waist circumference or BMI cut-offs for maximal balanced sensitivity and specificity were close to the 60th percentile for each age and gender group. Values were greater in boys than in girls and increased with age. Conclusion: It is justifiable to use the WC criteria to define the metabolic syndrome in children. Due to its practicality, BMI remains the most suitable index for defining overweight/obesity. Only moderate levels of sensitivity and specificity were achieved with these two popular obesity indices with regard to metabolic abnormalities. [ABSTRACT FROM AUTHOR]

BACKGROUND.: A community-based study was conducted to investigate summer-winter differences of component of metabolic syndrome in Kinmen, Taiwan. METHODS.: A total of 8251 residents aged 40 and over were enrolled in the mass survey in Kinmen. They were investigated while on summer (July and August) and winter vacation (January and February) during 2000-2003. Demographics, physical examination findings, lifestyle variables and biochemical data were collected. RESULTS.: After controlling for age, body mass index, diet, lifestyle and other risk factors for component of metabolic syndrome, there were independent and significant relationships between summer-winter difference and component of metabolic syndrome. Winter season was positively correlated with blood pressure, fasting plasma glucose level, high-density lipoprotein-cholesterol (HDL-C) and waist circumference, but was negatively associated with fasting triglycerides and metabolic syndrome. CONCLUSIONS.: Summer season is positively associated with hypertriglyceridemia, low HDL-C and metabolic syndrome. These findings imply that cross-sectional, experimental and cohort studies of component of metabolic syndrome or metabolic syndrome should take season into account as possible confounding effects. Copyright © 2006 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

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

Background: Type 2 diabetes mellitus (T2DM) is increasingly being diagnosed in older adults. Our objective is to assess the advantages and potential drawbacks of different glucose-lowering medications in this specific population., Methods: A network meta-analysis was conducted to identify randomized controlled trials that examined patient-centered outcomes in adults aged ≥65 years with T2DM. We searched PubMed, Cochrane CENTRAL, and Embase up to September 23, 2023. Quality of eligible studies were assessed using the Cochrane RoB 2.0 tool., Results: A total of 22 trials that involved 41 654 participants were included, incorporating sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, sulfonylureas (SU) and acarbose. Our findings reveal that GLP-1RAs reduce the risk of major adverse cardiovascular events (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.71 to 0.97) and body weight (mean difference [MD], -3.87 kg; 95% CI, -5.54 to -2.21). SGLT2 inhibitors prevent hospitalization for heart failure (RR, 0.66; 95% CI, 0.57 to 0.77), renal composite outcome (RR, 0.69; 95% CI, 0.53 to 0.89), and reduce body weights (MD, -1.85 kg; 95% CI, -2.42 to -1.27). SU treatment increases the risk of any hypoglycaemia (RR, 4.19; 95% CI, 3.52 to 4.99) and severe hypoglycaemia (RR, 7.06; 95% CI, 3.03 to 16.43). GLP-1RAs, SGLT2 inhibitors, metformin, SU and DPP-4 inhibitors are effective in reducing glycaemic parameters. Notably, the number of treatments needed decreases in most cases as age increases., Conclusions: Novel glucose-lowering medications with benefits that outweigh risks should be prioritized for older patients with diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study examined the associations between pulse pressure, hypertension, and the decline in physical function in a prospective framework., Study Design: The Healthy Aging Longitudinal Study tracked a group of Taiwanese adults aged 55 or more over an average of 6.19 years to assess pulse pressure and decline in physical function, including in handgrip strength, gait speed, and 6-min walking distance, at baseline (2009-2013) and in the second phase of assessments (2013-2020)., Main Outcome Measures: Pulse pressure was calculated as the difference between systolic and diastolic blood pressure values. Weakness, slowness, and low endurance were defined as decreases of ≥0.23 m/s (one standard deviation) in gait speed, ≥5.08 kg in handgrip strength, and ≥ 57.73 m in a 6-min walk, as determined from baseline to the second phase of assessment. Linear and logistic regressions were employed to evaluate the associations between pulse pressure, hypertension, and decline in physical function., Results: Baseline pulse pressure was associated with future handgrip strength (beta = -0.017, p = 0.0362), gait speed (beta = -0.001, p < 0.0001), and 6-min walking distance (beta = -0.470, p < 0001). In multivariable models, only handgrip strength (beta = -0.016, p = 0.0135) and walking speed (beta = -0.001, p = 0.0042) remained significantly associated with future pulse pressure. Older adults with high systolic blood pressure (≥140 mmHg) and elevated pulse pressure (≥60 mmHg) exhibited a significantly increased risk of weakness (odds ratio: 1.30, 95 % confidence interval: 1.08-1.58), slowness (1.29, 1.04-1.59), and diminished endurance (1.25, 1.04-1.50) compared with the reference group, who exhibited systolic blood pressure of <140 mmHg and pulse pressure of <60 mmHg., Conclusions: Among older adults, pulse pressure is associated with a decline in physical function, especially in terms of strength and locomotion., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hemodynamic parameters derived from pulse wave analysis have been shown to predict long-term outcomes in patients with heart failure (HF). Here we aimed to develop a deep-learning based algorithm that incorporates pressure waveforms for the identification and risk stratification of patients with HF. The first study, with a case-control study design to address data imbalance issue, included 431 subjects with HF exhibiting typical symptoms and 1545 control participants with no history of HF (non-HF). Carotid pressure waveforms were obtained from all the participants using applanation tonometry. The HF score, representing the probability of HF, was derived from a one-dimensional deep neural network (DNN) model trained with characteristics of the normalized carotid pressure waveform. In the second study of HF patients, we constructed a Cox regression model with 83 candidate clinical variables along with the HF score to predict the risk of all-cause mortality along with rehospitalization. To identify subjects using the HF score, the sensitivity, specificity, accuracy, F1 score, and area under receiver operating characteristic curve were 0.867, 0.851, 0.874, 0.878, and 0.93, respectively, from the hold-out cross-validation of the DNN, which was better than other machine learning models, including logistic regression, support vector machine, and random forest. With a median follow-up of 5.8 years, the multivariable Cox model using the HF score and other clinical variables outperformed the other HF risk prediction models with concordance index of 0.71, in which only the HF score and five clinical variables were independent significant predictors (p < 0.05), including age, history of percutaneous coronary intervention, concentration of sodium in the emergency room, N-terminal pro-brain natriuretic peptide, and hemoglobin. Our study demonstrated the diagnostic and prognostic utility of arterial waveforms in subjects with HF using a DNN model. Pulse wave contains valuable information that can benefit the clinical care of patients with HF., (© 2024. The Author(s).)

Background: Disturbances of sleep are prevalent among children with chronic kidney disease. However, the aetiology of sleep disorders in children particularly after kidney transplantation is not clear. We sought to ascertain the prevalence and type of sleep disturbances in paediatric kidney transplant recipients and to identify predictors of sleep disturbances in this population., Methods: Caregivers of kidney transplant recipients completed online questionnaires about their child's sleep. The questionnaires utilised were the Sleep Disturbance Scale for Children (SDSC), the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), questions about sleep hygiene, and questions about restless leg syndrome. Demographic and clinical details were collected from medical records., Results: Thirty-five children were included in the study, with a median (IQR) age of 14.1 years (9.5-16.1) and median years (IQR) since transplant of 3.7 (0.7-8.7) years, and 72.0% were identified to have at least one category of sleep disturbance according to scores on the SDSC. The most common sleep disturbances reported were disorders of initiating and maintaining sleep (DIMS) (40.0%) and disorders of excessive somnolence (DOES) (31.4%). Statistically significant predictors of sleep disturbances include low estimated glomerular filtration rate and increased age. Among children who screened positive for DIMS and DOES, the majority indicated use of electronic devices in 1 h before bed., Conclusions: A high prevalence of sleep disturbances has been identified in children after kidney transplants, and some risk factors may be modifiable. Further studies are required to understand whether there are other readily modifiable predictors of sleep disturbances., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension., Methods and Results: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05)., Conclusions: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

Type 2 diabetes (T2D) and hypertension are common comorbidities and, along with hyperlipidemia, serve as risk factors for cardiovascular diseases. This study aimed to evaluate the predictive value of polygenic risk scores (PRSs) on cardiometabolic traits related to T2D, hypertension, and hyperlipidemia and the incidence of these three diseases in Taiwan Biobank samples. Using publicly available, large-scale genome-wide association studies summary statistics, we constructed cross-ethnic PRSs for T2D, hypertension, body mass index, and nine quantitative traits typically used to define the three diseases. A composite PRS (cPRS) for each of the nine traits was constructed by aggregating the significant PRSs of its genetically correlated traits. The associations of each of the nine traits at baseline as well as the change of trait values during a 3- to 6-year follow-up period with its cPRS were evaluated. The predictive performances of cPRSs in predicting future incidences of T2D, hypertension, and hyperlipidemia were assessed. The cPRSs had significant associations with baseline and changes of trait values in 3-6 years and explained a higher proportion of variance for all traits than individual PRSs. Furthermore, models incorporating disease-related cPRSs, along with clinical features and relevant trait measurements achieved area under the curve values of 87.8%, 83.7%, and 75.9% for predicting future T2D, hypertension, and hyperlipidemia in 3-6 years, respectively., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Aging of the proximal aorta can lead to increased pressure and flow pulsatility in the cerebral microcirculation, which may cause cognitive impairment. This study investigated the association between aortic characteristic impedance (Zc), an indicator of regional stiffness of the proximal aorta, and suspected mild cognitive impairment (MCI), compared with carotid-femoral pulse wave velocity (CFPWV)., Methods and Results: A total of 1461 healthy community residents (46.4% men; age range, 35-96 years [mean±SD, 59.9±11.8 years]) without a history of cardiovascular events or stroke were included in the study. Zc was estimated using applanation tonometry and echocardiography. Cognitive function was assessed using the Mini-Mental State Examination. Education-adjusted cut points were used to define suspected MCI. Subjects with suspected MCI (n=493 [33.7%]) had significantly higher Zc and CFPWV than those without. In multivariable analysis, both Zc and CFPWV were inversely associated with Mini-Mental State Examination score. Zc (odds ratio per 1 SD, 1.22 [95% CI, 1.09-1.37] and CFPWV (odds ratio per 1 SD, 1.18 [95% CI, 1.01-1.38]) was also significantly associated with suspected MCI, after adjusting for age, sex, education level, mean arterial pressure, hypertension, diabetes, low-density lipoprotein cholesterol, and smoking status. In joint analysis, Zc was significantly associated with suspected MCI, but CFPWV was not. In the age subgroups of <50 years and 50 to 70 years, only Zc was significantly associated with suspected MCI., Conclusions: This study found that Zc was significantly associated with Mini-Mental State Examination score and suspected MCI, especially in younger and middle-aged adults. These findings suggest that Zc may be a useful biomarker for identifying individuals at risk for MCI.

In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, including male gender, older age, diabetes, coronary heart disease, stroke, heart failure, sepsis, and surgery. There was an extremely high mortality rate among the first unplanned dialysis patients in Taiwan. Less than 10% of these patients underwent continued dialysis during the 5-year follow-up period. This study highlighted the urgent need for interventions to improve patient outcomes., (© 2023. Springer Nature Limited.)

Cerebral Small Vessel Disease (CSVD) frequently affects the elderly, with inflammation playing a crucial role in related health complications, including dementia, stroke, and SVD. Studies, including animal experiments, indicate a strong link between inflammation and SVD progression. The Neutrophil-Lymphocyte Ratio (NLR) serves as a possible biomarker for ongoing inflammatory risks. A total of 720 adults aged 50 years or older from the community-based I-Lan Longitudinal Aging Study were included in this study. General linear regression and ordinally logistic regression analyses were performed to evaluate the association between NLR and CSVD. We further examined the presence of lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. The NLR was positively associated with WMH (adjusted r = 0.109, p = 0.003), microbleed (adjusted r = 0.102, p = 0.006), and lacune (adjusted r = 0.100, p = 0.008). After adjustments for smoking, drinking, and physical activity in the ordinal logistic regression analysis, age, gender, brachial Systolic Blood Pressure (SBP), fasting glucose, LDL-cholesterol, and Hs-CRP were compared among subjects with low tertile (T1), medium tertile (T2) and high tertile (T3) NLR. The results showed that T2 vs. T1 had an odds ratio of 1.23 (0.86-1.77); and T3 vs. T1 had an odds ratio of 1.87 (1.29-2.71) of CSVD scores in four groups (zero (reference group), one, two, and three or more). NLR could be used to assess the state of inflammation in cerebral vessels. A significant and positive correlation between NLR and CSVD was verified in this study. However, the practical clinical application of NLR in CSVD patients and prognosis prediction should be validated through more scientific attempts.

Introduction: We investigated the prevalence of undiagnosed diabetes and impaired fasting glucose (IFG) in individuals without known diabetes in Taiwan and developed a risk prediction model for identifying undiagnosed diabetes and IFG., Research Design and Methods: Using data from a large population-based Taiwan Biobank study linked with the National Health Insurance Research Database, we estimated the standardized prevalence of undiagnosed diabetes and IFG between 2012 and 2020. We used the forward continuation ratio model with the Lasso penalty, modeling undiagnosed diabetes, IFG, and healthy reference group (individuals without diabetes or IFG) as three ordinal outcomes, to identify the risk factors and construct the prediction model. Two models were created: Model 1 predicts undiagnosed diabetes, IFG&#95;110 (ie, fasting glucose between 110 mg/dL and 125 mg/dL), and the healthy reference group, while Model 2 predicts undiagnosed diabetes, IFG&#95;100 (ie, fasting glucose between 100 mg/dL and 125 mg/dL), and the healthy reference group., Results: The standardized prevalence of undiagnosed diabetes for 2012-2014, 2015-2016, 2017-2018, and 2019-2020 was 1.11%, 0.99%, 1.16%, and 0.99%, respectively. For these periods, the standardized prevalence of IFG&#95;110 and IFG&#95;100 was 4.49%, 3.73%, 4.30%, and 4.66% and 21.0%, 18.26%, 20.16%, and 21.08%, respectively. Significant risk prediction factors were age, body mass index, waist to hip ratio, education level, personal monthly income, betel nut chewing, self-reported hypertension, and family history of diabetes. The area under the curve (AUC) for predicting undiagnosed diabetes in Models 1 and 2 was 80.39% and 77.87%, respectively. The AUC for predicting undiagnosed diabetes or IFG in Models 1 and 2 was 78.25% and 74.39%, respectively., Conclusions: Our results showed the changes in the prevalence of undiagnosed diabetes and IFG. The identified risk factors and the prediction models could be helpful in identifying individuals with undiagnosed diabetes or individuals with a high risk of developing diabetes in Taiwan., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The present study investigated the prognostic values for office brachial (OB), office central (OC), and ambulatory daytime brachial (AmDB) hypertension, as defined by a unifying threshold of 130/80 mmHg, and the incremental value of either OC or AmDB hypertension to OB hypertension. A total of 1219 community residents without receiving anti-hypertensive treatment (671 men and 548 women, aged ≥ 30 years old) from central Taiwan and Kinmen islands had OB, OC, and AmDB blood pressure measurements during a cardiovascular survey conducted in 1992-1993. OB hypertension, OC hypertension, and AmDB hypertension were all defined in retrospect at the threshold of 130/80 mmHg. They were followed up for nonfatal and fatal cardiovascular events until December 31, 2017, by linking the baseline database to the National Health Insurance Research dataset and the National Death Registry. During a follow-up of 25 612.5 person-years (Average event-free time: 21.0 years), there were 368 fatal and nonfatal cardiovascular events. In multivariable analyses, OB hypertension, OC hypertension, and AmDB hypertension had similar hazard ratios for cardiovascular events [2.03, 95% confidence interval: 1.47-2.80]; 1.92 (1.47-2.51); and 1.79 (1.41-2.29), respectively. Using OB normotension as the reference, either the concordant OB and OC hypertension [2.24 (1.61-3.12)], or the concordant OB and AmDB hypertension [2.52 (1.80-3.54)] was significantly associated with cardiovascular events. Moreover, OB hypertension plus AmDB normotension was also significantly associated with increased risk for cardiovascular events. We concluded that OB hypertension, OC hypertension, and AmDB hypertension defined by a unifying threshold of 130/80 mmHg may provide similar estimates of long-term risk for cardiovascular events. Cross-classification analyses suggest that addition of OC hypertension or AmDB hypertension may improve the prognostic value of OB hypertension., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background and Aims: Physical and cognitive function decline indicates the prestage of disability and is associated with mortality among older adults. We investigated the association of metabolic disorders in midlife with physical and cognitive function decline in later life in a retrospective cohort., Material and Methods: A total of 618 older adults aged ≥60 years in wave-6 (2014-2017) were enrolled in the Cardiovascular Disease Risk Factor Two-Township Study to evaluate physical (hand grip strength and 4-m walking speed) and cognitive function (Mine-Mental State Examination [MMSE] score). Repeated metabolic disorder measures in wave-2, wave-3, and wave-5 were obtained to identify three trajectory pattern groups according to each metabolic disorder through group-based trajectory modeling. Linear and logistic regressions were conducted to investigate the association of metabolic disorders in middle life with physical and cognitive function decline in later life., Results: The prevalence rates of a weak hand grip (<28 kg for men and <18 kg for women), slow walking speed (<0.8 m/s), and poor cognitive function (MMSE <25) were 24.43 %, 16.83 % and 10.5 %, respectively, among the older adults. In the retrospective cohort with 15-year follow-up, those with a waist circumference of ≥95 cm for men and ≥85 cm for women in middle life exhibited a significantly weak hand grip (odds ratio: 2.78 [95 % confidence interval: 1.26, 6.11]) and slow walking speed (2.26 [1.15, 4.43]) in later life compared with those with a smaller waist circumference (<85 cm for men and <75 cm for women). Elevated blood pressure (systolic blood pressure [BP] ≥130 mmHg or diastolic BP ≥80 mmHg) was significantly associated with a higher risk of cognitive function decline in later life. Furthermore, the high-trajectory and middle-trajectory groups' body mass index (3.17 [1.25, 8.04] and 2.27 [1.28, 4.00], respectively) and waist circumference (4.39 [2.07, 9.31] and 2.54 [1.39, 4.67], respectively) were significantly associated with a weak hand grip and slow walking speed, respectively, compared with those of the low-trajectory group. The high-trajectory diastolic BP group was significantly associated with a higher risk of cognitive function decline compared with the low-trajectory diastolic BP group., Conclusion: Waist circumference and BP in middle life were associated with physical function decline and poor cognitive function in later life. The management of central obesity and BP in midlife may slow the decline of physical and cognitive function in later life., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study is aimed at estimating the unbiased effectiveness of population-based breast cancer service screening based on case survival information alone rather than large-scale individual screening data pursuant to the intention-to-treat principle of a randomized-controlled trial., Methods: A novel time-dependent switched design with two modalities of cancer detection (screen-detected vs clinically detected) was proposed to evaluate the effectiveness of breast cancer screening. We used data on 767 patients from Kopparberg in the Swedish Two-County trial and on 78 587 patients in the Taiwan population-based service screening. We estimated the relative rate of the screen-detected vs the clinically detected with adjustment for both truncation and lead-time biases. The absolute effectiveness in terms of the number needed to screen (NNS) for averting one death from breast cancer was estimated., Results: The relative rate of effectiveness was estimated as 33%, which was consistent with the 37% reported from the original Swedish randomized-controlled trial. The corresponding estimate for the Taiwan screening programme was 42%, which was also very close to that estimated using individual screening history data (41%). Both relative estimates were further applied to yield 446 and 806 of NNS for averting one death from breast cancer for the corresponding two data sets., Conclusion: The proposed time-dependent switched design and analysis with two modalities of case survival information provides a very efficient means for estimating the unbiased estimates of relative and absolute effectiveness of population-based breast cancer service screening dispensing with a large amount of individual screening history data., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Peripheral arterial disease (PAD) is more common in patients receiving maintenance hemodialysis than in the general population. Critical limb ischemia (CLI), the most severe form of PAD, is associated with high amputation and mortality risk. However, few prospective studies are available evaluating this disease's presentation, risk factors and outcomes for patients receiving hemodialysis., Methods: The Hsinchu VA study, a prospective multicentre study, investigated the impact of clinical factors on cardiovascular outcomes of patients receiving maintenance hemodialysis from January 2008 until December 2021. We evaluated the presentations and outcomes of patients with newly diagnosed PAD and the correlations of clinical variables with newly diagnosed CLI., Results: Of 1136 study participants, 1038 had no PAD on enrolment. After a median follow-up period of 3.3 years, 128 had newly diagnosed PAD. Of these, 65 presented with CLI, and 25 underwent amputation or died from PAD. Patients presenting with CLI had more below-the-knee (52%) and multi-level (41%) disease, and completely occluded segments (41%), and higher risk for amputation or PAD-related death compared with patients without CLI (27.7% vs 9.5%, P  = .01). After multivariate adjustment, disability, diabetes mellitus, current smoking and atrial fibrillation were significantly associated with newly diagnosed CLI., Conclusions: Patients undergoing hemodialysis had higher rates of newly diagnosed CLI than the general population. Those with disabilities, diabetes mellitus, smoking and atrial fibrillation may require careful examination for PAD. Trial registration: Hsinchu VA study, ClinicalTrials.gov identifier: NCT04692636., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Guidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference-Individual Participant Data Collaboration., Methods: One-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared., Results: We analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P< 0.001). Higher arm BP models fitted better for all-cause mortality, cardiovascular mortality, and cardiovascular events (all P <0.001). Higher arm BP models better predicted cardiovascular events with Framingham and atherosclerotic cardiovascular disease risk scores (both P <0.001) and reclassified 4.6% and 3.5% of participants respectively to higher risk categories compared with lower arm BPs)., Conclusions: Using BP from higher instead of lower reading arms reclassified 12% of people over thresholds used to diagnose hypertension. All prediction models performed better when using the higher arm BP. Both arms should be measured for accurate diagnosis and management of hypertension., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: CRD42015031227.

Background: Lower cardiac index (CI) in elders has been associated with incident dementia, and higher CI has protectively effect with brain aging. In the present study, we investigated the modulating effects of education level and arterial stiffness on the association between CI and cognitive function among older adults., Methods: A total of 723 elders (≥60 years, 50.1% women) with normal left ventricular ejection fraction (≥50%) were identified from the Cardiovascular Diseases Risk Factor Two-Township Study. CI was calculated from the Doppler-derived stroke volume. We evaluated arterial stiffness by measuring carotid-femoral pulse wave velocity (CFPWV) and global cognitive function by using the Mini-Mental Short Examination (MMSE). Education level was determined by years of formal education., Results: In linear regression analysis adjusting for age, sex, formal years of education, and CFPWV, CI was significantly positively associated with MMSE (BETA=0.344±0.130, P = 0.0082). In logistic regression analysis adjusting for age, sex, formal years of education, and CFPWV, subjects with a CI≥75 percentile had a significantly lower risk of low MMSE (<26) (OR = 0.495, 95% CI = 0.274-0.896, P = 0.02). In subgroup analysis, higher CI was significantly associated with higher MMSE and lower risk of low MMSE only in elders with ≤ 9 years of formal education. Causal mediation analysis suggests that higher CI maintains higher MMSE in elders with lower education levels whereas higher CFPWV causes lower MMSE in all the elders., Conclusion: In elders with normal ejection fraction, a higher CI was associated with a lower risk of cognitive function impairment, independent of arterial stiffness, mainly in subjects with a lower education level and possibly a smaller cognitive reserve., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cheng, Chuang, Ko, Liao, Pan, Liu, Hung and Chen.)

Rationale & Objective: Frailty, a multidimensional construct, has been associated with poor outcomes in patients receiving maintenance dialysis. This study assessed the association of frailty with dialysis vascular access patency., Study Design: Multicenter prospective cohort study., Setting & Participants: 761 prevalent patients receiving hemodialysis at 9 centers in Taiwan as of January 2018., Exposure: Performance-based frailty was defined as 3 of the following: unintentional weight loss, weakness, exhaustion, low physical activity, and slow gait speed. Patients were categorized as prefrail if they had 1 or 2 of these characteristics., Outcome: Rate of and time to dialysis access thrombosis. Data regarding vascular access events were collected for 30 months after enrollment through December 31, 2020., Analytical Approach: Logistic regression analysis was used to estimate the association of clinical characteristics with frailty. Cox proportional hazards regression analysis was used to estimate the association of frailty with vascular access thrombosis adjusted for known clinical risk factors., Results: The patients' mean age was 66 years, 46% were female, 18% had synthetic graft accesses, and 82% arteriovenous fistulas. Overall, 31% were frail, 35% were prefrail, and 34% were not frail. The frailty phenotype was associated with age, female sex, low body mass index, diabetes mellitus, and prior stroke. During a median follow-up of 731 days, 161 patients (21%) had access thrombosis events (not frail, 14%; prefrail, 20%; frail, 30%; P < 0.001). Frail patients had a higher risk of vascular access thrombosis than nonfrail patients (HR, 2.31 [95% CI, 1.55-3.39], P < 0.001). After multivariable adjustment for age and comorbidities, frailty remained significantly associated with access thrombosis for both fistulas and grafts., Limitations: Limited generalizability and potential residual confounding., Conclusions: Frailty is associated with an increased risk of vascular access thrombosis. These findings highlight the risks of access failure experienced by frail patients receiving hemodialysis., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Blood pressure variability (BPV) is an important risk factor for cardiovascular events in hemodialysis patients. We sought to determine the impact of BPV on hemodialysis access thrombosis., Methods: We enrolled 1,011 prevalent hemodialysis patients from 12 hemodialysis centers since January 2018 and followed them until December 2020. Predialysis blood pressure (BP) was assessed at 12-week intervals. The coefficient of variation derived from 36 consecutive BP measurements was used as the metric for variability. The primary outcome was incident hemodialysis access thrombosis. Linear regression models were used to assess factors associated with BPV at baseline. Kaplan-Meier curves of the time until vascular access events were drawn and log-rank tests were calculated. Cox proportional hazards models were performed to assess the association of BPV with incident vascular access events., Results: The average coefficient of variance for systolic BPV was 10.9%. BPV was associated with age, body mass index, mean BP, diabetes, coronary and peripheral artery disease, history of access dysfunction, graft access, intradialytic hypotension, and use of antihypertensive medications. There were 194 access thrombosis events and 451 access stenosis events during a median follow-up period of 30 months. After adjustment of potential confounding factors, BPV was associated with increased risk of access thrombosis [hazard ratio = 1.27, 95% confidence interval (CI), 1.18-1.44, per 1 standard deviation increase in BPV]. The patients in the highest BPV quartile had 2.45 times the risk of thrombosis (CI, 1.62-3.70). The association was independent of average BP, intradialytic hypotension, and comorbidities. Similar trends of association were found in the subgroups analyzed. Comparative analysis using a time-varying variable model and different metrics of BPV showed consistent results., Conclusion: Our findings underscored the impact of BP fluctuation on vascular access thrombosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hsieh, Cheng, Chen, Liao, Lin, Yang, Chuang and Wu.)

A risk prediction model for major cardiovascular events was developed using population survey data linked to National Health Insurance (NHI) claim data and the death registry. Another set of population survey data were used to validate the model. The model was built using the Nutrition and Health Survey in Taiwan (NAHSIT) collected from 1993-1996 and linked with 10 years of events from NHI data. Major adverse cardiovascular events (MACEs) were identified based on hospital admission or death from coronary heart disease or stroke. The Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), conducted in 2002 was used for external validation. The NAHSIT data consisted of 1658 men and 1652 women aged 35-70 years. The incidence rates for MACE per 1000 person-years were 13.77 for men and 7.76 for women. These incidence rates for the TwSHHH were 7.27 for men and 3.58 for women. The model had reasonable discrimination (C-indexes: 0.76 for men; 0.75 for women), thus can be used to predict MACE risks in the general population. NHI data can be used to identify disease statuses if the definition and algorithm are clearly defined. Precise preventive health services in Taiwan can be based on this model.

Background: Frailty has been associated with mortality and adverse cardiovascular outcomes in patients with hemodialysis (HD), however the relevance of frailty on the outcomes of HD vascular access remains unclear., Methods: We enrolled a cohort of patients with prevalent HD between August 2018 and November 2018. The presence of 5 frailty phenotypes was determined at enrollment, using the modified Fried's criteria. Data regarding vascular access events or mortality were linked to prospectively collected data up to 24 months after enrollment., Results: Of the 382 patients screened, 313 were recruited in the final analysis. The participants' mean age was 66 years, and 42.5% were female. Among all participants, 40.3% were determined to be frail and 29.4% pre-frail. The frail phenotype was associated with age, female gender, lower body mass index, unemployment, lower education level, and higher dialysis clearance. During the follow-up period (median, 24 months), 112 patients had vascular access events (non-frail, 27.4%; pre-frail, 35.9%; frail, 46.1%; p = 0.003) and 45 patients experienced thrombosis of the vascular access (non-frail, 4.2%; pre-frail, 9.8%; frail, 18.3%; p = 0.002). Cox regression analysis showed that frail patients had a 2.2-fold higher risk of experiencing vascular access events than non-frail patients [hazard ratio (HR): 2.205, 95% confidence interval (CI): 1.377-3.532, p = 0.001], but the association was not significant (HR: 1.634, 95% CI: 0.938-2.848, p = 0.082) after multivariate adjustment., Conclusions: The frail phenotype is common in Taiwanese patients who undergo maintenance HD and is associated with adverse outcomes of dialysis vascular access.

The anthraquinones derived from rhubarb are reported to have anti-inflammatory activity. The present study aimed to assess the topical application of rhubarb anthraquinone aglycones for psoriasis treatment. The antipsoriatic effect of five anthraquinones, including aloe-emodin, rhein, emodin, physcion, and chrysophanol, was compared to elucidate a structure-permeation relationship. Molecular modeling was employed to determine the physicochemical properties. Both macrophages (differentiated THP-1) and keratinocytes (HaCaT) were used to examine the anti-inflammatory activity in the cell-based study. The in vitro pig skin absorption showed that chrysophanol was the compound with the highest cutaneous accumulation. Topically applied rhein was detected to be largely delivered to the receptor compartment. The absorption of rhein was increased by 5-fold in the barrier-deficient skin as compared to intact skin. By stimulating macrophages with imiquimod (IMQ) to model the inflammation in psoriasis, it was found that the anthraquinones significantly reduced IL-6, IL-23, and TNF. The cytokine inhibition level was comparable for the five compounds. The anthraquinones suppressed cytokines by inhibiting the activation of MAPK and NF-κB signaling. The anthraquinones also downregulated IL-6, IL-8, and IL-24 in the inflammatory keratinocytes stimulated with TNF. Rhein and chrysophanol were comparable to curtail the STAT3 phosphorylation in keratinocytes induced by the conditioned medium of stimulated macrophages. The IMQ-induced psoriasiform mouse model demonstrated the improvement of scaling, erythema, and epidermal hyperplasia by topically applied rhein or chrysophanol. The epidermal acanthosis evoked by IMQ was reduced with rhein and chrysophanol by 3-fold. The histological profiles exhibit that both anthraquinone compounds diminished the number of macrophages and neutrophils in the lesional skin, skin-draining lymph node, and spleen. Rhein and chrysophanol showed multifunctional inhibition, by regulating several targets for alleviating psoriasiform inflammation., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer's disease (AD) in elderly population., Objective: We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters are associated with cognitive functions in a middle-aged, non-demented population., Methods: We recruited 490 middle-aged community-based participants (30-60 years). Transcranial color-coded sonography was used to measure cerebral vascular hemodynamics, including mean flow velocity, pulsatility index, and breath-holding index (BHI) in the middle cerebral arteries (MCAs). Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). A multivariate linear regression model was used to determine the association between the MoCA scores and each intracranial hemodynamic parameter., Results: In 369 participants (median age 52 years [IQR 47-56], 48.8% men) with robust acoustic windows, the factors related to poorer MoCA scores were older age, less education extent, and the habitats of cigarette smoking or alcohol consumption. Multivariate analyses did not show a significant association between any intracranial hemodynamic parameters in both MCAs and MoCA scores in the total study population. Left MCA BHI was found to be significantly and independently correlated with the MoCA scores only in people aged 55-60 years (n = 111, B = 0.70, 95% confidence interval, 0.13-1.26, p = 0.017), however, not in people younger than 55 years., Conclusion: Our results emphasize the role of neurovascular abnormalities in the early pathophysiology of cognitive impairment and suggest cerebral vasoreactivity as the earliest detectable cognition-associated hemodynamic parameter.

Background: In patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), choosing the most appropriate antithrombotic treatment remains a dilemma. We aimed to compare the relative efficacy and safety outcomes of antithrombotic drugs in patients with AF after undergoing PCI or ACS., Methods: Randomized controlled trials were systematically searched on PubMed, EMBASE, and the Cochrane Library. Five studies (11,532 patients) were included in the network meta-analysis. Trial sequential analysis (TSA) was performed to assess the reliability and conclusiveness of the meta-analysis comparing the dual antithrombotic therapy strategies with the triple antithrombotic therapy strategy., Results: Compared with vitamin K antagonist + dual antiplatelet therapy, novel oral anticoagulant (NOAC) + P2Y12 inhibitor was associated with a significantly better trial-defined primary safety outcome (odds ratio: 0.53; 95% CI, 0.31-0.90) and the lowest probability of thrombolysis in myocardial infarction major bleeding and intracranial hemorrhage using the cumulative ranking technique. In patients omitting aspirin, TSA demonstrated conclusive evidence with significant decreases in all safety outcomes and inconclusive evidence with a nonsignificant increase in in-stent thrombosis (risk ratio: 1.32; TSA-adjusted 95% CI, 0.54-3.24) and myocardial infarction (risk ratio: 1.19; TSA-adjusted 95% CI, 0.84-1.68)., Conclusions: In patients with AF receiving PCI or with ACS, NOAC + P2Y12 inhibitor was associated with the lowest bleeding risk but resulted in a statistically nonsignificant, numerically greater risk for stent thrombosis and myocardial infarction, suggesting that triple antithrombotic therapy should still be an option for certain patients at a high risk of stent thrombosis or myocardial infarction., Competing Interests: Conflicts of interest: Dr. Chern-En Chiang, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer-review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background Glomerular hyperfiltration (GHF) is paradoxically associated with increased cardiovascular events in healthy individuals, but the pathogenesis remains unclear. We aim to investigate whether GHF is associated with mortality and whether decreased heart rate variability (HRV) is associated with GHF. Methods and Results We retrospectively analyzed 1615 participants (aged 66.1±17.3 years, 61.9% men) without prior cardiovascular events. The glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. GHF was defined as glomerular filtration rate >the 95th percentile after stratification for age and sex, whereas normal filtration was defined as the 25th to 75th percentiles. HRV indexes, including time domain, frequency domain, and sample entropy, were measured using 24-hour ambulatory electrocardiography. Clinical outcomes were defined as all-cause mortality at 2 years. During a mean follow-up of 16.5±8.2 months, there were 117 deaths (7.2%). GHF was associated with a higher risk of death (hazard ratio and 95% CIs, 1.97 [1.15-3.37]). Reduced HRV indexes, including time domain, frequency domain, and sample entropy (odds ratio and 95% CIs, 0.79 [0.70-0.89]) were all independently associated with the presence of GHF after accounting for age, sex, mean heart rate, morbidities, and medications. In subgroup analysis, reduced HRV was more predictive of GHF in the young than the elderly. Mediation analysis revealed a significant mediation effect between HRV and GHF in addition to their respective detrimental effects on survival. Conclusions Reduced HRV was independently associated with the presence of GHF. Autonomic dysfunction may be involved in the pathogenesis of adverse outcomes of GHF in individuals without prior cardiovascular events.

While psoriasis is known as a T cell- and dendritic cell-driven skin inflammation disease, macrophages are also reported to play some roles in its development. However, the signaling pathway of activated macrophages contributing to psoriasis is not entirely understood. Thus, we aimed to explore the possible mechanisms of how macrophages initiate and sustain psoriasis. The differentiated THP1 cells, stimulated by imiquimod (IMQ), were utilized as the activated macrophage model. IMQ was also employed to produce psoriasis-like lesions in mice. A transcriptomic assay of macrophages revealed that the expressions of pro-inflammatory mediators and GDAP1L1 were largely increased after an IMQ intervention. The depletion of GDAP1L1 by short hairpin (sh)RNA could inhibit cytokine release by macrophages. GDAP1L1 modulated cytokine production by activating the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways. Besides GDAP1L1, another mitochondrial fission factor, Drp1, translocated from the cytosol to mitochondria after IMQ stimulation, followed by the mitochondrial fragmentation according to the immunofluorescence imaging. Clodronate liposomes were injected into the mice to deplete native macrophages for examining the latter's capacity on IMQ-induced inflammation. The THP1 cells, with or without GDAP1L1 silencing, were then transplanted into the mice to monitor the deposition of macrophages. We found a significant THP1 accumulation in the skin and lymph nodes. The silencing of GDAP1L1 in IMQ-treated animals reduced the psoriasiform severity score from 8 to 2. After depleting GDAP1L1, the THP1 recruitment in the lymph nodes was decreased by 3-fold. The skin histology showed that the GDAP1L1-mediated macrophage activation induced neutrophil chemotaxis and keratinocyte hyperproliferation. Thus, mitochondrial fission can be a target for fighting against psoriatic inflammation.

Background: Dietary Approaches to Stop Hypertension (DASH)-Sodium trial showed that dietary sodium and potassium affect blood pressure (BP). We aimed to investigate whether dietary sodium and potassium affect short-term BP variability (BPV) in addition to BP., Methods: A total of 343 participants from the DASH-Sodium trial (age 48.4 ± 9.7, 42.5% men) and 323 individuals from the Jackson Heart Study (JHS) (age 56.7 ± 11.2, 30.7% men) with satisfactory ambulatory BP monitoring records and 24-h urine collection were included. Average real variability (ARV) was calculated as a measure of short-term BPV., Results: By estimating dietary intake from urinary excretion, we observed that higher urinary sodium-to-potassium ratio was significantly associated with higher diastolic ARV in both studies. Among the DASH-Sodium trial, potassium-rich DASH diet alone had insignificant effect on both systolic (-0.1 ± 1.7 mmHg, P = 0.343) or diastolic ARV (-0.2 ± 1.5 mmHg, P = 0.164), whereas combined DASH diet and low sodium intake significantly reduced both systolic (8.5 ± 1.6 vs. 8.9 ± 1.7 mmHg, P = 0.032) and diastolic ARV (7.5 ± 1.5 vs. 7.8 ± 1.6 mmHg, P = 0.025) as compared with control diet and high sodium intake. As the reduction of systolic ARV was majorly derived from the change of mean SBP, diastolic ARV was significantly determined by urinary sodium-to-potassium ratio (β coefficient ± standard error: 0.012 ± 0.004; P = 0.006) after adjusting for age, sex, smoking, mean DBP, BMI, and race., Conclusion: Dietary sodium and potassium can jointly modulate short-term BPV in addition to BP. Combined DASH diet and low sodium intake may reduce systolic and diastolic ARV via different mechanisms., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There are few studies demonstrating how the effectiveness of various extents of non-pharmaceutical interventions (NPIs) before and after vaccination periods. The study aimed to demonstrate such an effectiveness in the alteration of the epidemic curves from theory to practice., Methods: The empirical data on the daily reported COVID-19 cases were extracted from open source. A computer simulation design in conjunction with the susceptible-exposed-infected-recovered (SEIR) type model was applied to evaluating confinement measures in Italy with adjustment for underreported cases; isolation and quarantine in Taiwan; and NPIs and vaccination in Israel., Results: In Italy scenario, the extents of confinement measures were 34% before the end of March and then scaled up to 70% after then. Both figures were reduced to 22-69% after adjusting for underreported cases. Approximately 44% of confinement measures were implemented in the second surge of pandemic in Italy. Fitting the observational data on Taiwan assuming the initial outbreak similar to Wuhan, China, 44% of isolation and quarantine were estimated before March 23rd, 2020. Isolation and quarantine were scaled up to 90% and at least 60% to contain community-acquired outbreaks from March 24th, 2020 onwards. Given 15% monthly vaccination rate from December 2020 in Israel, the effectiveness estimates of reducing the infected toll were 36%, 56%, and 85% for NPIs alone, vaccination alone, and both combined, respectively., Conclusion: We demonstrated how various NPIs stamp out and delay the epidemic curve of COVID-19. The optimal implementation of these NPIs has to be planned before wide vaccine uptake worldwide., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

High-glucose (HG) suppresses mesenchymal stem cell (MSC) functions, resulting in a decrease in cardiac regenerative capability for MSC in diabetes mellitus (DM). Resveratrol enhances MSC functions under stress. This study explores if cardiac regenerative capability can be enhanced in MSCs pretreated with resveratrol in DM rats receiving MSCs. In vitro evidence confirms that HG decreases MSCs capability through suppression of survival markers, AMP-activated protein kinase (AMPK)/Sirtuin 1 (Sirt1) axis, and expression of apoptotic markers. All of these markers are improved when MSCs are cocultured with resveratrol. Wistar male rats were randomly divided into Sham, DM (DM rats), DM rats with autologous transplantation of adipose-derived stem cells (DM + ADSC), and DM rats with resveratrol pretreated ADSC (DM + RSVL-ADSC). Compared to the Sham, DM induces pathological pathways (including fibrosis, hypertrophy, and apoptosis) and suppresses survival as well as the AMPK/Sirt1 axis in the DM group. DM + ADSC slightly improves the above pathways whereas DM + RSVL-ADSC significantly improves the above pathways when compared to the DM group. These results illustrate that resveratrol pretreated with MSCs may show clinical potential in the treatment of heart failure in patients with DM., (© 2020 Wiley Periodicals LLC.)

The spread of the emerging pathogen, named as SARS-CoV-2, has led to an unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light on the similarity on global transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on the inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (non-pharmaceutical interventions (NPIs) and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss, and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Antrodia cinnamomea exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. We aimed to explore the antipsoriatic potential of 2,4-dimethoxy-6-methylbenzene-1,3-diol (DMD) derived from A. cinnamomea . The macrophages activated by imiquimod (IMQ) were used as the cell model for examining the anti-inflammatory effect of DMD in vitro . A significantly high inhibition of IL-23 and IL-6 by DMD was observed in THP-1 macrophages and bone marrow-derived mouse macrophages. The conditioned medium of DMD-treated macrophages could reduce neutrophil migration and keratinocyte overproliferation. DMD could downregulate cytokine/chemokine by suppressing the phosphorylation of mitogen-activated protein kinases (MAPKs) and NF-κB. We also observed inhibition of GDAP1L1/Drp1 translocation from the cytoplasm to mitochondria by DMD intervention. Thus, mitochondrial fission could be a novel target for treating psoriatic inflammation. A psoriasiform mouse model treated by IMQ showed reduced scaling, erythema, and skin thickening after topical application of DMD. Compared to the IMQ stimulation only, the active compound decreased epidermal thickness by about 2-fold. DMD diminished the number of infiltrating macrophages and neutrophils and their related cytokine/chemokine production in the lesional skin. Immunostaining of the IMQ-treated skin demonstrated the inhibition of GDAP1LI and phosphorylated Drp1 by DMD. The present study provides insight regarding the potential use of DMD as an effective treatment modality for psoriatic inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chuang, Chen, Yang, Alalaiwe, Lin and Fang.)

Background: Few longitudinal studies have investigated the association between foods/dietary pattern and mortality risk in the Asian population. We investigated the prospective association between foods/dietary pattern and risk of death among ethnic Chinese adults in Taiwan., Methods: The study population included 2475 young and middle-aged adults (aged 18-65 years at baseline) who completed the questionnaires and physical examinations in the Nutrition and Health Survey in Taiwan from 1993 to 1996. A food frequency questionnaire was administered to assess food consumption habits in a face-to-face interview. With survey data linked to the Taiwanese Death Registry, Cox proportional hazard model was used to identify the foods associated with all-cause mortality(followed until 2012), which were then tallied to calculate a dietary pattern score called Taiwanese Eating Approach(TEA) score. The TEA scores were then associated with various kinds of mortality outcomes. In addition, data from 431 elders (aged≥65 yrs) with 288 death endpoints were used to conduct a sensitivity analysis., Results: A total of 385(15.6%) participants died (111 cardiovascular related deaths and 122 cancer related deaths) during the 17.8-year follow-up period(41274 person-years). Twelve foods (9 inverse [vegetables/fish/milk/tea](+1) and 3 positive[fatty meats/fermented vegetables/sweet drinks](-1)) were significantly associated with all-cause mortality risk. All adults were grouped by their cumulative food score into three diet groups: poor diet(29.3% of all subjects), average diet(44.0%), and healthy diet(26.70%). The better the diet, the lower the total, cardiovascular, and other cause mortality outcomes (trend-p < .001). The hazard ratio for the healthy diet was 0.64 (95% confidence interval:0.47-0.87) for total mortality, and 0.52(0.28-0.95) for cardiovascular death, compared with the poor diet in the multivariable models. This phenomenon was also seen in older adults for all-cause, cancer, and other cause mortalities., Conclusion: Consuming a healthy Taiwanese Eating Approach (TEA) diet is negatively associated with all-cause, cardiovascular, and other-cause mortalities in Taiwan., Competing Interests: The authors have declared that no competing interests exist.

Aims: Microalbuminuria is an indicator of adverse cardiovascular events and chronic kidney disease. Studies have described an elevated resting heart rate as a risk factor for microalbuminuria in people with cardiovascular disease, but none have clarified its role in microalbuminuria development in people with type 2 diabetes. Therefore, this study investigated the relationship between resting heart rate and new-onset microalbuminuria in type 2 diabetes., Methods: A total of 788 people from a glycaemic control trial in Taiwan were enrolled. Microalbuminuria was defined as a fasting urine albumin-to-creatinine ratio ≥30 mg/g in two consecutive urine tests. Resting heart rate and other covariates were measured at baseline. The quartile of resting heart rates, categorized as <70, 70-74, 75-80 and >80 beats/min, was used for analysis. Cox proportional hazard models were used to evaluate the association between resting heart rate and risk of microalbuminuria., Results: During the follow-up period, 244 people (31%) developed microalbuminuria. Those who developed microalbuminuria had a longer diabetes duration (median = 3.0 vs. 2.0 years, p < 0.001), higher rate of hypertension (77% vs. 66%, p = 0.003), higher rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment (50% vs. 38%, p = 0.001) and higher baseline HbA 1c level (70 vs. 64 mmol/mol, 8.6 vs. 8.0%, p < 0.001). After adjusting for demographics, metabolic profiles and inflammatory markers, developing microalbuminuria was significantly associated with baseline resting heart rate of 70-74, 75-80 and >80 beats/min (with hazard ratios [95% CI] of 2.05 [1.32, 3.18], 2.10 [1.32, 3.32] and 1.62 [1.01, 2.59], respectively) compared to resting heart rates <70 beats/min. An average increased risk of microalbuminuria for increment of 10 beats/min was about 24% among those with hypertension (with hazard ratios of 1.24 [1.05, 1.47] in the multivariable Cox model)., Conclusions: This prospective cohort study showed that resting heart rate may be an associative risk factor for developing microalbuminuria in type 2 diabetes., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Cerebral small vessel disease (CSVD) is a common finding on brain magnetic resonance imaging (MRI). We previously demonstrated that high blood pressure (BP) and low carotid flow velocity were associated with cerebrovascular disease. However, their associations with brain volume and CSVD remain to be determined. A total of 721 adults (≥ 50 years) from the community-based I-Lan Longitudinal Aging Study were included. Flow velocities at the common (CCA) and internal carotid artery (ICA), including peak systolic velocity (PSV) and end-diastolic velocity (EDV), were measured with Doppler ultrasound. We further detected the presence of CSVD including lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. General linear regression and logistic regression analysis were exploited to evaluate the association between carotid flow velocity, BP, brain volume, and CSVD. The mean of white matter, gray matter, and WMH volume were 422.2 cm 3 , 546.9 cm 3 , and 2.61 cm 3 , respectively. The proportion of lacune and microbleed were 11.1% and 14.2%, respectively. The CSVD score were negatively associated with gray (r = - 0.121, p < .01) and white matter volume (r = 0.058, p = 0.12), but positively associated with systolic BP (beta = 1.02, p = 0.0017). EDV at common carotid artery associated positively with white matter volume (beta = 1.013, p = 0.0064) and negatively predicted the presence CSVD (odds ratio [OR] = 0.93, p = 0.0023). In the ordinal logistic regression analysis adjusting for age, sex, total intracranial volume education, low-density lipoprotein cholesterol, and fasting glucose, compared with hypertensive subjects with low EDV, normotensive subjects with low, middle, and high EDV had an odds ratio of 0.656 (0.327-1.318), 0.429 (0.261-0.705), and 0.272 (0.147-0.502) for CSVD score, respectively. High SBP and low carotid flow velocities were independently associated with brain volume and CSVD. These associations may be involved in the pathophysiology of cognitive function decline.