A Regulatory Circuit Controlling the Dynamics of NFκB cRel Transitions B Cells from Proliferation to Plasma Cell Differentiation.

Humoral immunity depends on efficient activation of B cells and their subsequent differentiation into antibody-secreting cells (ASCs). The transcription factor NFκB cRel is critical for B cell proliferation, but incorporating its known regulatory interactions into a mathematical model of the ASC differentiation circuit prevented ASC generation in simulations. Indeed, experimental ectopic cRel expression blocked ASC differentiation by inhibiting the transcription factor Blimp1, and in wild-type (WT) cells cRel was dynamically repressed during ASC differentiation by Blimp1 binding the Rel locus. Including this bi-stable circuit of mutual cRel-Blimp1 antagonism into a multi-scale model revealed that dynamic repression of cRel controls the switch from B cell proliferation to ASC generation phases and hence the respective cell population dynamics. Our studies provide a mechanistic explanation of how dysregulation of this bi-stable circuit might result in pathologic B cell population phenotypes and thus offer new avenues for diagnostic stratification and treatment.

Syphilis and cardiovascular risk: a Taiwanese registry.

BACKGROUND AND AIMS: Studies on the impact of syphilis on the cardiovascular system in large populations are limited. This study investigated the effects of syphilis on cardiovascular outcomes. METHODS: Medical records from 2010 to 2015 were retrieved from the Taiwan National Health Insurance Research Database, linked to the Notifiable Infectious Diseases database from the Taiwan Centers for Disease Control. Patients with syphilis were identified, excluding those with missing information, under 20 years of age, or with a history of human immunodeficiency virus infection, acute myocardial infarction, heart failure, aortic regurgitation, replacement of the aortic valve, aneurysm and/or dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, and venous thromboembolism. Primary outcomes included new-onset acute myocardial infarction, heart failure, aortic regurgitation, aneurysm and dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, cardiovascular death, and all-cause mortality. RESULTS: A total of 28 796 patients with syphilis were identified from 2010 to 2015. After exclusions and frequency matching, 20 601 syphilis patients and 20 601 non-syphilis patients were analysed. The relative rate (RR) was utilized in the analysis, as the competing risk of death was not considered. Compared with patients without syphilis, patients with syphilis had increased risks of acute myocardial infarction (RR 38%, 95% confidence interval [CI] 1.19-1.60, P < .001), heart failure (RR 88%, 95% CI 1.64-2.14, P < .001), aortic regurgitation (RR 81%, 95% CI 1.18-2.75, P = .006), atrial fibrillation (RR 45%, 95% CI 1.20-1.76, P < .001), ischaemic stroke (RR 68%, 95% CI 1.52-1.87, P < .001), haemorrhagic stroke (RR 114%, 95% CI 1.74-2.64, P < .001), venous thromboembolism (RR 67%, 95% CI 1.23-2.26, P = .001), cardiovascular death (RR 155%, 95% CI 2.11-3.08, P < .001), and all-cause death (RR 196%, 95% CI 2.74-3.19, P < .001) but not for aneurysm and dissection of the aorta. CONCLUSIONS: This study demonstrates that patients with syphilis have a higher risk of cardiovascular events and all-cause mortality compared with those without syphilis.

Leadless pacemaker implementation at the right atrial appendage apex: An initial preclinical assessment.

OBJECTIVE: This study evaluates the feasibility and efficacy of implanting a leadless pacemaker at the right atrial appendage (RAA) in a preclinical minipig model, aiming to address the limitations of atrial pacing with current leadless devices like the Medtronic Micra, which is typically used for right ventricular implantation. METHODS: Four minipigs, each with a median body weight of 45.8 ± 10.0 kg, underwent placement of the Micra transcatheter pacing system (TPS) via the right femoral vein into the RAA apex. The pacing performance was assessed over 1-week (short-term) and 3-month (long-term) periods. OUTCOMES: The initial findings indicated successful implantation, with satisfactory intrinsic R-wave amplitudes and pacing threshold. In the following period, the sensitivity, threshold, and impedance were stable with time. Notably, upon explanation at 3 months, a deep myocardial penetration by the device was observed, necessitating a redesign for safe long-term use in a growing subject's heart. CONCLUSION: While initial results suggest that RAA apex placement of the Micra TPS is promising for potential inclusion in a dual-chamber pacing system, the issue of myocardial penetration highlights the need for device redesign to ensure safety and effectiveness in long-term applications.

Cardiovascular and renal outcomes in patients with atrial fibrillation and stage 4-5 chronic kidney disease receiving direct oral anticoagulants: a multicenter retrospective cohort study.

The role of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and stage 4-5 chronic kidney disease (CKD) is controversial. Electronic medical records from 2012 to 2021 were retrieved for patients with AF and stage 4-5 CKD receiving oral anticoagulants. Patients were separated into those receiving DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) or vitamin K antagonists (VKA). Primary outcomes included ischemic stroke (IS), systemic thrombosis (SE), major bleeding, gastrointestinal bleeding, hemorrhagic stroke, acute myocardial infarction, cardiovascular death, and all-cause death. Renal outcomes included eGFR declines, creatinine doubling, progression to dialysis, and major adverse kidney events (MAKE). The primary analysis was until the end of follow up and the results at 1-year and 2-year of follow ups were also assessed. 2,382 patients (DOAC = 1,047, VKA = 1,335) between 2012 and 2021 with AF and stage 4-5 CKD were identified. The mean follow-up period was 2.3 ± 2.1 years in DOCAs and 2.6 ± 2.3 years in VKA respectively. At the end of follow up, the DOAC patients had significantly decreased SE (subdistribution hazard ratio [SHR] = 0.50, 95% confidence interval [CI] = 0.34-0.73), composite of IS/SE (SHR = 0.78, 95% CI = 0.62-0.98), major bleeding (HR = 0.77, 95% CI = 0.66-0.90), hemorrhagic stroke (HR = 0.52, 95% CI = 0.36-0.76), and composite of bleeding events (SHR = 0.80, 95% CI = 0.69-0.92) compared with VKA patients. The IS efficacy outcome revealed neutral between DOAC and VKA patients (HR = 1.05, 95% CI = 0.79-1.39). In addition, DOAC patients had significantly decreased rates of eGFR decline > 50% (SHR = 0.75, 95% CI = 0.64-0.87), creatinine doubling (SHR = 0.80, 95% CI = 0.67-0.95), and MAKE (SHR = 0.81, 95% CI = 0.71-0.93). In patients with AF and stage 4-5 CKD, use of DOAC was associated with decreased rates of a composite of ischemic stroke/systemic embolism, a composite of bleeding events, and renal events compared to VKA. Efficacy and safety benefits associated with apixaban at standard doses were consistent throughout follow-up.

Label-free and noninvasive analysis of microorganism surface epistructures at the single-cell level.

Cell surface properties of microorganisms provide abundant information for their physiological status and fate choice. However, current methods for analyzing cell surface properties require labeling or fixation, which can alter the cell activity. This study establishes a label-free, rapid, noninvasive, and quantitative analysis of cell surface properties, including the presence and the dimension of epistructure, down to the single-cell level and at the nanometer scale. Simultaneously, electrorotation provides dielectric properties of intracellular contents. With the combined information, the growth phase of microalgae cells can be identified. The measurement is based on electrorotation of single cells, and an electrorotation model accounting for the surface properties is developed to properly interpret experimental data. The epistructure length measured by electrorotation is validated by scanning electron microscopy. The measurement accuracy is satisfactory in particular in the case of microscale epistructures in the exponential phase and nanoscale epistructures in the stationary phase. However, the measurement accuracy for nanoscale epistructures on cells in the exponential phase is offset by the effect of a thick double layer. Lastly, a diversity in epistructure length distinguishes exponential phase from stationary phase.

Photon color conversion enhancement of colloidal quantum dots inserted into a subsurface laterally-extended GaN nano-porous structure in an InGaN/GaN quantum-well template.

To improve the color conversion performance, we study the nanoscale-cavity effects on the emission efficiency of a colloidal quantum dot (QD) and the Förster resonance energy transfer (FRET) from quantum well (QW) into QD in a GaN porous structure (PS). For this study, we insert green-emitting QD (GQD) and red-emitting QD (RQD) into the fabricated PSs in a GaN template and a blue-emitting QW template, and investigate the behaviors of the photoluminescence (PL) decay times and the intensity ratios of blue, green, and red lights. In the PS samples fabricated on the GaN template, we observe the efficiency enhancements of QD emission and the FRET from GQD into RQD, when compared with the samples of surface QDs, which is attributed to the nanoscale-cavity effect. In the PS samples fabricated on the QW template, the FRET from QW into QD is also enhanced. The enhanced FRET and QD emission efficiencies in a PS result in an improved color conversion performance. Because of the anisotropic PS in the sample surface plane, the polarization dependencies of QD emission and FRET are observed.

Surface plasmon coupling effects on the photon color conversion behaviors of colloidal quantum dots in a GaN nanoscale hole with a nearby quantum-well structure.

To improve color conversion performance for color display application, we study the near-field-induced nanoscale-cavity effects on the emission efficiency and Förster resonance energy transfer (FRET) under the condition of surface plasmon (SP) coupling by inserting colloidal quantum dots (QDs) and synthesized Ag nanoparticles (NPs) into surface nano-holes fabricated on a GaN template and an InGaN/GaN quantum-well (QW) template. In the QW template, the inserted Ag NPs are close to either QWs or QDs for producing three-body SP coupling to enhance color conversion. Time-resolved and continuous-wave photoluminescence (PL) behaviors of the QW- and QD-emitting lights are investigated. The comparison between the nano-hole samples and the reference samples of surface QD/Ag NP shows that the nanoscale-cavity effect of the nano-hole leads to the enhancements of QD emission, FRET between QDs, and FRET from QW into QD. The SP coupling induced by the inserted Ag NPs can enhance the QD emission and FRET from QW into QD. Its result is further enhanced through the nanoscale-cavity effect. The relative continuous-wave PL intensities among different color components also show the similar behaviors. By introducing SP coupling to a color conversion device with the FRET process in a nanoscale cavity structure, we can significantly improve the color conversion efficiency. Simulation results confirm the basic observations in experiment.

Sacubitril/valsartan improves all-cause mortality in heart failure patients with reduced ejection fraction and chronic kidney disease.

BACKGROUND: Impaired renal function is frequently observed in patients with heart failure and reduced ejection fraction (HFrEF). The differential effect of sacubitril/valsartan and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEIs/ARBs) on the clinical and renal outcomes in patients with HFrEF and chronic kidney disease (CKD) remains unknown. AIMS: This study aimed to explore the differential effect of sacubitril/valsartan and ACEI/ARB on the clinical and renal outcomes as well as renal function over a 12-month follow-up period in HFrEF patients with and without CKD. METHODS: Patients with HfrEF (LVEF ≤35%) and NYHA class ≥II were enrolled from the Chang Gung Research Database between 2017 and 2020. Baseline characteristics were compared between patients prescribed sacubitril/valsartan and ACEI/ARB. After propensity score matching, the following clinical and renal outcomes were compared between the two groups in patients with and without CKD over a 12-month follow-up period: acute kidney injury (AKI), emergent dialysis/renal death, HF hospitalization, cardiovascular mortality, and all-cause mortality. RESULTS: This study enrolled 3735 HFrEF patients with a mean left ventricular EF of 27.56 ± 5.86%, who had been prescribed sacubitril/valsartan (N = 1708) or ACEI/ARB (N = 2027). After propensity score matching, the clinical and renal outcomes did not differ between the sacubitril/valsartan and ACEI/ARB groups in patients without CKD. In patients with CKD, the ACEI/ARB group had a significantly higher incidence of all-cause mortality than the sacubitril/valsartan group (14.89% vs. 10.50%; hazard ratio 1.46; 95% confidence interval 1.06-2.00; p = 0.02), and the incidence of AKI, HF hospitalization, and CV mortality did not differ between the two groups. CONCLUSIONS: Sacubitril/valsartan had a lower all-cause mortality compared to ACEI/ARB in symptomatic HFrEF patients with CKD. Further prospective randomized studies are warranted to confirm our findings.

Acute heart failure with mildly reduced ejection fraction and myocardial infarction: a multi-institutional cohort study.

BACKGROUND: Little research has been done on ischemic outcomes related to left ventricular ejection fraction (EF) in acute decompensated heart failure (ADHF). METHODS: A retrospective cohort study was conducted between 2001 and 2021 using the Chang Gung Research Database. ADHF Patients discharged from hospitals between January 1, 2005, and December 31, 2019. Cardiovascular (CV) mortality and heart failure (HF) rehospitalization are the primary outcome components, along with all-cause mortality, acute myocardial infarction (AMI) and stroke. RESULTS: A total of 12,852 ADHF patients were identified, of whom 2,222 (17.3%) had HFmrEF, the mean (SD) age was 68.5 (14.6) years, and 1,327 (59.7%) were males. In comparison with HFrEF and HFpEF patients, HFmrEF patients had a significant phenotype comorbid with diabetes, dyslipidemia, and ischemic heart disease. Patients with HFmrEF were more likely to experience renal failure, dialysis, and replacement. Both HFmrEF and HFrEF had similar rates of cardioversion and coronary interventions. There was an intermediate clinical outcome between HFpEF and HFrEF, but HFmrEF had the highest rate of AMI (HFpEF, 9.3%; HFmrEF, 13.6%; HFrEF, 9.9%). The AMI rates in HFmrEF were higher than those in HFpEF (AHR, 1.15; 95% Confidence Interval, 0.99 to 1.32) but not in HFrEF (AHR, 0.99; 95% Confidence Interval, 0.87 to 1.13). CONCLUSION: Acute decompression in patients with HFmrEF increases the risk of myocardial infarction. The relationship between HFmrEF and ischemic cardiomyopathy, as well as optimal anti-ischemic treatment, requires further research on a large scale.

Understanding the Dynamics of Unwanted Online Sexual Solicitation Among Youth in Taiwan: Vulnerability and Resilience Factors.

The rise in online sexual exposure and solicitation among youth has heightened concerns. Youth, due to their limited socio-cognitive capacity, face greater risks of online sexual victimization compared to adults. Unwanted online sexual solicitation (UOSS) is a concerning aspect of sexual victimization, encompassing requests for unwanted sexual talks, activities, and sharing personal sexual information or images online. This study, based on target congruence theory, examined UOSS risk and protective factors using a national-representative youth sample in Taiwan. In 2020, 19,556 students (Grades 5-12, average age 15, 50% male) participated in the school-based online survey. Hierarchical linear regression was used to determine the significance of UOSS predictors. Findings revealed a 15.4% prevalence of UOSS. Accounting for age and gender, target-vulnerability variables (self-esteem, bullying victimization, psychological distress) and target-gratifiability variables (online self-disclosure, time spent online) significantly linked to UOSS. Youth who were bullied, had greater psychological distress and online self-disclosure, and increased Internet use were prone to UOSS, while self-esteem mitigated risks. Bullying victimization and online self-disclosure were the strongest correlates of UOSS in Taiwan's youth, followed by psychological distress, Internet usage, and self-esteem. In sum, this study enriches the understanding of UOSS among Taiwanese youth and suggests strategies to prevent online sexual victimization. Enhancing self-esteem, promoting social media education including online privacy and self-disclose, tackling bullying, addressing psychological distress, and furnishing relevant services are crucial preventive measures. These findings offer guidance to parents, educators, and health professionals for supervising and steering adolescents' online conduct, presenting an evidence-based framework to avert online sexual victimization.

An Exergame-Integrated IoT-Based Ergometer System Delivers Personalized Training Programs for Older Adults and Enhances Physical Fitness: A Pilot Randomized Controlled Trial.

INTRODUCTION: Regular physical exercise is believed to counteract the adverse physiological consequences of aging. However, smart fitness equipment specifically designed for older adults is quite rare. Here we designed an exergame-integrated internet of things (IoT)-based ergometer system (EIoT-ergo) that delivers personalized exercise prescriptions for older adults. First, physical fitness was evaluated using the Senior Fitness Test (SFT) application. Then, radio frequency identification (RFID) triggered the EIoT-ergo to deliver the corresponding exercise session based on the individual level of physical fitness. The exercise intensity during each workout was measured to generate the next exercise session. Further, EIoT-ergo provides an exergame to help users control and maintain their optimal cadence while engaging in exercise. METHODS: This was a randomized controlled trial with 1:1 randomization. Participants were older adults, 50+ years of age (N = 35), who are active in their community. Participants in the EIoT-ergo group received a 12-week personalized exercise program delivered by EIoT-ergo for 30 min per session, with 2 sessions per week. Participants in the control group continued with their usual activities. A senior's fitness test and a health questionnaire were assessed at baseline and at a 13-week reassessment. The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) was used to evaluate the satisfaction of EIoT-ergo. RESULTS: Compared with the control group, the EIoT-ergo group showed significant improvements in muscle strength (time-by-group interaction, sit-to-stand: ß = 5.013, p < 0.001), flexibility (back stretch: ß = 4.008, p = 0.005; and sit-and-reach: ß = 4.730, p = 0.04), and aerobic endurance (2-min step: ß = 9.262, p = 0.03). The body composition was also improved in the EIoT-ergo group (body mass index: ß = -0.737, p < 0.001; and skeletal muscle index: ß = 0.268, p = 0.03). Satisfaction with EIoT-ergo was shown in QUEST, with an average score of 4.4 ± 0.32 (5 for very satisfied). The percentage maximum heart rate in each session also indicated that EIoT-ergo can gradually build up the exercise intensity of users. CONCLUSIONS: EIoT-ergo was developed to provide personal identification, exergames, intelligent exercise prescriptions, and remote monitoring, as well as to significantly enhance the physical fitness of the elderly individuals under study.

Effect of the Ligation and Reperfusion Timeframe on Maximal Ischemia-Reperfusion Injury in Diverse Rat Models.

Background: Little is known about the effect that different time sequences for coronary ligation and reperfusion have on ischemic-reperfusion (IR) injury. Objective: To investigate the relationship between the extent of IR injury and the timeframe for coronary ligation/reperfusion in three animal models. Methods: Three rat models were used: normal Sprague-Dawley rats, diabetes mellitus (DM) rats, and fat rats. The rats in each model were divided into four groups based on the coronary ligation period (L): 30, 60, 120, and 180 min, and then divided into seven sub-groups based on the reperfusion period (R): 0, 30, 60, 120, 180, 270, and 360 min. R0 was the IR injury baseline for each sub-group. The hearts were harvested and stained with Evans blue and 2,3,5-triphenyl tetrazolium chloride dye to distinguish the different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The difference between each subgroup and baseline (R0) for the necrotic area/AAR was calculated. Results: In the normal rats, the highest IR injury differences compared with the baseline group occurred at L120, with a reperfusion time of > 180 min. The highest IR injury difference compared to the baseline group occurred at L30, with a reperfusion time of > 180 min in the DM rats and at L60R270, L120R180 in the fat rats. Conclusions: IR injury, as induced by different coronary ligation and reperfusion time intervals, had diverse expression profiles in the different animal models. Optimal animal models with optimal coronary ligation/reperfusion protocols to achieve maximal IR injury will affect the results and interpretation of future studies.

Deficiency of circadian gene cryptochromes in bone marrow-derived cells protects against atherosclerosis in LDLR-/- mice.

Cryptochromes are photoreceptors that mediate the circadian entrainment by light in plants and animals. They are also involved in magnetic field sensing in some animals. Recent studies suggest that cryptochromes play an essential role in metabolism and cardiovascular disease. However, the tissue-specific function of cryptochromes in atherosclerosis is unknown. We transplanted bone marrow from wild-type (WT) and cryptochrome 1/2 knockout (Cry1/2 KO) mice into irradiated recipient low-density lipoprotein receptor knockout (LDLR-/- ) mice and induced atherosclerosis with a high cholesterol diet for 12 weeks. There was a reduction in atherosclerotic plaques and macrophage accumulation in the aorta of LDLR-/- mice that received Cry1/2 KO bone marrow compared to mice that received WT bone marrow. Bone marrow-derived macrophages (BMDMs) from Cry1/2 KO mice exhibited impaired uptake of low-density lipoprotein, and subsequently, impaired foam cell formation. Analysis of macrophage mRNA circadian oscillations revealed that the circadian rhythm of the LDLR mRNAs was lost in Cry1/2 KO BMDMs. Reinstalling the circadian oscillatory LDLR mRNAs using adenovirus into the BMDMs was able to rescue the lipid uptake and foam cell formation function. However, the noncircadian oscillatory LDLR mRNAs exhibited reduced ability to rescue the macrophage functions. These findings indicate that cryptochromes in bone marrow-derived cells are critical mediators of atherosclerosis through regulation of the LDLR mRNA circadian rhythm. Therapeutic measures targeting cryptochromes in the macrophage may have important implications for atherosclerosis.

Short- and Long-Term Outcomes of Catheter-Directed Thrombolysis versus Pulmonary Artery Embolectomy in Pulmonary Embolism: A National Population-Based Study.

OBJECTIVES: This study aimed to compare the short-term and long-term follow-up outcomes of catheter-directed thrombolysis (CDT) with those of pulmonary artery embolectomy (PAE) for patients with acute pulmonary embolism (PE) included in a nationwide cohort. BACKGROUND: Data allowing direct comparisons between CDT and PAE are lacking in the literature, and the optimal management of high-risk and intermediate-risk PE is still debated. METHODS: A retrospective cohort study was conducted with data for 2001 through 2013 collected from the Taiwan National Health Insurance Research Database (NHIRD). Patients who were first admitted for PE and treated with either CDT or PAE were included and compared. In-hospital outcomes included in-hospital death and safety (bleeding and cardiac arrhythmias) outcomes. Follow-up outcomes included all-cause mortality and recurrent PE during the 1- and 2-year follow-up periods and through the last follow-up. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to minimize possible selection bias, including indices for multimorbidity such as the Charlson's Comorbidity Index (CCI) and HAS-BLED scores. RESULTS: A total of 389 patients treated between January 1, 2001, and December 31, 2013, were identified; 169 underwent CDT and 220 underwent PAE. After IPTW, there were no significant differences in in-hospital mortality (18.2% vs 21.3%; odds ratio 1.07, 95% confidence interval [CI]: 0.70-1.62) or the incidence of safety outcomes between the CDT and PAE groups. The risks of all-cause mortality (30% vs 29.5%; hazard ratio 1.16, 95% CI: 0.89-1.53), recurrent PE (7.2% vs 8.7%; subdistribution hazard ratio [SHR] 0.68, 95% CI: 0.39-1.21) and new-onset pulmonary hypertension (SHR 0.25, 95% CI: 0.05-1.32) were also not significantly different between the CDT and PAE groups at 2 years of follow-up. Subgroup analysis indicated that PAE may be associated with a more favorable 2-year mortality in patients <65 years old, patients with CCI scores of <3, patients with HAS-BLED scores of 1 to 2, and patients without cardiogenic shock (all P for interaction <.05). CONCLUSIONS: In patients with PE who required reperfusion therapy, CDT and PAE resulted in similar in-hospital and long-term all-cause mortality rates and long-term rates of recurrent PE. Bleeding risks were also comparable in the 2 groups.

Impact of baseline renal function on the efficacy and safety of different Anticoagulants in Atrial Fibrillation Patients - A cohort study.

BACKGROUND: Vitamin K antagonists and different direct oral anticoagulants (DOACs) have different renal clearance rates. However, the impact of different stages of chronic renal impairment on the efficacy and safety of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in atrial fibrillation (AF) patients remains unclear. METHODS: This study enrolled AF patients from the Chang Gung Research Database. The study endpoints included thromboembolic events, major/fatal bleeding, gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). The risks of time to study endpoints between groups were compared using a Cox proportional hazards regression model with adjustment. RESULTS: This study enrolled 3525 patients with moderate renal impairment (30 ≤ creatinine clearance (CrCl) < 60 mL/min), 2846 patients with mild renal impairment (60 ≤ CrCl < 90 mL/min) and 1153 patients with CrCl ≥ 90 mL/min. Over the 3.3 ± 0.9 years follow-up period, the cumulative thromboembolic events rates and the cumulative event rates of major/fatal bleeding and ICH did not differ among the warfarin and different DOAC groups at different stages of chronic renal impairment. The annual incidences of thromboembolic events, major/fatal bleeding, GI bleeding, and ICH were similar among the warfarin and different DOAC groups at different stages of renal impairment. CONCLUSION: There did not appear to be major differences in bleeding or thromboembolic risk compared to warfarin in AF patients across a range of degree of renal failure when appropriate dose reductions of the DOACs are made.

Flexible and Controllable Metadevice Using Self-Assembly MEMS Actuator.

In this work, an actively tunable optical metadevice is proposed to realize multifunctional application by integrating self-assembly electrothermal actuator (ETA) and magnetic metamaterial. The released frame of ETA can control the deformed height of the metamaterial plate and then provide high robustness. By driving the external electromagnetic field, the metamaterial plate is actuated and rotated by a magnetic force to manipulate the incident electromagnetic response. The transmission intensities of the metadevice can be gradually increased to characterize "on" and "off" states. Along with the inputs of light source and magnetic field, the transmission results of the metadevice could provide the output of time-difference optical signal and then carry with digital information in the further optical logic operation. Such an actuation method provides an ideal platform for actively tunable metamaterial with a large tilt angle and displacement. MEMS-based metamaterial is a strategy to open an avenue for optical communication, 3D imaging, and optical logic switching applications.

Lipoprotein(a) is Associated with Cardiovascular Events in Low Risk Males: Results from a Health Checkup Cohort with Long-Term Follow-Up.

Objective: Elevated lipoprotein(a) level is an independent risk factor for atherosclerotic cardiovascular disease. However, the strength of this association in healthy individuals is unknown. Methods: In this retrospective cohort study, we reviewed medical records obtained from a Health Examination Program. The records, covering the period 2002-2015, were from 2,634 men at low risk, as indicated by their Framingham Risk Score and Systematic Coronary Risk Evaluation (SCORE) score, and included lipoprotein(a) data. We categorized the participants on the basis of their lipoprotein(a) level and analyzed the association of this level with cardiovascular events. Results: The study population had a mean age of 46 years. In total, 32 cardiovascular disease events - 6 strokes and 26 coronary artery events - were identified. An increase of 5 mg/dL in the lipoprotein(a) level (independent of low-density cholesterol) raised the cardiovascular disease risk by 8% over a period of 10 years (p = 0.014). Sensitivity analysis also yielded this result, even after excluding hypertension and diabetes. Conclusions: Elevated lipoprotein(a) may be a risk factor for coronary artery disease, even in male populations defined as having a low risk according to the Framingham Risk Score and SCORE.

Beneficial Effects of Fixed-Dose Combination of Amlodipine and Atorvastatin in Patients with Concomitant Hypertension and Hypercholesterolemia: A Multi-Institutional Cohort Study.

Background: Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases. Although treating these factors simultaneously is recommended by current guidelines, only short-term clinical results are available. Objectives: To examine the longer-term efficacy and safety of fixed-dose combination (FDC) versus free combination of amlodipine and atorvastatin in patients with concomitant hypertension and hypercholesterolemia. Methods: Patients with hypertension and hypercholesterolemia were stratified into three groups [FDC of amlodipine 5 mg/atorvastatin 10 mg (Fixed 5/10), FDC of amlodipine 5 mg/atorvastatin 20 mg (Fixed 5/20), and free combination of amlodipine 5 mg/atorvastatin 10 mg (Free 5/10)]. After inverse probability of treatment weighting, the composite CV outcome, liver function, BP, LDL-C and glycated hemoglobin (HbA1c) changes were compared. Results: A total of 1,788 patients were eligible for analysis, and the mean follow-up period was 1.7 year. There was no significant difference in the composite CV outcome among the three groups (Fixed 5/10 6.1%, Fixed 5/20 6.3% and Free 5/10 6.0%). The LDL-C level was significantly reduced in the Fixed 5/20 group (-35.7 mg/dL) compared to the Fixed 5/10 (-23.6 mg/dL) and Free 5/10 (-10.3 mg/dL) groups (p = 0.001 and < 0.001, respectively). The changes in HbA1c were similar among the three groups. Conclusions: FDC of amlodipine and atorvastatin, especially the regimen with a higher dosage of statins, significantly reduced the mid-term LDL-C level compared to a free combination in patients with concomitant hypertension and hypercholesterolemia. Blood sugar level was not significantly changed by this aggressive treatment strategy.

A nationwide cohort investigation on pay-for-performance and major adverse limb events in patients with diabetes.

A retrospective cohort study was conducted using claims data from Taiwan's National Health Insurance program to assess the effect of diabetic pay-for-performance (P4P) program on major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). This study included patients with T2DM who had completed or not completed a 1-year P4P program from 2002 to 2013. Propensity-score matching was used to balance the baseline characteristics between groups. The Cox proportional-hazard model and Fine and Gray subdistribution hazard model were used to examine the association between P4P and the risks of MALE, MACE, systemic thromboembolism (ST), heart failure (HF) hospitalization, and all-cause mortality. Patients who underwent the P4P program had a significantly decreased incidence of MALE (2.0% vs. 2.6%, subdistribution hazard ratio [SHR] 0.73, 95% CI 0.71-0.76). Regarding the individual components, the P4P group demonstrated lower risks for foot ulcer (1.1% vs 1.3%, SHR 0.80, 95% CI 0.77-0.84), gangrene (0.57% vs 0.93%, SHR 0.59, 95% CI 0.56-0.63), percutaneous transluminal angioplasty (0.61% vs 0.79%, SHR 0.72, 95% CI 0.68-0.77), and amputation (0.46% vs 0.75%, SHR 0.58, 95% CI 0.55-0.62). In addition, the risks of MACE, ST, HF hospitalization, and all-cause mortality were remarkably lower in the P4P group. The P4P program might significantly reduce critical events of MALE, MACE, ST, HF, and mortality in the diabetic population.

The impact on renal function after long-term use of anticoagulants in atrial fibrillation patients.

OBJECTIVE: Long-term oral anticoagulant should be considered or recommended in patients with atrial fibrillation (AF) and CHA2DS2VASc score ≥ 1 for stroke prevention. Warfarin and different direct oral anticoagulants (DOACs) are metabolized differently by the kidney. The impact on renal function after long-term use of anticoagulants in the patients with AF remains unclear. This study aimed to compare DOACs and warfarin's impact on the decline in renal function from a large cohort with AF. METHODS: This study included patients with nonvalvular AF from 2000 to 2018, mainly through the medical history (ICD code) of the Chang Gung Research Database. Baseline estimated glomerular filtration rate (eGFR), follow-up eGFR and the change in eGFR between 2-year eGFR and baseline eGFR were compared between different DOACs and warfarin after propensity score matching. The primary study endpoint was acute kidney injury (AKI). RESULTS: 3657 patients were enrolled in this study and the mean observation time was 3.3 ± 0.9 years. During the observation period, there was a significantly higher incidence of AKI during follow-up in the warfarin group than in the different DOAC groups before and after propensity score matching (before: warfarin vs. DOAC: 9.2% vs. 5.2%, p <  0.001; after: warfarin vs. DOAC: 8.9% vs. 4.4%, p <  0.001). There was no difference in the incidence of AKI between dabigatran group and anti-factor Xa inhibitor group after propensity score matching. The incidence of AKI was similar among rivaroxaban, apixaban and edoxaban groups after propensity score matching. The change in eGFR between 2-year eGFR and baseline eGFR did not differ between the warfarin and DOAC groups after propensity score matching (warfarin vs. DOAC: - 1.27 ± 20.32 vs. -1.94 ± 17.24 mL/min/1.73 m2, p = 0.461). CONCLUSIONS: During the mean observation time of 3.3 ± 0.9 years, warfarin was associated with a higher incidence of AKI compared with DOACs. The decline in renal function did not differ among warfarin and different DOAC groups.