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Background Exercise electrocardiography (ECG) is a noninvasive test aiming at producing ischemic changes. However, resting ECG cannot be adopted in diagnosing myocardial ischemia till ST-segment depressions. Therefore, this study aimed to detect myocardial energy defects in resting ECG using the Hilbert–Huang transformation (HHT) in patients with angina pectoris. Methods Electrocardiographic recordings of positive exercise ECG by performing coronary imaging test (n = 26) and negative exercise ECG (n = 47) were collected. Based on the coronary stenoses severity, patients were divided into three categories: normal, Results After analyzing the resting ECG using HHT, the RT intensity index was significantly higher in patients with positive exercise ECG (27.96%) than in those with negative exercise ECG (22.30%) (p Conclusions Patients with coronary stenoses had a higher RT index at the resting stage of exercise ECG. Resting ECG analyzed using HHT could be a method for the early detection of myocardial ischemia.

Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca(2+)([Ca(2+)](i)) and the third component of complement (C3) were increased in 4-AP-induced mice and astrocytes. Perturbations in the immune microenvironment in the brain were balanced by TRPV4 inhibition or the manipulation of [Ca(2+)](i) in astrocytes. Knocking down YAP with siRNA significantly inhibited 4-AP-induced pathological changes in astrocytes. Our study demonstrated that astrocytic TRPV4 activation promoted neuroinflammation through the TRPV4/Ca(2+)/YAP/STAT3 signaling pathway in mice with seizures. Astrocyte TRPV4 inhibition attenuated neuroinflammation, reduced neuronal injury, and improved neurobehavioral function. Targeting astrocytic TRPV4 activation may provide a promising therapeutic approach for managing epilepsy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01198-8.

Background Coronavirus disease 2019 (COVID-19) has caused an enormous loss of life worldwide. The spike protein of the severe acute respiratory syndrome coronavirus 2 is the cause of its virulence. Bamlanivimab, a recombinant monoclonal antibody, has been used alone or in combination with etesevimab to provide passive immunity and improve clinical outcomes. A systematic review and meta-analysis was conducted to investigate the therapeutic effects of bamlanivimab with or without etesevimab (BAM/ETE) treatment. Methods Our study was registered in PROSPERO (registry number CRD42021270206). We searched the following electronic databases, without language restrictions, until January 2023: PubMed, Embase, medRxiv, and the Cochrane database. A systematic review and meta-analysis was conducted based on the search results. Results Eighteen publications with a total of 28,577 patients were identified. Non-hospitalized patients given bamlanivimab with or without etesevimab had a significantly lower risk of subsequent hospitalization (18 trials, odds ratio (OR): 0.37, 95% confidence interval (CI): [0.29–0.49], I2: 69%; p < 0.01) and mortality (15 trials, OR: 0.27, 95% CI [0.17–0.43], I2: 0%; p = 0.85). Bamlanivimab monotherapy also reduced the subsequent risk of hospitalization (16 trials, OR: 0.43, 95% CI [0.34–0.54], I2: 57%; p = 0.01) and mortality (14 trials, OR: 0.28, 95% CI [0.17–0.46], I2: 0%; p = 0.9). Adverse events from these medications were uncommon and tolerable. Conclusions In this meta-analysis, we found the use of bamlanivimab with or without etesevimab contributed to a significantly-reduced risk of subsequent hospitalization and mortality in non-hospitalized COVID-19 patients. However, resistance to monoclonal antibodies was observed in COVID-19 variants, resulting in the halting of the clinical use of BAM/ETE. Clinicians’ experiences with BAM/ETE indicate the importance of genomic surveillance. BAM/ETE may be repurposed as a potential component of a cocktail regimen in treating future COVID variants.

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron–glia interaction mediated by the C3–TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3–TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-021-00750-4.

Background Despite the increasingly recognized impact of novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), on many aspects of health in adults and children, its effects on neonates born to infected mothers remain unclear. We conducted this study to investigate the outcomes of neonates born to mothers with COVID-19. Methods We searched the medical databases from inception to March 31, 2020 to perform a systematic review of outcomes in neonates born to mothers with COVID-19. Data were pooled using a random effects regression model. Primary and secondary outcomes were neonatal clinical outcomes and infectious status, respectively. Results Fourteen studies involving 105 neonates fulfilling the study criteria were identified. The rates of preterm neonates and those small for gestational age (SGA) were 25 (23.8%) and 10 (11.2%), respectively. Among 91 neonates who were tested, 8 (8.8%) were positive for nucleic acids or antibodies for SARS-CoV-2. Additionally, 28 (26.7%) of the neonates were symptomatic and two test-negative neonates died, including one stillbirth. Between test-positive and test-negative groups, the rates of SGA, preterm delivery, duration between maternal symptom onset and delivery, and perinatal complication were not significantly different; but the rate of symptomatic after birth reached significant difference (62.5% vs 20.5%, p = 0.008). Conclusions Most neonates born to infected mothers had favorable outcomes. Although direct evidences of intrauterine infection were scarce, the risk of intrauterine infection should be considered based on a positive test in 8.8% of the neonates. Symptomatic neonates born to infected mothers should receive tests for SARS-CoV-2 to initiate appropriate treatment and quarantine. Further studies are warranted to assess the outcomes of COVID-19 in neonates.

Objective Coronary artery disease (CAD) and cancer are the two leading causes of death worldwide. Evidence suggests the existence of shared mechanisms for these two diseases. We aimed to conduct a systematic review and meta-analysis to investigateassociation between CAD and incident cancer risk. Methods We searched Cochrane, PubMed, and Embase from inception until October 20, 2021, without language restrictions. Observational cohort studies were used to investigate the association between CAD and incident cancer risk. Using random-effects models, the odds ratio (OR) and 95% confidence interval (CI) were calculated. We utilized subgroup and sensitivity analyses to determine the potential sources of heterogeneity and explore the association between CAD and specific cancers. This study was conducted under a pre-established, registered protocol on PROSPERO (CRD42022302507). Results We initially examined 8,533 articles, and included 14 cohort studies in our review, 11 of which were eligible for meta-analysis. Patients with CAD had significantly higher odds of cancer risk than those without CAD (OR = 1.15, 95% CI = [1.08–1.22], I2 = 66%). Subgroup analysis revealed that the incident cancer risk was significantly higher in both sexes and patients with CAD with or without myocardial infarction. Sensitivity analysis revealed that the risk remained higher in patients with CAD even after >1 year of follow-up (OR = 1.23, 95% CI = [1.08–1.39], I2 = 76%). Regarding the specific outcome, the incident risk for colorectal and lung cancers was significantly higher (OR = 1.06, 95% CI = [1.03–1.10], I2 = 10%, and OR = 1.36, 95% CI = [1.15–1.60], I2 = 90%, respectively) and that for breast cancer was lower (OR = 0.86, 95% CI = [0.77–0.97], I2 = 57%) in patients with CAD than in those without CAD. Conclusion CAD may be associated with incident cancer risk, particularly for lung and colorectal cancers, in men and women as well as patients with or without myocardial infarction. Early detection of new-onset cancer and detailed cancer surveillance programs should be implemented in patients with CAD to reduce cancer-related morbidity and mortality.

Aims Excessive visceral adiposity (VAT) plays an essential role in metabolic derangements with those close to heart further mediates myocardial homeostasis. The disparate biological links between region‐specific VAT and cardiometabolic profiles as mediators influencing atrial kinetics remain unexplored. Methods and results Among 1326 asymptomatic individuals, region‐specific VAT including peri‐aortic root fat (PARF) and total pericardial fat (PCF) of cardiac region, together with thoracic peri‐aortic adipose tissue (TAT), was assessed using multiple‐detector computed tomography. VAT measures were related to functional left atrial (LA) metrics assessed by speckle‐tracking algorithm and clinical outcomes of atrial fibrillation (AF) and heart failure (HF). Multivariate linear regression models incorporating body fat, metabolic syndrome, and E/TDI‐e' consistently demonstrated independent associations of larger PARF/PCF with peak atrial longitudinal systolic strain (PALS) reduction, higher LA stiffness, and worsened strain rate components; instead, TAT was independently associated with cardiometabolic profiles. PARF rather than PCF or TAT conferred independent prognostic values for incident AF/HF by multivariate Cox regression (adjusted hazard ratio: 1.56, 95% confidence interval: 1.17–2.08, P = 0.002) during a median of 1790 days (interquartile range: 25th to 75th: 1440–1927 days) of follow‐up, with subjects categorized into worst PALS and largest VAT tertiles demonstrating highest events (all log‐rank P

The current treatment paradigm for atrial fibrillation (AF) prioritizes rate control over rhythm control; however, rhythm control has shown benefits over other AF strategies. This study compares the outcomes of rivaroxaban with and without concomitant antiarrhythmic drugs (AADs), using propensity score matching to correct for statistical effects of baseline discrepancies. This multi-center retrospective study included 1,477 patients with non-permanent AF who took rivaroxaban for at least one month between 2011 and 2016 and had not received catheter ablation. Concomitant AAD use was compared against clinical outcome endpoints for effectiveness, safety, and major adverse cardiac events (MACE). Associations with concomitant AAD use were evaluated using multivariate Cox proportional hazard analyses. Patients were divided into two matched groups: rivaroxaban alone (n = 739) and with concomitant AADs (n = 738). The cumulative incidences of safety (p = 0.308), effectiveness (p = 0.583), and MACE (p = 0.754) were similar between the two groups, and multivariate analysis showed no significant differences. The new thromboembolism and all-cause death rates were higher in rivaroxaban alone (2.7% vs 0.8%, p = 0.005; and 10% vs. 6.9%, p = 0.032, respectively). The heart failure readmission rate was higher in the concomitant-AAD group (8.4% vs. 13.3%, p = 0.003). The concomitant use of rivaroxaban with AADs appears to be well-tolerated, with lower rates of thromboembolism and all-cause death, but is associated with more occurrences of congestive heart failure.

Background The current method to evaluate the autonomic balance after renal denervation (RDN) relies on heart rate variability (HRV). However, parameters of HRV were not always predictive of response to RDN. Therefore, the complexity and disorder of heart rhythm, measured by entropy of entropy (EoE) and average entropy (AE), have been used to analyze autonomic dysfunction. This study evaluated the dynamic changes in autonomic status after RDN via EoE and AE analysis. Methods Five patients were prospectively enrolled in the Global SYMPLICITY Registry from 2020 to 2021. 24-h Holter and ambulatory blood pressure monitoring (ABPM) was performed at baseline and 3 months after RDN procedures. The autonomic status was analyzed using the entropy-based AE and EoE analysis and the conventional HRV-based low frequency (LF), high frequency (HF), and LF/HF. Results After RDN, the ABPM of all patients showed a significant reduction in blood pressure (BP) and heart rate. Only AE and HF values of all patients had consistent changes after RDN (p Conclusions Monitoring the AE and EoE analysis could be an alternative to interpreting autonomic status. In addition, a relative change of autonomic tone, especially an increasing parasympathetic activity, could restore autonomic balance after RDN.

The radial conjugated π-system of cycloparaphenylenes (CPPs) makes them intriguing fluorophores and unique supramolecular hosts. However, the bright photoluminescence (PL) of CPPs was limited to the blue light and the supramolecular assembly behavior of large CPPs was rarely investigated. Here we present the synthesis of tetra-benzothiadiazole-based [12]cycloparaphenylene (TB[12]CPP), which exhibits a lime to orange PL with an excellent quantum yield up to 82 % in solution. The PL quantum yield of TB[12]CPP can be further improved to 98 % in polymer matrix. Benefiting from its enlarged size, TB[12]CPP can accommodate a fullerene derivative or concave-convex complexes of fullerene and buckybowl through the combined π-π and C-H⋅⋅⋅π interactions. The latter demonstrates the first case of a ternary supramolecule of CPPs.

Recent studies have shown that Transmembrane protein 100 (TMEM100) is a gene at locus 17q32 encoding a 134-amino acid protein with two hypothetical transmembrane domainsa, and first identified as a transcript from the mouse genome. As a downstream target gene of bone morphogenetic protein (BMP)-activin receptor-like kinase 1 (ALK1) signaling, it was activated to participate in inducing arterial endothelium differentiation, maintaining vascular integrity, promoting cell apoptosis, inhibiting metastasis and proliferation of cancer cells. However, evidence for the function of TMEM100 in inflammation is still limited. In this study, we explore the role of TMEM100 in inflammatory cytokine secretion and the role of MAPK signaling pathways in tumor necrosis factor-alpha (TNF-α)-induced TMEM100 expression in LX-2 cells. We found that the expression of TMEM100 was decreased markedly in human liver fibrosis tissues, and its expression was also inhibited in LX-2 cells induced by TNF-α, suggesting that it might be associated with the development of inflammation. Therefore, we demonstrated that overexpression of TMEM100 by transfecting pEGFP-C2-TMEM100 could lead to the down-regulation of IL-1β and IL-6 secretion. Moreover, we found that expression changes of TMEM100 could be involved in inhibition or activation of MAPK signaling pathways accompanied with regulating phosphorylation levels of ERK and JNK protein in response to TNF-α. These results suggested that TMEM100 might play an important role in the secretion of inflammatory cytokines (IL-1β and IL-6) of LX-2 cells induced by TNF-α, and MAPK (ERK and JNK) signaling pathways might participate in its induction of expression.

The emerging data supports rhythm control to prevent major adverse cardiac events (MACE) in high-risk patients with atrial fibrillation (AF). Limited data demonstrated rivaroxaban 10 mg combining dronedarone seemed feasible. This study aimed at investigating clinical events in a dronedarone-treated cohort. This exploratory, retrospective chart review was conducted in nonpermanent AF patients receiving dronedarone for ≥ 3 months between 2009/1 and 2016/2. In Taiwan, dronedarone's labeled indication was strict to age ≥ 70 or 65 to 70 years with either hypertension, diabetes, prior stroke, or left atrium >50 mm. We divided all into 4 groups using antithrombotic strategies to evaluate the safety, effectiveness, and MACE endpoints. A total of 689 patients (mean CHA2DS2-VASc score 3.8 ± 1.4) were analyzed: rivaroxaban 10 mg (n = 93, 13.5%), warfarin (n = 89, 12.9%), antiplatelet (n = 331, 48.0%), and none (n = 176, 25.5%). During the follow-up period (mean 946 ± 493.8 days), the rivaroxaban group did not report any stroke or thromboembolism (ishcmeic stroke rate: antiplatelet [0.6%], none [1.1%]; hemorrahgic stroke rate: warfarin [2.2%]; thromboembolism rate: warfarin [2.2%]). There was no significant difference in safety, effectiveness, and MACE endpoints between groups. Also, >104 weeks of dronedarone use was the independent predictor for MACE after adjusting the strategy and other covariates (hazard ratio 0.14 [95% confidence interval 0.04-0.44], P = .001). Our findings warrant concomitant rivaroxaban 10 mg and dronedarone for further investigation. Regardless of antithrombotic strategies, a more extended persistence of dronedarone was associated with fewer MACE.

Centrifugal turbines have recently regained interest of the engineering community as they could serve as cost-effective alternatives in diverse energy applications. In this device, the working fluid expands in a centrifugal flowpath and entails rotation of concentric rings of airfoil-shaped blades. Yet in their current design paradigm, their meanline performance estimation and optimization have dubiously exploited axial turbine empirical correlations. To the authors knowledge, there are no theoretical nor practical foundation that could justify such practice. Hence, this paper intends to deliver an answer on this matter with application of the biased Kacker and Okapuu (KO) and Aungier (Ag) correlations on 33 pairs of similar axial and centrifugal cascades. The uncovered content is twofold. First, the Ag loss demonstrates a probability of achieving an error within ±15% of 44% whereas that of KO is lessened to 38% in axial cascades. The Ag deviation attains 15% which is thrice that of the KO under same condition. In second, the insensitivity of the Ag profile and secondary losses under drastic change of flow condition in the centrifugal cascades is proven to be practically significant. While the Ag deviation is still able to reach an accuracy of 11%. The coupling effect of the terms intervening in the correlations reveal to be weak. Thereupon, the empirical axial turbine loss correlations are unreliable in performance estimation or optimization of centrifugal turbines.

Exercise stress testing (EST) has limited power in diagnosing obstructive coronary artery disease (CAD). The heart rate variability (HRV) analysis might increase the sensitivity of CAD detection. This study aimed to evaluate the correlation between short-term HRV and myocardial ischemia during EST, including the acceleration, maximum, and recovery stages of heart rate (HR). The HRV during EST from 19 healthy (RHC) subjects and 35 patients with CAD (25 patients with insignificant CAD (iCAD), and 10 patients with significant CAD (sCAD)) were compared. As a result, all HRV indices decreased at the maximum stage and no significant differences between iCAD and sCAD were found. The low-frequency power of heart rate signal (LF) of the RHC group recovered relatively quickly from the third to the sixth minutes after maximum HR, compared with that of the sCAD group. The relative changes of most HRV indices between maximum HR and recovery stage were lower in the sCAD group than in the RHC group, especially in LF, the standard deviation of all normal to normal intervals (SDNN), and the standard deviation in the long axis direction of the Poincaré plot analysis (SD2) indices (p < 0.05). The recovery slope of LF was significantly smaller in the sCAD group than in the RHC group (p = 0.02). The result suggests that monitoring short-term HRV during EST provides helpful insight into the cardiovascular autonomic imbalance in patients with significant CAD. The relative change of autonomic tone, especially the delayed sympathetic recovery, could be an additional marker for diagnosing myocardial ischemia.

Melanoma is the most lethal form of skin cancer, which is intrinsically resistant to conventional chemotherapy. Combination therapy has been developed to overcome this challenge and show synergistic anticancer effects on melanoma. Notably, the histone deacetylase inhibitor, valproic acid (VPA), has been indicated as a potential sensitizer of chemotherapy drugs on various metastatic cancers, including advanced melanoma. In this study, we explored whether VPA could serve as an effective sensitizer of chemotherapy drug etoposide (ETO) on B16-F10 and SK-MEL-2-Luc melanoma cell lines in response to drug-induced DNA damages. Our results demonstrated that the VPA-ETO simultaneous combined treatment and ETO pretreated sequential combined treatment generated higher inhibitory effectivities than the individual treatment of each drug. We found the VPA-ETO simultaneous combined treatment contributed to the synergistic inhibitory effect by the augmented DNA double-strand breaks, accompanied by a compromised homologous recombination activity. In comparison, the ETO pretreated sequential combined treatment led to synergistic inhibitory effect via enhanced apoptosis. Surprisingly, the enhanced homologous recombination activity and G2/M phase arrest resulted in the antagonistic effect in both cells under VPA pretreated sequential combined treatment. In summary, our findings suggested that sequential order and effective dose of drug administration in VPA-ETO combination therapy could induce different cellular responses in melanoma cells. Such understanding might help potentiate the effectiveness of melanoma treatment and highlight the importance of sequential order and effective dose in combination therapy.

BACKGROUND This study aims to explore the clinical correlates of myocardial deformations using speckle-tracking algorithm and to determine the prognostic utility of such measures in asymptomatic ethnic Chinese population. METHODS Global longitudinal (GLS), circumferential strain (GCS), and torsion were analyzed using featured tissue-tracking algorithm among 4049 symptom-free ethnic Chinese population. Hypertrophy (LVH) was classified into 4 tiers: indeterminate, dilated, thick and thick/dilated, by gender-stratified partition of end-diastolic volume index (EDVi) and LV mass/EDV0.67. RESULTS LVH (7.3%) showed substantially lower GLS (-20.3 ± 1.82% vs. -18.9 ± 2.08%) yet higher torsion (2.20 ± 0.90 vs. 2.39 ± 1.01, p

Bowl inversion is a unique property of buckybowls. The polarity and assembly configuration of buckybowls are reversed after bowl inversion. So far, this unique phenomenon has been studied in solution and on surface, but not in solid state due to spatial constraint. Now a series of exo-type supramolecular assemblies of trithiasumanene and nanographene are investigated. Tuning the electron density of the nanogaphene component was found to directly affect the binding constant of the complex. Reversible bowl inversion in the solid state was then successfully achieved by subjecting the trithiasumanene-nanographene assembly with the weakest binding strength to repeated heating-cooling cycles, which was unambiguously observed by single crystal X-ray diffraction.

INTRODUCTION Cardiac implantable electronic devices (CIEDs) can measure atrial fibrillation (AF) early; however, the timing for administering antiarrhythmic drugs (AADs) to suppress AF remains unclear. This study aimed to investigate the association between baseline values and changes after AAD in terms of relative reduction of AF burden (RRAB) and maximum AF duration (RRMD). METHODS This multicenter retrospective study screened all patients with nonpermanent AF who had dual-chamber pacemakers and only enrolled those receiving a naive AAD between September 2009 and December 2014. AF burden and maximum duration were calculated using CIED at 0 and 3 to 6 months after starting rhythm control. All the enrolled patients were divided into four groups according to baseline AF burden. RRAB and RRMD were monitored using CIEDs. RESULTS Overall, 145 eligible subjects received a naive AAD for nonpermanent AF. The mean RRAB in the four groups (AF burden

In sustainable agriculture, sufficient crop yields and nutrients must be produced while maintaining environmental protection. Considering the role of phosphorus (P) fertilizer in influencing crops yield and environmental security, life cycle assessment was used to examine the environmental impacts of long-term P application on the grain yield and nutritional quality of winter wheat and summer maize. Thus, a long-term field experiment with six P application rates for winter wheat (0, 25, 50, 100, 200, and 400 kg P ha-1) and summer maize (0, 12.5, 25, 50, 100, and 200 kg P ha-1) was conducted on the North China Plain (NCP). The results showed that the cradle-to-farm gate eutrophication potential (EP), energy depletion (ED), and P depletion (PD) were significantly affected by the P application rate applied in winter wheat and summer maize production. The critical P rate required to ensure food security for wheat and maize was in line with the optimal rate for sustainable environmental development in terms of grain production and nutrient levels. On the NCP, the ED and PD of summer maize with optimized P management over 10 years were less than those of winter wheat regardless of using yield or nutrient level as the functional unit. However, the EP of the nutrient supply in winter wheat was less than that in summer maize under optimized P fertilization. The specific nutritional components that limited improvements in environment of wheat and maize production under the optimal P rate were energy (calories) and protein, respectively. In conclusion, in a multifunctional winter wheat-summer maize rotation system, optimized P fertilization (50 kg ha-1 for winter wheat and 25 kg ha-1 for summer maize) combined with the planting of high-yield wheat varieties and high-protein maize varieties showed great potential to reduce the environmental impacts of wheat and maize production.

Obesity has been conceptualized as a highly heterogeneous condition. We aim to investigate chamber-specific effects of obesity on the heart and relevant outcomes. A total of 2944 symptom-free individuals (age: 47.5 ± 10.0 years), free of known cardiovascular diseases were classified into four categories based on body mass index (BMI) (as normal-weight (NW) vs. overweight/obese (O)) and metabolic status (metabolically-healthy (MH) vs. unhealthy (MU)). Epicardial adipose thickness (EAT) using echocardiography method. Speckle-tracking based atrio-ventricular (LA/LV) deformations including global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS) were also analyzed. MUNW had higher cardiometabolic risks and more impaired diastolic and GLS/PALS than MHNW phenotype. Both MHO and MUO phenotypes exhibited worst atrial functions. Greater EAT was independently associated with worse GLS and PALS after correcting for various anthropometrics, LV mass and LA volume, respectively, with unfavorable LA effects from EAT being more pronounced in the NW phenotypes (both p interactions &lt, 0.05). During a median follow-up period of 5.3 years, BMI/EAT improved the reclassification for atrial fibrillation (AF) incidence (p for net reclassification improvement &lt, 0.05) mainly in the NW phenotypes (p interaction &lt, 0.001). Categorization of clinical obesity phenotypes based on excessive visceral adiposity likely provides increment prognostic impacts on atrial dysfunction, particularly in non-obese phenotypes.

Negative effects of high phosphorus (P) application on zinc (Zn) nutrition have been observed in many crops. This study investigated the Zn responses of three typical crops to varied P and Zn applications. A pot experiment was conducted using two mycorrhizal crops (maize and soybean) and one non-mycorrhizal crop (oilseed rape) under three levels of P, two levels of Zn, and two levels of benomyl. Results showed that P application significantly decreased shoot and root Zn concentrations, Zn uptake, and Zn acquisition efficiency (ZnAE) of the three crops irrespective of Zn rate, and that these reductions were greater for maize and soybean than for oilseed rape. Zn application alleviated the P inhibition of Zn uptake in the three crops. The arbuscular mycorrhizal fungi (AMF) colonization of maize and soybean contributed most to the negative effects of increasing P application on Zn uptake, explaining 79–89 and 64–69% of the effect, respectively. For oilseed rape, root dry weight and root Zn concentration explained 90% of the decrease in Zn uptake caused by P application. These results suggest that there is another pathway in addition to the mycorrhizal pathway regulating Zn uptake under mediation by P supply.

Rivaroxaban reduces the risk of thromboembolism in atrial fibrillation (AF) patients, who often also receive antiarrhythmic drugs (AADs) to maintain sinus rhythm. Current guidelines contraindicate concomitant use of rivaroxaban with the popular AAD dronedarone, despite little data demonstrating interactions with AADs. This study investigates the outcomes of concomitant rivaroxaban and AAD drug use in a real-world cohort.This retrospective study included 1777 non-permanent AF patients taking rivaroxaban for ≥ 1 month between 2011 and 2016 from a multicenter cohort in Taiwan, and compared concomitant AAD use against clinical outcome endpoints for safety, effectiveness, and major adverse cardiac events (MACE). Multivariate Cox proportional hazard analyses were used to evaluate the association between concomitant AAD use and outcomes.Patients were divided into rivaroxaban alone (n = 1205) and with concomitant amiodarone (n = 177), dronedarone (n = 231), or propafenone (n = 164) groups. The proportion of patients using rivaroxaban 10 mg was highest in the concomitant dronedarone group: rivaroxaban alone, 53.6%; with amiodarone, 57.6%; with dronedarone, 77.1%; and with propafenone, 46.3% (p 0.001). The cumulative incidences of safety (p = 0.892), effectiveness (p = 0.336), and MACE (p = 0.674) were similar between the four groups; however, there were significantly fewer new systemic thromboembolisms in the dronedarone group: rivaroxaban alone, 2.5%; with amiodarone, 0.6%; with dronedarone, 0%; and with propafenone, 1.2% (p = 0.029). The all-cause death rate was also lowest in the dronedarone group: rivaroxaban alone, 9.0%; with amiodarone, 9.6%; with dronedarone, 3.0%; and with propafenone: 6.1% (p = 0.013). After covariate adjustment, there were no differences in the safety, effectiveness, and MACE endpoints between patients receiving or not receiving AADs.Concomitant use of rivaroxaban with AADs appears to be well tolerated, warranting further investigation into the apparent benefits of a reduced dose of rivaroxaban combined with dronedarone.

Copper (Cu) and iron (Fe) are essential micronutrients for plants and animals. How phosphorus (P) application affects Cu and Fe concentrations in maize grain still remains unclear. Two-year field studies were conducted in a long-term experiment with six P levels (0, 12.5, 25, 50, 100, and 200 kg∙ha&minus, 1 P) on calcareous soil. Phosphorus application significantly decreased the average grain Cu concentration by 12.6% compared to no P treatment, but had no effect on grain Fe concentration. The copper content increased as the P application rate increased from 0 to 25 or 50 kg&middot, ha&minus, 1, but then decreased, while Fe content kept increasing. As the P application rate increased, the specific Cu uptake by the roots decreased, but not for Fe. The root length density in response to P application had a positive relationship with shoot Cu and Fe content. The shoot Cu content and grain Cu concentration decreased with the reduction in the arbuscular mycorrhizal fungi (AMF) colonization of roots due to increasing P application. The reduction in grain Cu concentration with increasing P rates could be partly explained by the decreasing uptake efficiency.

Background Low-dose rivaroxaban (10mg/day) has been commonly used in Asia for patients with atrial fibrillation (AF). However, its effectiveness and safety, particularly in patients with chronic kidney disease (CKD), is limited. Moreover, inappropriate low-dose rivaroxaban is frequently prescribed. We aimed to evaluate the effectiveness and safety of low-dose rivaroxaban in patients with or without CKD, compared to that of the standard dose in real-world practice. Methods 3122 patients with AF treated with rivaroxaban between October 2012 and December 2016 were included in this retrospective multicenter study. We compared the different doses of rivaroxaban stratified according to renal function in this cohort. Bleeding events and major adverse cardiovascular events (MACE) including CV death, MI, stroke, and thromboembolism were recorded. Results 1218 (39%) patients received standard-dose rivaroxaban (20mg/day). 1147 (36.7%) patients with eGFR>50 mL/min/1.73m2 and 757 (24.3%) patients with eGFR Conclusions The use of inappropriate low-dose rivaroxaban in patients without CKD increased MACE significantly, compared to low-dose rivaroxaban in CKD patients. In addition, the risk of bleeding was strongly associated with CKD, not with the dose of rivaroxaban. Cumulative Event Rates Funding Acknowledgement Type of funding source: None

Renal denervation (RDN) is effective to lower systolic blood pressure (SBP) in essential hypertension. However, patient selection under medications remains an important unmet clinical need.This multicenter study aimed at observing whether preprocedural features associated with increased renin-angiotensin-aldosterone activity influence RDN response. This study enrolled the patients who underwent RDN for uncontrolled hypertension. Medical records were reviewd and patients were divided into 2 groups depending by meeting any of the following conditions prior to RDN: (1)10 mmHg of office SBP reduction after aldosterone inhibition, (2) aldosterone-renin ratio30 or (3) slow flow on the renal angiogram. RDN responders were defined by a reduction in 24-hour mean ≥6 mmHg or by ≥1 class of antihypertensive drug withdraw.A total of 46 patients were enrolled, of which 27 (59%) were in control group A and 19 (41%) in group B. The baseline age, gender, office and 24-hour SBP (mean 140.0 ± 12.8 mmHg vs. 144.0 ± 16.5 mmHg,RDN was more effective in patients with any of 3 clinical indices.

Background: The aortic root diameter (AoD) has been shown to be a marker of cardiovascular risk and heart failure (HF). Data regarding the normal reference ranges in Asians and their correlates with diastolic dysfunction using contemporary guidelines remain largely unexplored. Methods: Among 5343 consecutive population-based asymptomatic Asians with echocardiography evaluations for aortic root diameter (without/with indexing, presented as AoD/AoDi) were related to cardiac structure/function and N-terminal pro-brain B-type natriuretic peptide (Nt-ProBNP), with 245 participants compared with multidetector computed tomography (MDCT)-based aortic root geometry. Results: Advanced age, hypertension, higher diastolic blood pressure, and lower body fat all contributed to greater AoD/AoDi. The highest correlation between echo-based aortic diameter and the MDCT-derived measures was found at the level of the aortic sinuses of Valsalva (r = 0.80, p < 0.001). Age- and sex-stratified normative ranges of AoD/AoDi were provided in 3646 healthy participants. Multivariate linear regressions showed that AoDi was associated with a higher NT-proBNP, more unfavorable left ventricular (LV) remodeling, worsened LV systolic annular velocity (TDI-s′), a higher probability of presenting with LV hypertrophy, and abnormal LV diastolic indices except tricuspid regurgitation velocity by contemporary diastolic dysfunction (DD) criteria (all p < 0.05). AoDi superimposed on key clinical variables significantly expanded C-statistic from 0.71 to 0.84 (p for ∆AUROC: < 0.001). These associations were broadly weaker for AoD. Conclusion: In our large asymptomatic Asian population, echocardiography-defined aortic root dilation was associated with aging and hypertension and were correlated modestly with computed tomography measures. A larger indexed aortic diameter appeared to be a useful indicator in identifying baseline abnormal diastolic dysfunction.

Prostate cancer (PC) is the most common carcinoma among men worldwide which results in 26% of leading causes of cancer-related death. However, the ideal and effective molecular marker remains elusive. CircRNA, initially observed in plant-infected viruses and Sendai virus in 1979, is generated from pre-mRNA back-splicing and comes in to play by adequate expression. The differential expression in prostate tissues compared with the control reveals the promising capacity in modulating processes including carcinogenesis and metastasis. However, the biological mechanisms of regulatory network in PC needs to systemically concluded. In this review, we enlightened the comprehensive studies on the definite mechanisms of circRNAs affecting tumor progression and metastasis. What's more, we validated the potential clinical application of circRNAs serving as diagnostic and prognostic biomarker. The discussion and analysis in circRNAs will broaden our knowledge of the pathogenesis of PC and further optimize the current therapies against different condition.

ispartof: AIAA Propulsion and Energy 2020 Forum ispartof: AIAA Propulsion and Energy 2020 Forum location:Virtual Event date:24 Aug - 28 Aug 2020 status: published