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Human mesenchymal stem/stromal cells (hMSCs) are a promising therapy for acute respiratory distress syndrome (ARDS) and other inflammatory conditions. While considerable research has focused on paracrine effects and mitochondrial transfer that improve lung fluid balance, hMSCs are well known to have immunomodulatory properties as well. Some of these immunomodulatory properties have been related to previously reported paracrine effectors such as indoleamine-2,3-dioxygenase (IDO), but these effects cannot fully account for cell-contact dependent immunomodulation. Here, we report that CD40 is upregulated on hMSCs under the same conditions previously reported to induce IDO. Further, CD40 transcription is also upregulated on hMSCs by ARDS pulmonary edema fluid but not by hydrostatic pulmonary edema fluid. Transcription of CD40, as well as paracrine effectors TSG6 and PTGS2 remained significantly upregulated for at least 12 hours after withdrawal of cytokine stimulation. Finally, induction of this immune phenotype altered the transdifferentiation of hMSCs, one of their hallmark properties. CD40 may play an important role in the immunomodulatory effects of hMSCs in ARDS and inflammation.

Background: Clustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population. Methods: We performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors. Results: Among all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65–79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk. Conclusion: Lifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk. [ABSTRACT FROM AUTHOR]

To maintain efficient myocardial function, optimal coordination between ventricular contraction and the arterial system is required. Exercise-based cardiac rehabilitation (CR) has been demonstrated to improve left ventricular (LV) function. This study aimed to investigate the impact of CR on ventricular-arterial coupling (VAC) and its components, as well as their associations with changes in LV function in patients with acute myocardial infarction (AMI) and preserved or mildly reduced ejection fraction (EF). Effective arterial elastance (EA) and index (EAI) were calculated from the stroke volume and brachial systolic blood pressure. Effective LV end-systolic elastance (ELV) and index (ELVI) were obtained using the single-beat method. The characteristic impedance (Zc) of the aortic root was calculated after Fourier transformation of both aortic pressure and flow waveforms. Pulse wave separation analysis was performed to obtain the reflection magnitude (RM). An exercise-based, outpatient cardiac rehabilitation (CR) program was administered for up to 6 months. Twenty-nine patients were studied. However, eight patients declined to participate in the CR program and were subsequently classified as the non-CR group. At baseline, E' velocity showed significant associations with EAI (beta -0.393; P = 0.027) and VAC (beta -0.375; P = 0.037). There were also significant associations of LV global longitudinal strain (LV GLS) with EAI (beta 0.467; P = 0.011). Follow-up studies after a minimum of 6 months demonstrated a significant increase in E' velocity (P = 0.035), improved EF (P = 0.010), and LV GLS (P = 0.001), and a decreased EAI (P = 0.025) only in the CR group. Changes in E' velocity were significantly associated with changes in EAI (beta -0.424; P = 0.033). Increased aortic afterload and VA mismatch were associated with a negative impact on both LV diastolic and systolic function. The outpatient CR program effectively decreased aortic afterload and improved LV diastolic and systolic dysfunction in patients with AMI and preserved or mildly reduced EF. [ABSTRACT FROM AUTHOR]

We analyzed complex networks generated by the threshold method in the Korean and Indian stock markets during the non-crisis period of 2004 and the crisis period of 2008, while varying the size of the system. To create the stock network, we randomly selected N stock indices from the market and constructed the network based on cross-correlation among the time series of stock prices. We computed the average shortest path length L and average clustering coefficient C for several ensembles of generated stock networks and found that both metrics are influenced by network size. Since L and C are affected by network size N, a direct comparison of graph measures between stock networks with different numbers of nodes could lead to erroneous conclusions. However, we observed that the dependency of network measures on N is significantly reduced when comparing larger networks with normalized shortest path lengths. Additionally, we discovered that the effect of network size on network measures during the crisis period is almost negligible compared to the non-crisis periods. [ABSTRACT FROM AUTHOR]

There has been a concern that angiotensin receptor blockers (ARB) may increase myocardial infarction (MI) in hypertensive patients compared with other classes of anti-hypertensive drugs. Angiotensin-converting enzyme inhibitor (ACEI) is recommended as a first-line inhibitor of renin-angiotensin system (RASI) in patients with acute MI (AMI), but ARB is also frequently used to control blood pressure. This study investigated the association of ARB vs. ACEI with the long-term clinical outcomes in hypertensive patients with AMI. Among patients enrolled in the nationwide AMI database of South Korea, the KAMIR-NIH, 4,827 hypertensive patients, who survived the initial attack and were taking ARB or ACEI at discharge, were selected for this study. ARB therapy was associated with higher incidence of 2-year major adverse cardiac events, cardiac death, all-cause death, MI than ACEI therapy in entire cohort. After propensity score-matching, ARB therapy was still associated with higher incidence of 2-year cardiac death (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.20–2.14; P = 0.001), all-cause death (HR, 1.81; 95% CI, 1.44–2.28; P < 0.001), and MI (HR, 1.76; 95% CI, 1.25–2.46; P = 0.001) than the ACEI therapy. It was concluded that ARB therapy at discharge in hypertensive patients with AMI was inferior to ACEI therapy with regard to the incidence of CD, all-cause death, and MI at 2-year. These data suggested that ACEI be a more appropriate RASI than ARB to control BP in hypertensive patients with AMI. [ABSTRACT FROM AUTHOR]

Background: Guidelines have recommended monitoring mean arterial pressure (MAP) and systolic arterial pressure (SAP) in cardiac arrest patients, but there has been relatively little regard for diastolic arterial pressure (DAP) and heart rate (HR). We aimed to determine the prognostic significance of hemodynamic parameters at all time points during targeted temperature management (TTM). Methods: We reviewed the SAP, DAP, MAP, and HR data in out-of-hospital cardiac arrest (OHCA) survivors from the prospective multicenter registry of 22 teaching hospitals. This study included 1371 patients who underwent TTM among 10,258 cardiac arrest patients. The hemodynamic parameters were recorded every 6 hours from the return of spontaneous circulation (ROSC) to 4 days. The risks of those according to time points during TTM were compared. Results: Of the included patients, 943 (68.8%) had poor neurological outcomes. The predictive ability of DAP surpassed that of SAP and MAP at all time points, and among the hemodynamic variables HR/DAP was the best predictor of the poor outcome. The risks in patients with DAP < 55 to 70 mmHg and HR > 70 to 100 beats/min were steeply increased for 2 days after ROSC and correlated with the poor outcome at all time points. Bradycardia showed lower risks only at 6 hours to 24 hours after ROSC. Conclusion: Hemodynamic parameters should be intensively monitored especially for 2 days after ROSC because cardiac arrest patients may be vulnerable to hemodynamic instability during TTM. Monitoring HR/DAP can help access the risks in cardiac arrest patients. [ABSTRACT FROM AUTHOR]

Polygenic risk scores (PRSs) have an important relevance to approaches for clinical usage in intracranial aneurysm (IA) patients. Hence, we aimed to develop IA-predicting PRS models including the genetic basis shared with acute ischemic stroke (AIS) in Korean populations. We applied a weighted PRS (wPRS) model based on a previous genome-wide association study (GWAS) of 250 IA patients in a hospital-based multicenter cohort, 222 AIS patients in a validation study, and 296 shared controls. Risk predictability was analyzed by the area under the receiver operating characteristic curve (AUROC). The best-fitting risk models based on wPRSs were stratified into tertiles representing the lowest, middle, and highest risk groups. The weighted PRS, which included 29 GWASs (p < 5×10−8) and two reported genetic variants (p < 0.01), showed a high predictability in IA patients (AUROC = 0.949, 95% CI: 0.933–0.966). This wPRS was significantly validated in AIS patients (AUROC = 0.842, 95% CI: 0.808–0.876; p < 0.001). Two-stage risk models stratified into tertiles showed an increased risk for IA (OR = 691.25, 95% CI: 241.77–1976.35; p = 3.1×10−34; sensitivity/specificity = 0.728/0.963), which was replicated in AIS development (OR = 39.76, 95% CI: 16.91–93.49; p = 3.1×10−17; sensitivity/specificity = 0.284/0.963). A higher wPRS for IA may be associated with an increased risk of AIS in the Korean population. These findings suggest that IA and AIS may have a shared genetic architecture and should be studied further to generate a precision medicine model for use in personalized diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls. Methods: Neuroinflammation was measured as the distribution volume ratio (DVR) of [11C]-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls. Results: Neuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of [11C]-(R)-PK11195 in FM patients demonstrated decreased neuroinflammation in the medulla (p < 0.005), left superior temporal gyrus (p < 0.005), and left amygdala (p = 0.020) compared with healthy controls. Conclusions: To the authors' knowledge, this report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using [11C]-(R)-PK11195 PET. The results suggested that abnormal neuroinflammation can be an important pathological factor in FM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM. [ABSTRACT FROM AUTHOR]