Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study.

BACKGROUND: The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk. METHODS: The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan-Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count. RESULTS: During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan-Meier curves. The adjusted HR (95% CI) for incident CVD in Q2-Q4, compared with Q1, was 1.47 (1.12-1.93), 1.91 (1.44-2.54) and 2.24 (1.63-3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease. CONCLUSIONS: The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.

Dilated perivascular spaces and steno-occlusive changes in children and adults with moyamoya disease.

BACKGROUND: Dilated perivascular spaces (DPVS), known as one of imaging markers in cerebral small vessel disease, may be found in patients with moyamoya disease (MMD). However, little is known about DPVS in MMD. The purpose of this study was to investigate the distribution pattern of dPVS in children and adults with MMD and determine whether it is related to steno-occlusive changes of MMD. METHODS: DPVS was scored in basal ganglia (BG) and white matter (WM) on T2-weighted imaging, using a validated 4-point semi-quantitative score. The degree of dPVS was classified as high (score > 2) or low (score ≤ 2) grade. The steno-occlusive changes on MR angiography (MRA) was scored using a validated MRA grading. Asymmetry of DPVS and MRA grading was defined as a difference of 1 grade or higher between hemispheres. RESULTS: Fifty-one patients with MMD (mean age 24.9 ± 21.1 years) were included. Forty-five (88.2%) patients had high WM-DPVS grade (degree 3 or 4). BG-DPVS was found in 72.5% of all patients and all were low grade (degree 1 or 2). The distribution patterns of DPVS degree in BG (P = 1.000) and WM (P = 0.767) were not different between child and adult groups. The asymmetry of WM-DPVS (26%) and MRA grade (42%) were significantly correlated to each other (Kendall's tau-b = 0.604, P < 0.001). CONCLUSIONS: DPVS of high grade in MMD is predominantly found in WM, which was not different between children and adults. The correlation between asymmetry of WM-DPVS degree and MRA grade suggests that weak cerebral artery pulsation due to steno-occlusive changes may affect WM-DPVS in MMD.

Development and Validation of Deep-Learning-Based Sepsis and Septic Shock Early Prediction System (DeepSEPS) Using Real-World ICU Data.

BACKGROUND: Successful sepsis treatment depends on early diagnosis. We aimed to develop and validate a system to predict sepsis and septic shock in real time using deep learning. METHODS: Clinical data were retrospectively collected from electronic medical records (EMRs). Data from 2010 to 2019 were used as development data, and data from 2020 to 2021 were used as validation data. The collected EMRs consisted of eight vital signs, 13 laboratory data points, and three demographic information items. We validated the deep-learning-based sepsis and septic shock early prediction system (DeepSEPS) using the validation datasets and compared our system with other traditional early warning scoring systems, such as the national early warning score, sequential organ failure assessment (SOFA), and quick sequential organ failure assessment. RESULTS: DeepSEPS achieved even higher area under receiver operating characteristic curve (AUROC) values (0.7888 and 0.8494 for sepsis and septic shock, respectively) than SOFA. The prediction performance of traditional scoring systems was enhanced because the early prediction time point was close to the onset time of sepsis; however, the DeepSEPS scoring system consistently outperformed all conventional scoring systems at all time points. Furthermore, at the time of onset of sepsis and septic shock, DeepSEPS showed the highest AUROC (0.9346). CONCLUSIONS: The sepsis and septic shock early warning system developed in this study exhibited a performance that is worth considering when predicting sepsis and septic shock compared to other traditional early warning scoring systems. DeepSEPS showed better performance than existing sepsis prediction programs. This novel real-time system that simultaneously predicts sepsis and septic shock requires further validation.

Early prediction of need for invasive mechanical ventilation in the neonatal intensive care unit using artificial intelligence and electronic health records: a clinical study.

BACKGROUND: Respiratory support is crucial for newborns with underdeveloped lung. The clinical outcomes of patients depend on the clinician's ability to recognize the status underlying the presented symptoms and signs. With the increasing number of high-risk infants, artificial intelligence (AI) should be considered as a tool for personalized neonatal care. Continuous monitoring of vital signs is essential in cardiorespiratory care. In this study, we developed deep learning (DL) prediction models for rapid and accurate detection of mechanical ventilation requirements in neonates using electronic health records (EHR). METHODS: We utilized data from the neonatal intensive care unit in a single center, collected between March 3, 2012, and March 4, 2022, including 1,394 patient records used for model development, consisting of 505 and 889 patients with and without invasive mechanical ventilation (IMV) support, respectively. The proposed model architecture includes feature embedding using feature-wise fully connected (FC) layers, followed by three bidirectional long short-term memory (LSTM) layers. RESULTS: A mean gestational age (GA) was 36.61 ± 3.25 weeks, and the mean birth weight was 2,734.01 ± 784.98 g. The IMV group had lower GA, birth weight, and longer hospitalization duration than the non-IMV group (P < 0.05). Our proposed model, tested on a dataset from March 4, 2019, to March 4, 2022. The mean AUROC of our proposed model for IMV support prediction performance demonstrated 0.861 (95%CI, 0.853-0.869). It is superior to conventional approaches, such as newborn early warning score systems (NEWS), Random Forest, and eXtreme gradient boosting (XGBoost) with 0.611 (95%CI, 0.600-0.622), 0.837 (95%CI, 0.828-0.845), and 0.0.831 (95%CI, 0.821-0.845), respectively. The highest AUPRC value is shown in the proposed model at 0.327 (95%CI, 0.308-0.347). The proposed model performed more accurate predictions as gestational age decreased. Additionally, the model exhibited the lowest alarm rate while maintaining the same sensitivity level. CONCLUSION: Deep learning approaches can help accurately standardize the prediction of invasive mechanical ventilation for neonatal patients and facilitate advanced neonatal care. The results of predictive, recall, and alarm performances of the proposed model outperformed the other models.

Corrected QTc interval combined with troponin value and mortality in acute ischemic stroke.

Background and Purpose: Cardiac biomarkers including, elevated troponin (ET) and prolonged heart rate-corrected QT (PQTc) interval on electrocardiography are known to frequent and have a prognostic significance in patients with acute ischemic stroke (AIS). However, it is still challenging to practically apply the results for appropriate risk stratification. This study evaluate whether combining ET and PQTc interval can better assess the long-term prognosis in AIS patients. Methods: In this prospectively registered observational study between May 2007 and December 2011, ET was defined as serum troponin-I ≥ 0.04 ng/ml and PQTc interval was defined as the highest tertile of sex-specific QTc interval (men ≥ 469 ms or women ≥ 487 ms). Results: Among the 1,668 patients [1018 (61.0%) men; mean age 66.0 ± 12.4 years], patients were stratified into four groups according to the combination of ET and PQTc intervals. During a median follow-up of 33 months, ET (hazard ratio [HR]: 4.38, 95% confidence interval [CI]: 2.94-6.53) or PQTc interval (HR: 1.53, 95% CI: 1.16-2.01) alone or both (HR: 1.77, 95% CI: 1.16-2.71) was associated with increased all-cause mortality. Furthermore, ET, PQTc interval alone or both was associated with vascular death, whereas only ET alone was associated with non-vascular death. Comorbidity burden, especially atrial fibrillation and congestive heart failure, and stroke severity gradually increased both with troponin value and QTc-interval. Conclusions: In patients with AIS, combining ET and PQTc interval on ECG enhances risk stratification for long-term mortality while facilitating the discerning ability for the burden of comorbidities and stroke severity.

Papilledema and venous stasis in patients with cerebral venous and sinus thrombosis.

BACKGROUND: Cerebral venous and sinus thrombosis (CVST) can cause increased intracranial pressure, often leading to papilledema. In this study, we investigated the association between papilledema and venous stasis on susceptibility weighted imaging (SWI) in CVST. METHODS: Patients with CVST between 2008 and 2020 were reviewed. Patients without fundoscopic examination or SWI were excluded in this study. Venous stasis was evaluated and scored for each cerebral hemisphere: each hemisphere was divided into 5 regions according to the venous drainage territories (superior sagittal sinus, Sylvian veins, transverse sinus and vein of Labbé, deep cerebral veins, and medullary veins) and 1 point was added if venous prominence was confirmed in one territory on SWI. The venous stasis score on SWI between cerebral hemispheres with and without papilledema was compared. RESULTS: Eight of 19 patients with CVST were excluded because of the absence of fundoscopic examination or SWI. Eleven patients (26.5 ± 2.1 years) were included in this study. Papilledema was identified in 6 patients: bilateral papilledema in 4 patients and unilateral papilledema in 2 patients. The venous stasis score on SWI was significantly higher (P = 0.013) in the hemispheres with papilledema (median, 4.0; 95% CI, 3.038-4.562) than in the hemispheres without papilledema (median, 2.5; 95% CI, 0.695-2.805). CONCLUSIONS: This study shows that higher score of venous stasis on SWI is associated with papilledema. Therefore, the venous stasis on SWI may be an imaging surrogate marker of increased intracranial pressure in patients with CVST.

Explanatory Power and Prognostic Implications of Factors Associated with Troponin Elevation in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: We investigated the impact of comorbidity burden on troponin elevation, with separate consideration of neurological conditions, in patients with acute ischemic stroke (AIS). METHODS: This prospective, observational cohort study consecutively enrolled patients with AIS for 2 years. Serum cardiac troponin I was repeatedly measured, and disease-related biomarkers were collected for diagnosis of preassigned comorbidities, including atrial fibrillation (AF), ischemic heart disease (IHD), myocardial hypertrophy (MH), heart failure (HF), renal insufficiency (RI), and active cancer. The severity of neurological deficits and insular cortical ischemic lesions were assessed as neurological conditions. Adjusted associations between these factors and troponin elevation were determined using a multivariate ordinal logistic regression model and area under the receiver operating characteristic curve (AUC). Cox proportional hazards model was used to determine the prognostic significance of comorbidity beyond neurological conditions. RESULTS: Among 1,092 patients (66.5±12.4 years, 63.3% male), 145 (13.3%) and 335 (30.7%) had elevated (≥0.040 ng/mL) and minimally-elevated (0.040-0.010 ng/mL) troponin, respectively. In the adjusted analysis, AF, MH, HF, RI, active cancer, and neurological deficits were associated with troponin elevation. The multivariate model with six comorbidities and two neurological conditions exhibited an AUC of 0.729 (95% confidence interval [CI], 0.698-0.759). In Cox regression, AF, IHD, and HF were associated with adverse cardio-cerebrovascular events, whereas HF and active cancer were associated with mortality. CONCLUSION: Troponin elevation in patients with AIS can be explained by the burden of comorbidities in combination with neurological status, which explains the prognostic significance of troponin assay.

Usefulness of cone-beam computed tomography to predict residual stenosis after carotid artery stenting.

OBJECTIVES: The long-term durability of carotid artery stenting (CAS) may be determined by various factors; however, residual stenosis is a known risk factor for in-stent restenosis. The authors of this article utilized cone-beam computed tomography (CBCT) in angiosuite to investigate plaque features affecting the character and quality of stent expansion after CAS. METHODS: Forty-two CAS cases with both pre- and post-CAS CBCT evaluations were included in this retrospective analysis. Five features derived from pre-CAS images were tested: (1) eccentricity, (2) overballoon, (3) maximum plaque thickness, (4) calcification barrier, and (5) stenotic degree. For post-CAS CBCT, stent configuration was assessed if the stent was expanded and oval or round in shape as well as outward or inward in orientation. Variables were tested if they were associated with oval expansion, outward expansion, and 20% residual stenosis after CAS. RESULTS: Oval or outward expansion is directly related to residual stenosis. The oval expansion was associated with maximum plaque thickness, and outward expansion was associated with the presence of a calcification barrier. Variables related to > 20% residual stenosis were the maximum plaque thickness, calcification barrier, and pre-CAS stenotic degree. CONCLUSIONS: CBCT for carotid stenosis may provide valuable information about plaque features, especially calcification features that may interfere with the angioplasty effect, as well as the characteristics and quality of stent expansion. Residual stenosis > 20% was associated with calcification barrier, maximum plaque thickness, and pre-CAS stenotic degree.

Culturable Endophytes Associated with Soybean Seeds and Their Potential for Suppressing Seed-Borne Pathogens.

Seed-borne pathogens in crops reduce the seed germination rate and hamper seedling growth, leading to significant yield loss. Due to the growing concerns about environmental damage and the development of resistance to agrochemicals among pathogen populations, there is a strong demand for eco-friendly alternatives to synthetic chemicals in agriculture. It has been well established during the last few decades that plant seeds harbor diverse microbes, some of which are vertically transmitted and important for plant health and productivity. In this study, we isolated culturable endophytic bacteria and fungi from soybean seeds and evaluated their antagonistic activities against common bacterial and fungal seed-borne pathogens of soybean. A total of 87 bacterial isolates and 66 fungal isolates were obtained. Sequencing of 16S rDNA and internal transcribed spacer amplicon showed that these isolates correspond to 30 and 15 different species of bacteria and fungi, respectively. Our antibacterial and antifungal activity assay showed that four fungal species and nine bacterial species have the potential to suppress the growth of at least one seed-borne pathogen tested in the study. Among them, Pseudomonas koreensis appears to have strong antagonistic activities across all the pathogens. Our collection of soybean seed endophytes would be a valuable resource not only for studying biology and ecology of seed endophytes but also for practical deployment of seed endophytes toward crop protection.

Systemic inflammatory markers of persistent cerebral edema after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH. METHODS: Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early brain edema score' (SEBES). SEBES ≤ 2 and SEBES ≥ 3 were considered good and poor grade, respectively. Serum samples from the same subject cohort were collected at 4 time periods (at < 24 h [T1], at 24 to 48 h [T2]. 3-5 days [T3] and 6-8 days [T4] post-admission) and concentration levels of 17 cytokines (implicated in peripheral inflammatory processes) were measured by multiplex immunoassay. Multivariable logistic regression analyses were step-wisely performed to identify cytokines independently associated with persistent CE adjusting for covariables including age, sex and past medical history (model 1), and additional inclusion of clinical and radiographic severity of SAH and treatment modality (model 2). RESULTS: Of the 135 patients enrolled in the study, 21 of 135 subjects (15.6%) showed a persistently poor SEBES grade. In multivariate model 1, higher Eotaxin (at T1 and T4), sCD40L (at T4), IL-6 (at T1 and T3) and TNF-α (at T4) were independently associated with persistent CE. In multivariate model 2, Eotaxin (at T4: odds ratio [OR] = 1.019, 95% confidence interval [CI] = 1.002-1.035) and possibly PDGF-AA (at T4), sCD40L (at T4), and TNF-α (at T4) was associated with persistent CE. CONCLUSIONS: We identified serum cytokines at different time points that were independently associated with persistent CE. Specifically, persistent elevations of Eotaxin is associated with persistent CE after SAH.

The Spot Sign and Intraventricular Hemorrhage are Associated with Baseline Coagulopathy and Outcome in Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is the second most prevalent subtype of stroke and has high mortality and morbidity. The utility of radiographic features to predict secondary brain injury related to hematoma expansion (HE) or increased intracranial pressure has been highlighted in patients with ICH, including the computed tomographic angiography (CTA) spot sign and intraventricular hemorrhage (IVH). Understanding the pathophysiology of spot sign and IVH may help identify optimal therapeutic strategies. We examined factors related to the spot sign and IVH, including coagulation status, hematoma size, and location, and evaluated their prognostic value in patients with ICH. METHODS: Prospectively collected data from a single center between 2012 and 2015 were analyzed. Patients who underwent thromboelastography within 24 h of symptom onset and completed follow-up brain imaging and CTA within 48 h after onset were included for analysis. Multivariate logistic regression analyses were performed to identify determinants of the spot sign and IVH and their predictive value for HE, early neurological deterioration (END), in-hospital mortality, and functional outcome at discharge. RESULTS: Of 161 patients, 50 (31.1%) had a spot sign and 93 (57.8%) had IVH. In multivariable analysis, the spot sign was associated with greater hematoma volume (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.00-1.03), decreased white blood cell count (OR 0.88; 95% CI 0.79-0.98), and prolonged activated partial thromboplastin time (OR 1.14; 95% CI 1.06-1.23). IVH was associated with greater hematoma volume (OR 1.02; 95% CI 1.01-1.04) and nonlobar location of hematoma (OR 0.23; 95% CI 0.09-0.61). The spot sign was associated with greater risk of all adverse outcomes. IVH was associated with an increased risk of END and reduced HE, without significant impact on mortality or functional outcome. CONCLUSIONS: The spot sign and IVH are associated with specific hematoma characteristics, such as size and location, but are related differently to coagulation status and clinical course. A combined analysis of the spot sign and IVH can improve the understanding of pathophysiology and risk stratification after ICH.

Capmatinib attenuates lipogenesis in 3T3-L1 adipocytes through an adenosine monophosphate-activated protein kinase-dependent pathway.

Recently, there is a rapid increase in the incidence of obesity, a condition for which there are no effective therapeutic agents. Capmatinib (CAP), a novel mesenchymal-to-epithelial transition inhibitor, is reported to attenuate pro-inflammatory mediators and oxidative stress. In this study, the effects of CAP on lipogenesis in the adipocytes were examined. Treatment with CAP dose-dependently suppressed lipid accumulation in, and differentiation of, and increased lipolysis in, 3T3-L1 adipocytes. Additionally, CAP treatment augmented adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and FNDC5 expression in the adipocytes. Transfection with si-AMPK or si-FNDC5 mitigated the CAP-induced suppression of lipogenesis and enhanced lipolysis. Furthermore, transfection with si-FNDC5 mitigated the CAP-induced phosphorylation of AMPK. These results suggest that the anti-obesity effect of CAP is mediated through the irisin/AMPK pathway and that CAP is a novel therapeutic agent for obesity.

Prognostic Significance of Prolonged Corrected QT Interval in Acute Ischemic Stroke.

Background and Purpose: The aim of this study was to determine the relationship between the heart rate-corrected QT (QTc) interval and the risk of incident long-term mortality in patients with acute ischemic stroke (AIS), considering the impact of sex differences on clinical characteristics, outcomes, and QTc intervals. Methods: We analyzed prospectively registered data included patients with AIS who visited the emergency room within 24 h of stroke onset and underwent routine cardiac testing, such as measurements of cardiac enzymes and 12-lead ECG. QTc interval was corrected for heart rate using Fridericia's formula and was stratified by sex-specific quartiles. Cox proportional hazards models were used to examine the association between baseline QTc interval and incident all-cause death. Results: A total of 1,668 patients with 1,018 (61.0%) men and mean age 66.0 ± 12.4 years were deemed eligible. Based on the categorized quartiles of the QTc interval, cardiovascular risk profile, and stroke severity increased with prolonged QTc interval, and the risk of long-term mortality increased over a median follow-up of 33 months. Cox proportional hazard model analysis showed that the highest quartile of QTc interval (≥479 msec in men and ≥498 msec in women; hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.07-2.08) was associated with all-cause death. Furthermore, dichotomized QTc interval prolongation, defined by the highest septile of the QTc interval (≥501 ms in men and ≥517 m in women: HR: 1.33, 95% CI: 1.00-1.80) was significantly associated with all-cause mortality after adjusting for all clinically relevant variables, such as stroke severity. Conclusions: Prolonged QTc interval was associated with increased risk of long-term mortality, in parallel with the increasing trend of prevalence of cardiovascular risk profiles and stroke severity, across sex differences in AIS patients.

Inverse association between triglyceride glucose index and muscle mass in Korean adults: 2008-2011 KNHANES.

BACKGROUND: Since sarcopenia is an important risk factor for falls or cardiovascular disease, early detection and prevention of sarcopenia are being increasingly emphasized. Emerging evidence has indicated relationships between sarcopenia, insulin resistance, and inflammation. The triglyceride glucose (TyG) index, a novel surrogate marker of insulin resistance and systemic inflammation, has not yet been shown to be associated with sarcopenia. This study aimed to examine the relationship between the TyG index and muscle mass in Korean adults. METHODS: This study included 15,741 non-diabetic adults over 19 years old using data from the 2008-2011 Korea National Health and Nutrition Examination Survey. Participants were divided into three groups according to tertiles of the TyG index. A low skeletal muscle mass index (LSMI) was defined by the Foundation for the National Institutes of Health Sarcopenia Project criteria. A weighted multivariate logistic regression model was used to analyze relationships between TyG index tertiles and LSMI. RESULTS: The ORs (95% CIs) for LSMI in the second and third TyG tertiles, compared to the first tertile, were 1.463 (1.131-1.892) and 1.816 (1.394-2.366), respectively, after adjusting for confounding factors. Higher TyG index values were also associated with increased odds of LSMI in adults under 65 years who did not exercise regularly, who consumed less than 30 g of alcohol per day, who did not currently smoke, and who ate less than 1.5 g of protein/kg/day. CONCLUSION: The TyG index was significantly and positively associated with LSMI in Korean adults.

Effects of dabigatran and rivaroxaban on stroke severity according to the results of routine coagulation tests.

INTRODUCTION: Prior use of direct oral anticoagulants has been associated with reduced stroke severity in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the impact of prothrombin time (PT) and activated partial thromboplastin time (aPTT) on stroke severity in patients who were receiving dabigatran or rivaroxaban at the time of stroke onset. MATERIALS AND METHODS: We enrolled 107 patients with NVAF who developed acute ischemic stroke while on dabigatran or rivaroxaban and presented within 24 hours to nine hospitals between January 2014 and December 2018. The results of PT and aPTT assays were obtained within 24 hours of stroke onset in all patients. We analyzed PT and aPTT in relation to stroke severity and ischemic lesion volume using correlation and multivariable regression analyses. RESULTS: Of the 107 patients included, 46 (43.0%) were on dabigatran and 61 (57.0%) were on rivaroxaban. In patients with prior dabigatran use, while aPTT was inversely correlated with admission National Institutes of Health Stroke Scale (NIHSS) score (r = -0.369, p = 0.012) and ischemic lesion volume (r = -0.480, p = 0.005), there was no correlation between PT and either of these variables. Multivariable analysis confirmed the existence of a significant independent inverse relationship between aPTT and NIHSS score at admission (B, -0.201; 95% confidence interval [CI], -0.370 to -0.032; p = 0.005) and between aPTT and ischemic lesion volume (B, -0.076; 95% CI, -0.130 to -0.023; p = 0.007). In patients with prior rivaroxaban use, neither PT nor aPTT was associated with admission NIHSS score or ischemic lesion volume in the correlation and multivariable analyses. CONCLUSIONS: In patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity.

Administration of kynurenic acid reduces hyperlipidemia-induced inflammation and insulin resistance in skeletal muscle and adipocytes.

Kynurenic acid (KA), an endogenous product of L-tryptophan metabolism in the kynurenine pathway, regulates adipose tissue energy homeostasis and inflammation. However, its role in palmitate-induced insulin resistance and detailed underlying mechanisms in skeletal muscles and adipose tissues are unclear. Herein, we report that KA ameliorated palmitate-induced inflammation and insulin resistance in differentiated C2C12 and 3T3-L1 cell lines as well as soleus skeletal muscle and subcutaneous adipose tissues in mice. Palmitate-induced inflammatory markers, such as nuclear factor κB translocation, inhibitory κBα phosphorylation, pro-inflammatory cytokine expression, and impaired insulin signaling, were markedly attenuated by KA both in vitro and in vivo. KA significantly increased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 6 (SIRT6) expressions in C2C12 myocytes and 3T3-L1 adipocytes and skeletal muscle and adipose tissues of mice. siRNA-mediated AMPK or SIRT6 inhibition significantly mitigated the suppressive effects of KA on palmitate-induced inflammation and insulin resistance. KA significantly stimulated expression of genes involved in fatty acid oxidation in C2C12 myocytes and skeletal muscle of mice. Moreover, KA inhibits lipogenesis in 3T3-L1 adipocytes. AMPK or SIRT6 siRNA markedly reversed these changes. The siRNA targeting Gpr35 abrogated the effects of KA on AMPK phosphorylation in C2C12 myocytes and 3T3-L1 adipocytes, except SIRT6 expression. It has therefore been shown that KA could potentially alleviate inflammation and insulin resistance in skeletal muscle and adipose tissues through Gpr35/AMPK and SIRT6-mediated pathways.

Phylogenetic Positioning of a Strongyloides stercoralis Isolate Recovered from a Korean Patient and Comparison with Other Asian Isolates.

Strongyloidiasis is caused by Strongyloides stercoralis and is one of the most neglected tropical diseases in tropical and subtropical regions. Although several strongyloidiasis cases have been reported in Korea, genetic analysis of Korean isolates is still incomplete. In this study, a parasite was isolated from a 61-year-old man diagnosed with strongyloidiasis during the treatment of lymphoma on his retroperitoneal lymph node. Diffuse symmetric wall thickening from the ascending to descending colon and a nematode-infected intestine was observed following microscopic examination. Genomic DNA was isolated from a patient tissue block, and S. stercoralis was identified by PCR and sequencing (18S rDNA). In order to determine phylogenetic location of a Korean isolate (named KS1), we analyzed cox1 gene (500-bp) and compared it with that from 47 previous S. stercoralis isolates (28 human isolates and 19 canid isolates) from Asian countries. Our results showed that phylogenetic tree could clearly be divided into 5 different groups according to hosts and regions. KS1 was most closely related with the Chinese isolates in terms of genetic distance.

Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.

BACKGROUND: Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions. METHODS: Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods (< 24 h, 24-48 h, 3-5 days, and 6-8 days after SAH) and concentration levels of 41 cytokines were measured by multiplex immunoassay. Logistic regression analysis was used to identify cytokines associated with DCI and poor functional outcomes. Correlation networks were constructed to identify cytokine clusters. RESULTS: Of the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3 months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1α. Poor functional outcome was associated with increased levels of IL-6 and MCP-1α. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes. CONCLUSIONS: Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.

Protectin DX ameliorates palmitate-induced hepatic insulin resistance through AMPK/SIRT1-mediated modulation of fetuin-A and SeP expression.

The role as well as the molecular mechanisms of protectin DX (PDX) in the prevention of hepatic insulin resistance, a hallmark of type 2 diabetes, remains unknown. Therefore, the present study was designed to explore the direct impact of PDX on insulin resistance and to investigate the expression of fetuin-A and selenoprotein P (SeP), hepatokines that are involved in insulin signalling, in hepatocytes. Human serum levels of PDX as well as fetuin-A and SeP were determined by high-performance liquid chromatography (HPLC). Human primary hepatocytes were treated with palmitate and PDX. NF-κB phosphorylation as well as expression of insulin signalling associated genes and hepatokines were determined by Western blotting analysis. FOXO1 binding levels were measured by quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si) RNA-mediated gene suppression. Serum PDX levels were significantly (P < 0.05) downregulated, whereas serum fetuin-A and SeP levels were increased (P < 0.05) in obese subjects compared with healthy subjects. In in vitro experiments, PDX treatment increased AMP-activated protein kinase (AMPK) phosphorylation and SIRT1 expression and attenuated palmitate-induced fetuin-A and SeP expression and insulin resistance in hepatocytes. AMPK or SIRT1 siRNA mitigated the suppressive effects of PDX on palmitate-induced fetuin-A through NF-κB and SeP expression linked to FOXO1 and insulin resistance. Recombinant fetuin-A and SeP reversed the suppressive effects of fetuin-A and SeP expression on palmitate-mediated impairment of insulin signalling. The current finding provides novel insight into the underlying mechanism linking hepatokines to the pathogenesis of hepatic insulin resistance.