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BACKGROUND AND AIMS Fat accumulation results from increased fat absorption and/or defective fat metabolism. Currently, the lipid-sensing nuclear receptor that controls fat utilization in hepatocytes is elusive. Liver X receptor alpha (LXRα) promotes accumulation of lipids through the induction of several lipogenic genes. However, its effect on lipid degradation is open for study. Here, we investigated the inhibitory role of LXRα in autophagy/lipophagy in hepatocytes and the underlying basis. APPROACH AND RESULTS In LXRα knockout mice fed a high-fat diet, or cell models, LXRα activation suppressed the function of mitochondria by inhibiting autophagy/lipophagy and induced hepatic steatosis. Gene sets associated with "autophagy" were enriched in hepatic transcriptome data. Autophagy flux was markedly augmented in the LXRα knockout mouse liver and primary hepatocytes. Mechanistically, LXRα suppressed autophagy-related 4B cysteine peptidase (ATG4B) and Rab-8B, responsible for autophagosome and -lysosome formation, by inducing let-7a and microRNA (miR)-34a. Chromatin immunoprecipitation assay enabled us to find LXRα as a transcription factor of let-7a and miR-34a. Moreover, 3' untranslated region luciferase assay substantiated the direct inhibitory effects of let-7a and miR-34a on ATG4B and Rab-8B. Consistently, either LXRα activation or the let-7a/miR-34a transfection lowered mitochondrial oxygen consumption rate and mitochondrial transmembrane potential and increased fat levels. In obese animals or nonalcoholic fatty liver disease (NAFLD) patients, let-7a and miR-34a levels were elevated with simultaneous decreases in ATG4B and Rab-8B levels. CONCLUSIONS LXRα inhibits autophagy in hepatocytes through down-regulating ATG4B and Rab-8B by transcriptionally activating microRNA let-7a-2 and microRNA 34a genes and suppresses mitochondrial biogenesis and fuel consumption. This highlights a function of LXRα that culminates in the progression of liver steatosis and steatohepatitis, and the identified targets may be applied for a therapeutic strategy in the treatment of NAFLD.

Background: Atrial septal defect (ASD) is the most common congenital heart disease. However, the details of cardiac chamber remodeling after surgery are not well known, although this is an important issue that should be analyzed to understand long-term outcomes. Methods: Between November 2017 and January 2019, cardiac magnetic resonance imaging was performed preoperatively, at a 1-month postoperative follow-up, and at a 1-year postoperative follow-up. Cardiac chamber volume, valve regurgitation volume, and ejection fraction were measured as functions of time. Results: Thirteen patients (10 men and 3 women) were included. The median age at surgery was 51.4 years. The preoperative median ratio of flow in the pulmonary and systemic circulation was 2.3. The preoperative mean right ventricular (RV) end-diastolic volume index (EDVi) and RV end-systolic volume index (ESVi) had significantly decreased at the 1-month postoperative follow-up (p

Activation of sterol regulatory element-binding protein 1 (SREBP-1), a master lipogenic transcription factor, is associated with cancer metabolism and metabolic disorders. Neddylation, the process of adding NEDD8 to its substrate, contributes to diverse biological processes. Here, we identified SREBP-1 as a substrate for neddylation by UBC12 and explored its impact on tumor aggressiveness. In cell-based assays, SREBP-1 neddylation prolonged SREBP-1 stability with a decrease in ubiquitination. Consequently, NEDD8 overexpression facilitated proliferation, migration, and invasion of SK-Hep1 liver tumor cells. MLN4924 (an inhibitor of the NEDD8-activating enzyme-E1) treatment or UBC12 knockdown prevented SREBP-1 neddylation and tumor cell phenotype change. This effect was corroborated in an in vivo xenograft model. In human specimens, SREBP-1, UBC12, and NEDD8 were all upregulated in hepatocellular carcinoma (HCC) compared to nontumorous regions. Moreover, SREBP-1 levels positively correlated with UBC12. In GEO database analyses, SREBP-1 levels were greater in metastatic HCC samples accompanying UBC12 upregulation. In HCC analysis, tumoral SREBP-1 and UBC12 levels discriminated overall patient survival rates. Additionally, MLN4924 treatment destabilized SREBP-1 in MDA-MB-231 breast cancer cells and in the tumor cell xenograft. SREBP-1 and UBC12 were also highly expressed in human breast cancer tissues. Moreover, most breast cancers with lymph node metastasis displayed predominant SREBP-1 and UBC12 expressions, which compromised overall patient survival rates. In summary, SREBP-1 is neddylated by UBC12, which may contribute to HCC and breast cancer aggressiveness through SREBP-1 stabilization, and these events can be intervented by MLN4924 therapy. Our findings may also provide potential reliable prognostic markers for tumor metastasis.

A prosthesis with a self-expanding nitinol frame firmly incorporates into the aortic wall and thus is difficult to explant. We introduce a novel technique that simplifies explantation.

Left ventricular lipoma is a rare intracardiac tumour that is usually resected through sternotomy to effectively explore the left ventricular cavity. We introduce a simple technique to expose the left ventricular cavity and resect the intraventricular lipoma using a rolled up flexible ruler through right mini-thoracotomy. Imaging studies and gross and microscopic photography of intraventricular lipoma are presented in this report.

The muscular discontinuities at the pulmonary vein (PV)–left atrial (LA) junction are known. The high-density mapping may help to find the muscular discontinuity. This study evaluated the efficacy of a partial antral ablation for a pulmonary vein (PV) isolation using high density (HD) mapping. A total of 60 drug-refractory atrial fibrillation (AF) patients undergoing catheter ablation were enrolled. The detailed activation mapping of each PV and LA junction was performed using an HD mapping system, and each PV segment’s activation pattern was classified into a “directly-activated from the LA” or “passively-activated from an adjacent PV segment” pattern. The antral ablations were performed at the directly-activated PV segments only when the PV had “passively-activated segments”. If the PV did not contain passively-activated segments, a circumferential antral ablation was performed on those PVs. A “successful partial antral ablation” was designated if the electrical isolation of targeted PV was achieved by ablation at the directly-activated segments only. If the isolation was not achieved even though all directly-activated segments were ablated, a “failed partial antral ablation” was designated, and then a circumferential ablation was performed. Among 240 PVs, passively-activated segments were observed in 140 (58.3%) PVs. Both inferior PVs had more passively-activated segments than superior PVs, and the posteroinferior segments had the highest proportion of passive activation. The overall rate of successful partial antral ablation was 85%. The atrial tachyarrhythmia recurrence was observed in 10 patients (16.7%) at 1-year. HD mapping allowed the evaluation of the detailed activation patterns of the PVs, and passively-activated segments may represent muscular discontinuity. Partial antral ablation of directly-activated antral segments only was feasible and effective for a PVI.

A mild-to-moderate aortic root aneurysm might be overlooked during the assessment of the donor heart. The use of the Z-score in such cases may be helpful in guiding clinical decision-making. To make a diagnosis of genetic aortopathy, a genetic panel study and matching with clinical criteria such as Ghent nosology are essential. Valve-sparing root reimplantation may be a viable option in cases with aortic root aneurysm developing after heart transplant.

Background The injured liver loses normal function, with concomitant decrease of key identity genes. Super-enhancers contribute to mammalian cell identity. Here, we identified core transcription factors (TFs) that are active in hepatocytes, using genome-wide analysis and hierarchical ordering of super-enhancer distribution. Methods Expression of core TFs was assessed in a cohort of patients with hepatitis or cirrhosis and animal models. Quantitative PCR, chromatin immunoprecipitation assays, and hydrodynamic gene delivery methods were used to assess gene regulation and hepatocyte viability. RNA-sequencing data were generated to investigate the role of LRH1 in hepatocyte protection from injury. Results Network analysis of super-enhancer-associated gene interactions and expression arrays for cohorts of patients with hepatitis and cirrhosis enabled us to identify a super-enhancer-associated network, and LRH1, HNF4α, PPARα, and RXRα as core TFs. In mouse models, expression of core TFs was robustly inhibited by single and multiple challenge(s) with liver toxicant. RNA-seq analysis revealed changes in expression in the super-enhancer-associated genes sensitively biased toward repression by intoxication. LRH1 gene delivery prevented the loss of hepatic super-enhancer-associated signaling circuitry in toxicant-challenged mice, and protected the liver from injury, indicating the role of LRH1 in hepatocyte identity and viability. In hepatocytes, overexpression of each core TF promoted induction of other TFs. Conclusion Overall, this study identified LRH1-driven pathway as a circuitry responsible for hepatocyte identity by using cistromic analysis, improving our understanding of liver pathophysiology and identifying novel therapeutic targets.

Background: Takotsubo syndrome following cardiac surgery is a rare occurrence. However, early diagnosis is essential to prevent treatment which could increase the left ventricular outflow tract pressure gradient in patients with Takotsubo syndrome, and lead to cardiogenic shock. Therefore, our study aimed to identify the incidence of Takotsubo syndrome after cardiopulmonary bypass and the associated risk factors and prognosis.Methods: We retrospectively studied 5,773 patients who underwent cardiopulmonary bypass between February 2007 and July 2017. Among these, Takotsubo syndrome was diagnosed in 52 (0.9%). To evaluate the risk factors for Takotsubo syndrome, 104 of the remaining 5,721 patient were randomly selected as the control group (1:2 ratio). Univariate and multivariate logistic regression analyses were used for risk factor analysis. Results: Majority of patients (69.2%) in the Takotsubo syndrome group underwent mitral valve surgery, compared to 32.7% in the control group. The following risk factors of Takotsubo syndrome were identified: atrio-ventricular valve surgery (odds ratio (OR),10.5; 95% confidence interval (CI), 2.6-42.5; P=0.001); and the immediate postoperative use of epinephrine (OR, 3.3; 95%CI, 1.0-10.7; P=0.05) and dobutamine (OR, 4.8; 95%CI, 1.72-13.3; P=0.003). Hypertension was a significant protective factor against Takotsubo syndrome following cardiac surgery (OR, 0.22; 95%CI, 0.06-0.73; P=0.01).Conclusions: Takotsubo syndrome following cardiac surgery is rare. Immediate postoperative use of epinephrine and doputamine, as well as atrio-ventricular valve surgery were factors associated with the development of Takotsubo syndrome.

INTRODUCTION Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) catheter ablation. However, a PVI alone has been considered insufficient for persistent AF. This study aimed to evaluate the efficacy of persistent AF ablation targeting complex fractionated atrial electrogram (CFAE) areas within low voltage zones identified by high-resolution mapping in addition to the PVI. METHODS We randomized 50 patients (mean age 58.4 ± 9.5 years old, 86.0% males) with persistent AF to a PVI + CFAE group and PVI only group in a 1:1 ratio. CFAE and voltage mapping was performed simultaneously using a Pentaray Catheter with the CARTO3 CONFIDENSE module (Biosense Webster, CA, USA). The PVI + CFAE group, in addition to the PVI, underwent ablation targeting low voltage areas (

Background and Purpose Hepatocellular carcinoma (HCC) is the second most common cancer worldwide, demonstrating aggressiveness and mortality more frequently in men than in women. Despite reports regarding the inhibitory ability of estrogen receptor alpha (ERα, ESR1) in certain cancer progression, targets and the basis of underlying gender disparity in HCC worsening remain elusive. Experimental Approach Human HCC samples were used for immunoblottings and immunohistochemistry. Estradiol (E2) was treated to HCC cell lines and were evaluated by immunoblottings, polymerase chain reaction, immunofluorescence, and live imaging. Key Results Here, we report the ability of ERα to transcriptionally inhibit G protein subunit alpha 12 (Gα12). First, using human samples and public database, the expression of ERα and Gα12 in HCC was examined. Then, quantitative real-time PCR, chromatin immunoprecipitation-assay, luciferase assay, and immunoblottings confirmed the inhibitory ability of ERα on Gα12 and EMT. Additionally, we found microRNA-141 and -200a as downstream targets of the Gα12 signaling axis for cancer malignancy regulation under the control of ERα. As for in-depth mechanism, PTP4A1 was found to be directly inhibited by microRNA-141 and -200a. Gα12 and PTP4A1 promoted epithelial-mesenchymal transition, as well as mesenchymal to amoeboidal transition, antagonized by ERα modulations. Conclusion and Implications The identified targets and ESR1 levels inversely correlated in human specimens, as well as with sex-biased survival rates of HCC patients. Collectively, ERα-dependent repression of Gα12 and consequent changes in the Gα12 signaling may explain the gender disparity in HCC, providing pharmacological clues for the control of metastatic HCC.

Background We aimed to evaluate the effect of limited volume of hydroxyethyl starch (HES) administration on postoperative renal function in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). Methods One thousand six hundred fifty-seven patients undergoing cardiac surgery under CPB over two years were included. The patients were divided according to the amount of HES administrated during the first 2 days post-surgery; moderate dose HES (≥20 ml/kg) versus low dose HES ( Results Incidence of acute kidney injury (AKI) was higher in the moderate HES group (p = .02). However, new renal replacement therapy (RRT) (P = .30) and early mortality (p = .97) was similar between the groups. When adjusted, the moderate HES use was associated with AKI (OR, 1.66; 95% CI, 1.12–2.44; p = .01), but did not increase the risk of new RRT (OR, 1.27; 95% CI, 0.71–2.18; p = .40) or early mortality (HR, 0.73; 95% CI, 0.29–1.81; p = .50). Conclusions The moderate dose administration of HES (≥20 ml/kg) in the postoperative period following cardiac surgery might be associated with the risk of AKI. However, it was not associated with serious adverse outcomes such as new RRT or mortality. Further randomized controlled studies are needed to validate study results.

Highlights • 19 patients (24%) were treated with ECMO among 80 mechanical ventilation-supported patients. • Weaning and mortality rate of ECMO was 42% (8/19) and 58% (10/19), respectively. • Despite the known low case-fatality rate of COVID-19, mortality rate of ECMO-treated patients was substantial., Background The COVID-19 pandemic has caused an epidemic of critical patients, some of whom have been treated with extracorporeal membrane oxygenation (ECMO). This purpose of study is to describe the clinical course of COVID-19 patients treated with ECMO. Methods A multicentered study of critical patients with COVID-19 treated at six hospitals in Daegu was conducted between January and April 2020. Results Among the 80 patients receiving mechanical ventilation support, 19 (24%) were treated with ECMO included (median age 63.0 years). Eight of the 19 patients (42%) were weaned off ECMO (9.8 days, IQR 7.0-13.7). Among them, four patients were also weaned off mechanical ventilation (33.4 days, IQR 29.3 - 35.7), three were still receiving mechanical ventilation (50.9 days), and one expired after ECMO weaning. According to the univariate analysis, the factor that was associated with successful ECMO weaning was vitamin B12 treatment (p = 0.028). Conclusions During the COVID-19 epidemic, ECMO weaning and mortality rates were 42% and 58%, respectively.

Alcoholic and non-alcoholic liver diseases begin from an imbalance in lipid metabolism in hepatocytes as the earliest response. Both liver diseases share common disease features and stages (i.e., steatosis, hepatitis, cirrhosis, and hepatocellular carcinoma). However, the two diseases have differential pathogenesis and clinical symptoms. Studies have elucidated the molecular basis underlying similarities and differences in the pathogenesis of the diseases; the factors contributing to the progression of liver diseases include depletion of sulfhydryl pools, enhanced levels of reactive oxygen and nitrogen intermediates, increased sensitivity of hepatocytes to toxic cytokines, mitochondrial dysfunction, and insulin resistance. Endoplasmic reticulum (ER) stress, which is caused by the accumulation of misfolded proteins and calcium depletion, contributes to the pathogenesis, often causing catastrophic cell death. Several studies have demonstrated a mechanism by which ER stress triggers liver disease progression. Autophagy is an evolutionarily conserved process that regulates organelle turnover and cellular energy balance through decomposing damaged organelles including mitochondria, misfolded proteins, and lipid droplets. Autophagy dysregulation also exacerbates liver diseases. Thus, autophagy-related molecules can be potential therapeutic targets for liver diseases. Since ER stress and autophagy are closely linked to each other, an understanding of the molecules, gene clusters, and networks engaged in these processes would be of help to find new remedies for alcoholic and non-alcoholic liver diseases. In this review, we summarize the recent findings and perspectives in the context of the molecular pathogenesis of the liver diseases.

Background & Aims Hepatic stellate cells (HSCs) have a role in liver fibrosis. Guanine nucleotide-binding α-subunit 12 (Gα 12 ) converges signals from G-protein-coupled receptors whose ligand levels are elevated in the environment during liver fibrosis; however, information is lacking on the effect of Gα 12 on HSC trans -differentiation. This study investigated the expression of Gα 12 in HSCs and the molecular basis of the effects of its expression on liver fibrosis. Methods Gα 12 expression was assessed by immunostaining, and immunoblot analyses of mouse fibrotic liver tissues and primary HSCs. The role of Gα 12 in liver fibrosis was estimated using a toxicant injury mouse model with Gα 12 gene knockout and/or HSC-specific Gα 12 delivery using lentiviral vectors, in addition to primary HSCs and LX-2 cells using microRNA (miR) inhibitors, overexpression vectors, or adenoviruses. miR-16, Gα 12 , and LC3 were also examined in samples from patients with fibrosis. Results Gα 12 was overexpressed in activated HSCs and fibrotic liver, and was colocalised with desmin. In a carbon tetrachloride-induced fibrosis mouse model, Gα 12 ablation prevented increases in fibrosis and liver injury. This effect was attenuated by HSC-specific lentiviral delivery of Gα 12 . Moreover, Gα 12 activation promoted autophagy accompanying c-Jun N-terminal kinase-dependent ATG12-5 conjugation. In addition, miR-16 was found to be a direct inhibitor of the de novo synthesis of Gα 12 . Modulations of miR-16 altered autophagy in HSCs. In a fibrosis animal model or patients with severe fibrosis, miR-16 levels were lower than in their corresponding controls. Consistently, cirrhotic patient liver tissues showed Gα 12 and LC3 upregulation in desmin-positive areas. Conclusions miR-16 dysregulation in HSCs results in Gα 12 overexpression, which activates HSCs by facilitating autophagy through ATG12-5 formation. This suggests that Gα 12 and its regulatory molecules could serve as targets for the amelioration of liver fibrosis. Lay summary Guanine nucleotide-binding α-subunit 12 (Gα 12 ) is upregulated in activated hepatic stellate cells (HSCs) as a consequence of the dysregulation of a specific microRNA that is abundant in HSCs, facilitating the progression of liver fibrosis. This event is mediated by c-Jun N-terminal kinase-dependent ATG12-5 formation and the promotion of autophagy. We suggest that Gα 12 and its associated regulators could serve as new targets in HSCs for the treatment of liver fibrosis.

The clinical benefits of a concomitant mitral valve (MV) surgery in patients with moderate ischemic mitral regurgitation (iMR) undergoing coronary artery bypass grafting (CABG) remain controversial.The study involved 710 patients (mean age, 65.0±8.9 years; 504 males) with moderate iMR undergoing CABG between 1990 and 2015. Of these, 116 (16.3%) patients underwent a concomitant MV surgery (MVS; replacement in 10, repair in 106) and 594 (83.7%) underwent CABG only. Clinical and echocardiographic outcomes were compared before and after adjustment with the use of propensity score (PS) analyses.Early mortality occurred in 22 (3.7%) and 13 (11.2%) patients in CABG-only and CABG with MVS group, respectively (P=0.001). After adjustment, CABG with MVS group showed significantly increased risks of early death (P0.001), low cardiac output syndrome (LCOS) (P=0.001) and surgical bleeding (P=0.014). During a median follow-up of 78.0 months (quartile 1-3, 33.6-115.9 months), overall mortality occurred in 286 (40.3%) patients. The addition of an MV surgery showed an increased risk of overall mortality [hazard ratio (HR), 1.34; 95% confidence interval (CI), 0.99-1.80; P=0.055], which became comparable 1 year after surgery on landmark survival analysis (HR, 0.94; 95% CI, 0.64-1.39; P=0.772). Improved left ventricular (LV) ejection fraction and LV reverse remodeling were observed in both groups without significant intergroup differences.The addition of a concomitant MV surgery increased the risk of early mortality and complications in patients with moderate iMR undergoing CABG. In long-term clinical and echocardiographic outcomes, a concomitant MV surgery seemed to confer no significant clinical benefits.

OBJECTIVES Pericardial effusion can cause haemodynamic compromise after heart transplantation. We identified the effects of soft drains on the development of pericardial effusion. METHODS We enrolled 250 patients ≥17 years of age who underwent heart transplantation between July 1999 and April 2012 and received two conventional tubes (n = 96; 32 French), or two tubes with a soft drain (n = 154; 4.8 mm wide). The development of significant pericardial effusion or the need for drainage procedure during 1 month after heart transplantation was compared with the use of the propensity score matching method to adjust for selection bias. RESULTS At 1 month after transplantation, 69 patients (27.6%) developed significant pericardial effusion. Among these, 13 patients (5.2%) underwent pericardial drainage. According to multivariate analysis, history of previous cardiac surgery [odds ratio (OR) = 0.162; 95% confidence interval (CI) = 0.046-0.565; P = 0.004] and placement of a soft drain (OR = 0.186; 95% CI = 0.100-0.346; P < 0.001) were significant factors that prevented pericardial effusion or the need for drainage during the early postoperative period. For the 82 propensity score matched pairs, patients receiving an additional soft drain were at a lower risk of the development of significant pericardial effusion or the need for a pericardial drainage procedure during 1 month (OR = 0.148; 95% CI = 0.068-0.318; P < 0.001) compared with those receiving only two conventional tubes. CONCLUSIONS Pericardial soft drainage is a simple and safe procedure that reduces pericardial effusion and decreases the need for pericardial drainage after heart transplantation.

Background and objectives We identified the impact of extracorporeal cardiopulmonary resuscitation (ECPR) followed by therapeutic hypothermia on survival and neurologic outcome in patients with prolonged refractory in-hospital cardiac arrest (IHCA). Methods We enrolled 16 adult patients who underwent ECPR followed by therapeutic hypothermia between July 2011 and December 2015, for IHCA. Survival at discharge and cerebral performance category (CPC) scale were evaluated. Results All patients received bystander cardiopulmonary resuscitation (CPR); the mean CPR time was 66.5±29.9 minutes, and the minimum value was 39 minutes. Eight patients (50%) were discharged alive with favorable neurologic outcomes (CPC 1-2). The mean follow-up duration was 20.1±24.3 months, and most deaths occurred within 21 days after ECPR; thereafter, no deaths occurred within one year after the procedure. Conclusion ECPR followed by therapeutic hypothermia could be considered in prolonged refractory IHCA if bystander-initiated conventional CPR is performed.

Background: Although a residual intimal tear may contribute to the dilatation of the descending aorta following surgical repair of acute type I aortic dissection (AD), its causal relationship has not been elucidated by clinical data due to the limited resolution of imaging modalities. Methods: This study enrolled 41 patients (age, 55.2±11.9 years) who were evaluated with dual-source computed tomography (CT) imaging of the whole aorta in the setting of the surgical repair of acute type I AD. Logistic regression models were used to determine the predictors of a composite of the aortic aneurysm formation (diameter ＞55 mm) and rapid aortic expansion (＞5 mm/yr). Results: On initial CT, a distal re-entry tear was identified in 9 patients. Two patients failed to achieve proximal tear exclusion by the surgery. Serial follow-up CT evaluations (median, 24.6 months; range, 6.0 to 67.2 months) revealed that 14 patients showed rapid expansion of the descending aorta or aortic aneurysm formation. A multivariate analysis revealed that the residual intimal tear (odds ratio [OR], 4.31; 95% confidence interval [CI], 1.02 to 19.31) and the patent false lumen in the early postoperative setting (OR, 4.64; 95% CI, 0.99 to 43.61) were predictive of the composite endpoint. Conclusion: The presence of a residual intimal tear following surgery for acute type I AD adversely influenced the expansion of the descending aorta.

Targeted temperature management (TTM) improves survival and neurological outcome after nontraumatic cardiac arrest. However, TTM is not used widely after traumatic cardiac arrest because of concerns that it might exacerbate bleeding. We report the use of postarrest TTM after repair of blunt myocardial rupture. A 48-year-old man was admitted after being rescued from a major traffic accident by the local emergency service. Focused sonography showed pericardial fluid without cardiac tamponade. Computed tomography showed a large hematoma in the anterior mediastinum associated with hemopericardium. The patient developed cardiac arrest during the operative preparations. Repeat bedside sonography revealed a large pericardial effusion and signs of cardiac tamponade. Spontaneous circulation was restored after ultrasound-guided pericardiocentesis. His Glasgow Coma Scale score was 3. The patient was transported promptly to the operating room and underwent median sternotomy without cardiopulmonary bypass. A rupture of the junction of the superior vena cava/right atrium and left atrial appendage was detected and was closed by direct suturing. Immediately after return to the intensive care unit, we performed TTM (target body temperature 34.5°C) using a surface-cooling device at 4 hours postarrest. TTM was maintained for 24 hours and controlled gradual rewarming was then initiated. He regained consciousness 36 hours postrewarming with limited speech ability. The patient recovered with no further cardiac events and was discharged 3 weeks after admission, with no other serious complications. The patient was neurologically intact (cerebral performance category 1) at 6 months of follow-up. This case demonstrates the potential benefit and applicability of postarrest TTM in patients after repair of blunt myocardial rupture.

There are many ways to treat focal hyperhidrosis, including surgeries for palmar and axillary hyperhidrosis. However, doctors and patients tend to be reluctant to perform surgery for plantar hyperhidrosis due to misconceptions and prejudices about surgical treatment. In addition, few studies have reported the outcome of surgeries for plantar hyperhidrosis. Therefore, the objective of this study was to determine the outcome (early and late postoperative satisfaction, complication, compensatory hyperhidrosis, recurrence rate, and efficiency) of surgical treatment for plantar hyperhidrosis.From August 2014 to October 2015, lumbar sympathetic block (LSB) was performed in 82 patients with plantar hyperhidrosis using clipping method. Limited video-assisted LSB was performed using 5 mm ligamax-clip or 3 mm horizontal-clip after identifying L3-4 sympathetic ganglion through finger-touch and endoscopic vision.Of the 82 patients, 45 were male and 37 were female. Their mean age was 26.38 years (range, 14-51 years). Mean follow-up time was 6.60 ± 3.56 months. Mean early postoperative satisfaction score was 9.6 on the 10th day postoperative evaluation. At more than 1 month later, the mean late postoperative satisfaction score was 9.2. There was no significant difference in early postoperative satisfaction score between clipping level L3 and L4/5. However, late postoperative satisfaction score was significantly better in the L3 group than that in the L4/5 group. Patient's age and body mass index did not affect the satisfaction score. However, male patients and patients who had history of hyperhidrosis operation showed higher satisfaction score than others.Limited video-assisted LSB using clip provided good results with minimal complications and low compensatory hidrosis, contrary to the prejudice toward it. Therefore, surgical treatment is recommended for plantar hyperhidrosis.

Extracorporeal cardiopulmonary resuscitation can be used as a rescue strategy in cases of prolonged cardiac arrest caused by massive pulmonary embolism. We present a case of a male patient who was in prolonged cardiac arrest following massive pulmonary embolism. Veno-arterial extracorporeal membrane oxygenation was initiated approximately 93 min after prolonged cardiopulmonary resuscitation. After resuscitation, bedside echocardiography and a chest computed tomography angiogram revealed a massive pulmonary embolism during extracorporeal membrane oxygenation support. The patient received transcatheter mechanical thrombectomy without haemodynamic instability in extracorporeal membrane oxygenation support. He was also treated with therapeutic hypothermia to improve neurological outcome. Renal replacement therapy for acute kidney injury was continued for 36 days. The patient was discharged at 60 days after admission with no serious complications. This case demonstrates that veno-arterial extracorporeal membrane oxygenation and therapeutic hypothermia are an effective treatment strategy for prolonged cardiac arrest caused by massive pulmonary embolism.

This research is concerned with the fungicidal properties of nano-size silver colloidal solution used as an agent for antifungal treatment of various plant pathogens. We used WA-CV-WA13B, WA-AT-WB13R, and WA-PR-WB13R silver nanoparticles (AgNPs) at concentrations of 10, 25, 50, and 100 ppm. Eighteen different plant pathogenic fungi were treated with these AgNPs on potato dextrose agar (PDA), malt extract agar, and corn meal agar plates. We calculated fungal inhibition in order to evaluate the antifungal efficacy of silver nanoparticles against pathogens. The results indicated that AgNPs possess antifungal properties against these plant pathogens at various levels. Treatment with WA-CV-WB13R AgNPs resulted in maximum inhibition of most fungi. Results also showed that the most significant inhibition of plant pathogenic fungi was observed on PDA and 100 ppm of AgNPs.

The triglyceride glucose (TyG) index is a useful surrogate marker for insulin resistance, which is an important risk factor for coronary artery disease (CAD). However, data on the relationship of the TyG index and coronary plaque characteristics are limited. This study included 2840 participants with near-normal renal function who underwent coronary computed tomography angiography. CAD was defined as the presence of any plaques, and obstructive CAD was defined as the presence of plaques with ≥50% stenosis. The relationship between the TyG index and noncalcified plaque (NCP), calcified or mixed plaque (CMP), and coronary artery calcium score (CACS) was evaluated. All participants were stratified into 4 groups based on the quartiles of the TyG index. The prevalence of CAD and obstructive CAD significantly increased with increasing quartiles. The risk for NCP and obstructive NCP was not different among all groups. However, compared with group I (lowest quartile), the risk for CMP was higher in groups III (odds ratio [OR]: 1.438) and IV (highest quartile) (OR: 1.895) (P 400 (OR: 1.448) (P

A Bacillus species that produces 2,3-butanediol (2,3-BD), termed BRC1, was newly isolated, and a 2,3-BD dehydrogenase (Bdh) from this species was identified and characterized at the molecular and biochemical level. Sequence analysis revealed that Bdh is homologous to D-2,3-BD dehydrogenases. An analysis of the enzymatic properties of Bdh overexpressed in Escherichia coli confirmed the molecular results, showing preferred activity toward D-2,3-BD. Optimum pH, temperature, and kinetics determined for reductive and oxidative reactions support the preferential production of 2,3-BD during cell growth. Overexpression of bdh under the control of a xylose-inducible promoter resulted in increased enzyme activity and enhanced 2,3-BD production in Bacillus sp. BRC1. Additionally, a hydrolysate of cellulosic material, (empty palm fruit bunches), was successfully used for the enhanced production of 2,3-BD in the recombinant Bacillus strain.

SummaryWhat is known and objective Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus (MRSA) infection and shows time-dependent bacterial killing. The current study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of vancomycin and explored its optimal dosing regimens by modeling and simulation. Methods Pharmacokinetics study was performed for 20 patients who were treated with vancomycin intravenously, 1000 mg, every 12 h, and blood for PK was randomly drawn within prespecified time windows. PD study was in vitro time-kill experiment for vancomycin against 20 MRSA strains independent of the PK study, where bacterial titre was measured at 0, 2, 4, 8, 24 h after the beginning of vancomycin exposure at 0, 1, 2, 4, 8, 16, 32× minimum inhibitory concentrations. PK and PD models were built from each data set, and simulation for MRSA titre changes over time in human body was performed for various vancomycin dosing regimens using NONMEM®. Results Vancomycin followed a two-compartment PK model, and creatinine clearance was the significant covariate affecting the clearance of vancomycin. PD model described the in vitro time-kill data well. The PK/PD model predicted clear dose–response relationships of vancomycin. The therapeutic dosing regimens of vancomycin, suggested by the simulation studies, showed good agreement with the current clinical practice guidance, which indicates that this PK/PD modeling and simulation approach could prove useful for identifying optimal dosing regimens of other antibiotics and expediting novel antibiotic development. Using PD model from in vitro time-kill study and human PK model from phase 1 study, we could predict whether the drug is going to be efficacious or obtain insight into the optimal dosing regimens for a novel antibiotic agent in the early phases of drug development process.

Although a mobile papillary fibroelastoma in the left ventricle should be excised to prevent systemic embolism, difficulties in surgical exposure of a left ventricular mass are not uncommon. Herein, we report a minimally invasive approach for resecting left ventricular papillary fibroelastoma using thoracoscopic assistance.

Purpose: To assess the midterm results of the hydroxyapatite hip system with acetabular cups, with particular emphasis upon cup wearand loosening, using a computer assisted-3 dimensional technique. Materials and Methods: From March 1992 to December 1996, 52 patients (61 hips) were available for inclusion in this study after an average duration of follow up of 6 years and 4 months. Clinical evaluation was performed using the Harris hip scoring system. Initial postoperative and long term follow up films were digitized, and 2 dimensional linear and 3 dimensional wear was measured by using a computer assisted-3 dimensional technique. Acetabular bone changes are described using previous published methods. Results: An analysis of the clinical results showed a mean Harris hip score of 47.2 points preoperatively and 89.8 points at the final visit. The mean polyethylene 3D-linear wear rate was 0.26 mm/year and mean volumetric wear rate was 105.9 /year. In 16 hips (26.2%) the linear wear rate was more than 0.3 mm/year (0.30-0.74 mm/year). Osteolytic changes of the acetabulum were recorded in 51% around acetabular cups, in which considerable wear of the acetabular polyethylene was evident by the five-year radiographic findings. Conclusion: Midterm results of hydroxyapatite coated acetabular cups were disappointing in terms of acetabular cup and liner wear, despite early accelerated bone remodeling by hydroxyapatite and excellent early clinical results.