Determination of the theoretical personalized optimum chest compression point using anteroposterior chest radiography

Objective There is a traditional assumption that to maximize stroke volume, the point beneath which the left ventricle (LV) is at its maximum diameter (P_max.LV) should be compressed. Thus, we aimed to derive and validate rules to estimate P_max.LV using anteroposterior chest radiography (chest_AP), which is performed for critically ill patients urgently needing determination of their personalized P_max.LV. Methods A retrospective, cross-sectional study was performed with non-cardiac arrest adults who underwent chest_AP within 1 hour of computed tomography (derivation:validation=3:2). On chest_AP, we defined cardiac diameter (CD), distance from right cardiac border to midline (RB), and cardiac height (CH) from the carina to the uppermost point of left hemi-diaphragm. Setting point zero (0, 0) at the midpoint of the xiphisternal joint and designating leftward and upward directions as positive on x- and y-axes, we located P_max.LV (x_max.LV, y_max.LV). The coefficients of the following mathematically inferred rules were sought: x_max.LV=α0*CD-RB; y_max.LV=β0*CH+γ0 (α0: mean of [x_max.LV+RB]/CD; β0, γ0: representative coefficient and constant of linear regression model, respectively). Results Among 360 cases (52.0±18.3 years, 102 females), we derived: x_max.LV=0.643*CD-RB and y_max.LV=55-0.390*CH. This estimated P_max.LV (19±11 mm) was as close as the averaged P_max.LV (19±11 mm, P=0.13) and closer than the three equidistant points representing the current guidelines (67±13, 56±10, and 77±17 mm; all P<0.001) to the reference identified on computed tomography. Thus, our findings were validated. Conclusion Personalized P_max.LV can be estimated using chest_AP. Further studies with actual cardiac arrest victims are needed to verify the safety and effectiveness of the rule

Agaricus blazei Extract Induces Apoptosis through ROS-Dependent JNK Activation Involving the Mitochondrial Pathway and Suppression of Constitutive NF-κB in THP-1 Cells

Agaricus blazei is widely accepted as a traditional medicinal mushroom, and it has been known to exhibit immunostimulatory and anti-cancer activity. However, the apoptotic mechanism in cancer cells is poorly understood. In this study, we have investigated whether A. blazei extract (ABE) exerts antiproliferative and apoptotic effects in human leukemic THP-1 cells. We observed that ABE-induced apoptosis is associated with the mitochondrial pathway, which is mediated by reactive oxygen species (ROS) generation and prolonged c-Jun N-terminal kinase (JNK) activation. In addition, the ABE treatment resulted in the accumulation of cytochrome c in the cytoplasm, an increase in caspase activity, and an upregulation of Bax and Bad. With those results in mind, we found that ABE decreases constitutive NF-κB activation and NF-κB-regulated gene products such as IAP-1 and -2. We concluded that ABE induces apoptosis with ROS-dependent JNK activation and constitutive activated NF-κB inhibition in THP-1 cells

Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries

Background: This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameterduring ergonovine provocation testing.Methods: A total of 158 patients who underwent an ergonovine provocation test with intracoronaryadenosine injection between 2011 and 2014 were selected. Patients were divided into four groups basedon the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1,induced spasm &lt; 50%; Group 2, 50–89%; Group 3, 90–99%; and Group 4, total occlusion.Results: Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ±± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardialartery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3,and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4,respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lowerin patients with spasm positive results (0.68 [0.59–0.76] vs. 0.18 [0.00–0.41], p &lt; 0.001 in the studypopulation; 0.60 [0.54–0.67] vs. 0.40 [0.27–0.44], p &lt; 0.001 in Group 2) with the best cut-off value of0.505 (sensitivity 0.955, specificity 0.921).Conclusions: Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstrictedepicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter wassignificantly lower in patients with spasm positive results

Vibrio cholerae non-O1,non-O139 Isolated from Pleural Effusion Following Total Gastrectomy

We isolated non-O1, non-O139 Vibrio cholerae from pleural effusion in a patient with recurred advanced gastric caner after total gastrectomy. We also recovered the organism from the patient's stool culture. The patient did not experience gastrointestinal symptoms such as diarrhea except heartburn and epigastric discomfort from stomach cancer before admission. The suspected route of infection is directly from the gastrointestinal tract through the previous surgical wounds. After antibiotic treatment, no more V. cholerae was isolated and the patient was well discharged from the hospital. This is the first report of V. cholerae infection associated with pleural effusion in a long-term latent carrier of the organism

A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model

Introduction : Tumor cell interactions with the microenvironment, especially those of bone-marrow-derived myeloid cells, are important in various aspects of tumor metastasis. Myeloid-derived suppressor cells (MDSCs) have been suggested to constitute tumor-favoring microenvironments. In this study, we elucidated a novel mechanism by which the MDSCs can mediate spontaneous distant metastasis of breast cancer cells. Methods : Murine breast cancer cells, 4T1 and EMT6, were orthotopically grafted into the mammary fat pads of syngeneic BALB/c mice. CD11b+Gr-1+ MDSCs in the spleen, liver, lung and primary tumor mass were analyzed. To evaluate the role of MDSCs in the distant metastasis, MDSCs were depleted or reconstituted in tumor-bearing mice. To evaluate whether MDSCs in the metastasizing tumor microenvironment affect breast cancer cell behavior, MDSCs and cancer cells were co-cultivated. To investigate the role of MDSCs in in vivo metastasis, we blocked the interactions between MDSCs and cancer cells. Results : Using a murine breast cancer cell model, we showed that murine breast cancer cells with high IL-6 expression recruited more MDSCs and that the metastasizing capacity of cancer cells paralleled MDSC recruitment in tumor-bearing mice. Metastasizing, but not non-metastasizing, tumor-derived factors induced MDSCs to increase IL-6 production and full activation of recruited MDSCs occurred in the primary tumor site and metastatic organ in the vicinity of metastasizing cancer cells, but not in lymphoid organs. In addition, tumor-expanded MDSCs expressed Adam-family proteases, which facilitated shedding of IL-6 receptor, thereby contributing to breast cancer cell invasiveness and distant metastasis through IL-6 trans-signaling. The critical role of IL-6 trans-signaling was confirmed in both the afferent and efferent pathways of metastasis. Conclusion : In this study, we showed that metastasizing cancer cells induced higher MDSCs infiltration and prompted them to secret exaggerated IL-6 as well as soluble IL-6Rα, which, in turn, triggered a persistent increase of pSTAT3 in tumor cells. This potential tumor-MDSC axis involving IL-6 trans-signaling directly affected breast cancer cell aggressiveness, leading to spontaneous metastasis.This work was supported by grants from the National R&D Program for Cancer Control, Ministry of Health & Welfare (12202001), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012008122), and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012014152).Peer Reviewe

Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.

BackgroundDiabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.PurposeWe hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.MethodsRat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.ResultsQuantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.ConclusionTwo isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP

Predictive and protective role of high-density lipoprotein cholesterol in acute myocardial infarction

Background: It is unclear whether high-density lipoprotein cholesterol (HDL-C) level predicts cardiovascular events and has a protective effect in patients with acute myocardial infarction (AMI) undergo- ing percutaneous coronary intervention (PCI) and statin treatment. Methods: A total of 15,290 AMI patients receiving statins were selected from the Korean Myocardial Infarction Registry. Baseline HDL-C level was used to identify patients with low (group A), normal (group B), and high (group C) HDL-C levels according to the Adult Treatment Panel III criteria. Clinical outcomes were compared in propensity-adjusted and matched cohorts. The primary endpoint was a composite of cardiovascular death and recurrent myocardial infarction.  Results: At the median follow-up of 11.5 months, the primary endpoint occurred in 2.7% (112/4098), 1.4% (54/3910), and 1.2% (8/661) of patients in groups A, B, and C, respectively. In the propensity- -adjusted cohort, low HDL-C level increased the risk of primary endpoint (hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.274–2.417, p = 0.001), whereas high HDL-C level did not reduce this risk (HR 0.562, 95% CI 0.275–1.146, p = 0.113). In the propensity-matched cohort, low HDL-C level increased the risk of primary endpoint (HR 1.716, 95% CI 1.210–2.434, p = 0.002), whereas high HDL-C level reduced this risk (HR 0.449, 95% CI 0.214–0.946, p = 0.035).  Conclusions: In AMI patients treated with PCI and statins, low HDL-C level increases the risk of cardiovascular death and recurrent myocardial infarction, whereas high HDL-C level likely reduces the risk of cardiovascular events, especially for ST-elevation myocardial infarction.

Psychometric Properties of the Hypomania Checklist-32 in Korean Patients with Mood Disorders

OBJECTIVE The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS The KHCL-32-R2 showed a three-factorial structure (eigenvalue ＞2) that accounted for 43.26% of the total variance. Factor 1 was labeled "active/elated" and included 16 items; factor 2, "irritable/distractible" and included 9 items; and factor 3 was labeled "risk-taking/indulging" and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach's alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery- Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were -0.66 (p=0.41), -0.14 (p=0.9), and 0.61 (p＜0.001), respectively. CONCLUSION The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings

Airway epithelial cells initiate the allergen response through transglutaminase 2 by inducing IL-33 expression and a subsequent Th2 response

Transglutaminase 2 (TG2) is a post-translational protein-modifying enzyme that catalyzes the transamidation reaction, producing crosslinked or polyaminated proteins. Increased TG2 expression and activity have been reported in various inflammatory conditions, such as rheumatoid arthritis, inflammation-associated pulmonary fibrosis, and autoimmune encephalitis. In particular, TG2 from epithelial cells is important during the initial inflammatory response in the lung. In this study, we evaluated the role of TG2 in the pathogenesis of allergic asthma, particularly whether TG2 affects initial activation signaling leading to Th2 differentiation against antigens. Methods We induced allergic asthma by ovalbumin sensitization and intranasal challenge in wild-type (WT) BALB/c and TG2-deficient mice. Broncheoalveolar lavage fluid cells and intracellular cytokine production were analyzed by flow cytometry. Interleukin (IL)-33 and TG2 expression in lung epithelial cells was detected by confocal microscopy. Results Airway responsiveness was attenuated in TG2-deficient mice compared to that in the WT control. In addition, recruitment of eosinophils and Th2 and Th17 differentiation decreased in TG2-deficient mice. Treatment with cysteamine, a transglutaminase inhibitor, also reduced airway hypersensitivity, inflammatory cell recruitment, and T helper cell differentiation. TG2-deficient mice showed reduced IL-33 expression following induction of allergic asthma compared to those in the WT control. Conclusions We found that pulmonary epithelial cells damaged by allergens triggered TG2-mediated IL-33 expression leading to type 2 responses by recruiting both innate and adaptive arms of the immune system.Peer Reviewe