Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients.

INTRODUCTION: The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects. METHODS AND ANALYSIS: In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint. ETHICS AND DISSEMINATION: The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. TRIAL REGISTRATION NUMBER: UMIN000045229.

Extremely Tough, Stretchable Gel Electrolytes with Strong Interpolymer Hydrogen Bonding Prepared Using Concentrated Electrolytes to Stabilize Lithium-Metal Anodes.

Extremely tough and stretchable gel electrolytes, which can be prepared by leveraging the strong interpolymer hydrogen bonding in concentrated lithium (Li)-salt electrolytes, are reported. These electrolytes can be realized by optimizing the competitive hydrogen-bonding interactions between polymer chains, solvent molecules, Li cations, and counteranions. Free polar solvent molecules, which typically impede interpolymer hydrogen bonding, are scarce in concentrated electrolytes; this feature can be exploited to prepare hydrogen-bonded gel electrolytes with unprecedented toughness. In contrast, free solvent molecules are abundant in electrolytes with typical concentrations, yielding considerably weaker gel electrolytes. The tough gel electrolyte can be used an artificial protective layer for Li-metal anodes, as it considerably enhances the cycling stability of a Li symmetric cell through uniform Li deposition/dissolution. Additionally, employing the gel electrolyte as the protecting layer significantly improves the cycling performance of the Li||LiNi0.6 Co0.2 Mn0.2 O2 full cell.

Phenotyping of Elderly Patients With Heart Failure Focused on Noncardiac Conditions: A Latent Class Analysis From a Multicenter Registry of Patients Hospitalized With Heart Failure.

Background The burden of noncardiovascular conditions is becoming increasingly prevalent in patients with heart failure (HF). We aimed to identify novel phenogroups incorporating noncardiovascular conditions to facilitate understanding and risk stratification in elderly patients with HF. Methods and Results Data from a total of 1881 (61.2%) patients aged ≥65 years were extracted from a prospective multicenter registry of patients hospitalized for acute HF (N=3072). We constructed subgroups of patients with HF with preserved ejection fraction (HFpEF; N=826, 43.9%) and those with non-HFpEF (N=1055, 56.1%). Latent class analysis was performed in each subgroup using 17 variables focused on noncardiovascular conditions (including comorbidities, Clinical Frailty Scale, and Geriatric Nutritional Risk Index). The latent class analysis revealed 3 distinct clinical phenogroups in both HFpEF and non-HFpEF subgroups: (1) robust physical and nutritional status (Group 1: HFpEF, 41.2%; non-HFpEF, 46.0%); (2) multimorbid patients with renal impairment (Group 2: HFpEF, 40.8%; non-HFpEF, 41.9%); and (3) malnourished patients (Group 3: HFpEF, 18.0%; non-HFpEF, 12.1%). After multivariable adjustment, compared with Group 1, patients in Groups 2 and 3 had a higher risk for all-cause death over the 1-year postdischarge period (hazard ratio [HR], 2.79 [95% CI, 1.64-4.81] and HR, 2.73 [95% CI, 1.39-5.35] in HFpEF; HR, 1.96 [95% CI, 1.22-3.14] and HR, 2.97 [95% CI, 1.64-5.38] in non-HFpEF; respectively). Conclusions In elderly patients with HF, the phenomapping focused on incorporating noncardiovascular conditions identified 3 phenogroups, each representing distinct clinical outcomes, and the discrimination pattern was similar for both patients with HFpEF and non-HFpEF. This classification provides novel risk stratification and may aid in clinical decision making.

Characterization of Electrodeposited Li Metal by Cryo-Scanning Transmission Electron Microscopy/Electron Energy Loss Spectroscopy.

The Li metal anode is a promising key component for next-generation high-energy-density batteries. Understanding the charge/discharge mechanism of Li metal is therefore necessary for the effective utilization of Li metal anodes in commercial batteries. In this study, scanning transmission electron microscopy (STEM) combined with electron energy loss spectroscopy (EELS) was conducted to reveal the chemical state of the Li metal anode surface. Cryogenic techniques and ultramicroelectrodes (UMEs) enabled the observation of electrodeposited Li metal on the nanometer scale. The chemical compositions of several surface layers were revealed by cryo-STEM-EELS analysis, and these measurements gave crucial information regarding the surface layer of the electrodeposited Li metal.

Lithiation/Delithiation Properties of Lithium Silicide Electrodes in Ionic-Liquid Electrolytes.

We investigated the impact of electrolyte difference on lithiation and delithiation properties of a Li1.00Si electrode to improve the Coulombic efficiency (CE) of Si-based electrodes. The results of X-ray diffraction, Raman spectroscopy, and soft X-ray emission spectroscopy demonstrated that a portion of the Li in Li1.00Si desorbed by simply immersing the electrode in an ionic-liquid electrolyte, that is, the phase transition of Li1.00Si to Si occurred. In contrast, this phenomenon was not confirmed in an organic-liquid electrolyte. Instead, the desorbed Li was consumed for the formation of a surface film; thus, the Li in Li1.00Si did not elute into the electrolyte. The addition of vinylene carbonate (VC) to the ionic-liquid electrolyte suppressed the phase transition of Li1.00Si to Si. Although the Li1.00Si electrode showed a low initial CE and poor cycling performance in a VC-free electrolyte, the electrode exhibited a high CE and a remarkable cycle life in the VC-added electrolyte. It was considered that no desorption of the mechanically added Li in Li1.00Si contributed to the superior cycle life; thus, the characteristic ductility, malleability, and high electrical conductivity of lithium silicide should improve the electrochemical performance.

Reaction Behavior of a Silicide Electrode with Lithium in an Ionic-Liquid Electrolyte.

Silicides are attractive novel active materials for use in the negative-electrodes of next-generation lithium-ion batteries that use certain ionic-liquid electrolytes; however, the reaction mechanism of the above combination is yet to be clarified. Possible reactions at the silicide electrode are as follows: deposition and dissolution of Li metal on the electrode, lithiation and delithiation of Si, which would result from the phase separation of the silicide, and alloying and dealloying of the silicide with Li. Herein, we examined these possibilities using various analysis methods. The results revealed that the lithiation and delithiation of silicide occurred.

Asymmetry in the Solvation-Desolvation Resistance for Li Metal Batteries.

Li metal electrode is the ultimate choice use in Li ion batteries as high-energy storage systems. An obstacle to its practical realization is Li dendrite formation. In this study, the desolvation resistance of the Li metal electrode, which is strongly related to the inhibition of Li dendrite formation, is investigated. By applying a Laplace transform impedance technique, the desolvation/solvation resistances were successfully separated and analyzed in cells using liquid electrolytes containing different lithium salts, revealing asymmetry in the desolvation/solvation resistances of Li metal electrodes. The desolvation resistances, which supposedly require large amounts of energy derived from the strong interaction between Li+ ion and solvents, were smaller than the solvation resistances. It has also been revealed that the larger resistance in the desolvation process is effective for suppressing Li dendrite formation further.

Novel physiological insight into a lotus root appearance in stable coronary artery diseases; Report of two cases.

So far physiological significance of multiple intraluminal channels separated by thin wall structures, so called "a lotus root appearance", in an angiographic insignificant lesion in patients with suspected angina pectoris has remained undetermined. Here we present two cases that showed a "reverse visual-functional mismatch" phenomenon of a lotus root appearance using the indexes of myocardial fractional flow reserve and/or coronary flow velocity reserve. Our findings may provide a novel physiological insight into a lotus root appearance as a high possibility of critical functional stenosis in those with stable coronary artery diseases.

Feasibility study of automated framework for estimating lung tumor locations for target-based patient positioning in stereotactic body radiotherapy.

OBJECTIVE: To investigate the feasibility of an automated framework for estimating the lung tumor locations for tumor-based patient positioning with megavolt-cone-beam computed tomography (MV-CBCT) during stereotactic body radiotherapy (SBRT). METHODS: A lung screening phantom and ten lung cancer cases with solid lung tumors, who were treated with SBRT, were employed to this study. The locations of tumors in MV-CBCT images were estimated using a tumor-template matching technique between a tumor template and the MV-CBCT. Tumor templates were produced by cropping the gross tumor volume (GTV) regions, which were enhanced by a Sobel filter or a blob structure enhancement (BSE) filter. Reference tumor locations (grand truth) were determined based on a consensus between a radiation oncologist and a medical physicist. RESULTS: According to the results of the phantom study, the average Euclidean distances of the location errors in the original, Sobel-filtered, and BSE-filtered images were 2.0 ± 4.1 mm, 12.8 ± 9.4 mm, and 0.4 ± 0.5 mm, respectively. For clinical cases, these were 3.4 ± 7.1 mm, 7.2 ± 11.6 mm, and 1.6 ± 1.2 mm, respectively. CONCLUSION: The feasibility study suggests that our proposed framework based on the BSE filter may be a useful tool for tumor-based patient positioning in SBRT.

Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: a systematic review.

QUESTION: What are typical values of physical function for women diagnosed with breast cancer and how do these compare to normative data? DESIGN: Systematic review with meta-analysis. PARTICIPANTS: Women diagnosed with breast cancer who were before, during or after treatment. OUTCOME MEASURES: Physical function was divided into three categories: aerobic capacity, upper and lower extremity muscular fitness, and mobility. Measures of aerobic capacity included field tests (6-minute walk test, 12-minute walk tests, Rockport 1-mile test, and 2-km walk time) and submaximal/maximal exercise tests on a treadmill or cycle ergometer. Measures of upper and lower extremity muscular fitness included grip strength, one repetition maximum (bench, chest or leg press), muscle endurance tests, and chair stands. The only measure of mobility was the Timed Up and Go test. RESULTS: Of the 1978 studies identified, 85 were eligible for inclusion. Wide ranges of values were reported, reflecting the range of ages, disease severity, treatment type and time since treatment of participants. Aerobic fitness values were generally below average, although 6-minute walk time was closer to population norms. Upper and lower extremity strength was lower than population norms for women who were currently receiving cancer treatment. Lower extremity strength was above population norms for women who had completed treatment. CONCLUSION: Aerobic capacity and upper extremity strength in women diagnosed with breast cancer are generally lower than population norms. Assessment of values for lower extremity strength is less conclusive. As more research is published, expected values for sub-groups by age, treatment, and co-morbidities should be developed. [Neil-Sztramko SE, Kirkham AA, Hung SH, Niksirat N, Nishikawa K Campbell KL (2014) Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: a systematic review.Journal of Physiotherapy60: 189-200].

Changes of cerebral oxygen metabolism and hemodynamics during ECPR with hypothermia measured by near-infrared spectroscopy: a pilot study.

BACKGROUND: The 2010 CPR Guidelines recommend that extracorporeal cardiopulmonary resuscitation (ECPR) using an emergency cardiopulmonary bypass (CPB) should be considered for patients with cardiac arrest. However, it is not yet clear whether this therapy can improve cerebral circulation and oxygenation in these patients. To clarify this issue, we evaluated changes of cerebral blood oxygenation (CBO) during ECPR using near-infrared spectroscopy (NIRS). METHODS: We employed NIRS to measure CBO in the bilateral frontal lobe in patients transported to the emergency room (ER) after out-of-hospital cardiac arrest between November 2009 and June 2011. RESULTS: Fifteen patients met the above criteria. The tissue oxygenation index (TOI) on arrival at the ER was 36.5 %. This increased to 67.8 % during ECPR (P < 0.001). The one patient whose TOI subsequently decreased had a favorable neurological outcome. CONCLUSION: Increase of TOI during ECPR might reflect an improvement in cerebral blood flow, while decrease of TOI after ECPR might reflect oxygen utilization by the brain tissue as a result of neuronal cell survival. NIRS may be useful for monitoring cerebral hemodynamics and oxygen metabolism during CPR.

T1ρ is superior to T2 mapping for the evaluation of articular cartilage denaturalization with osteoarthritis: radiological-pathological correlation after total knee arthroplasty.

PURPOSE: We compared the diagnostic performance of T1ρ and T2 mappings in the evaluation of denatured articular cartilage with osteoarthritis of the knee. MATERIALS AND METHODS: 2D-Sagittal T1ρ and T2 mappings of the knee were obtained from 16 patients before total knee arthroplasty. After surgery, specimens of the femur and tibia were regionally segmented according to a 5-point scale of the severity of denaturalization. The T1ρ and T2 values in the full thickness of the articular cartilage in each region were measured by two observers. The two mappings were compared for their ability to differentiate between normal and denatured articular cartilage and also for their usefulness in grading the severity of the denaturalization using the area under receiver operating characteristic curves (Az). A p<0.05 was considered significant for each analysis. RESULTS: The T1ρ mapping showed a significantly higher Az value than the T2 mapping for the differentiation between normal and denatured articular cartilage (p<0.05). Regarding the assessment of the severity of denaturalization, T1ρ mapping could differentiate between normal and mild denaturalization (p<0.05), but T2 mapping could not. However, there were no significant differences between the two mappings in the discrimination of mild versus moderate denaturalization or of moderate versus severe denaturalization. The two observers showed good agreement in the results (intraclass correlation coefficient=0.81 for T1ρ and 0.92 for T2). CONCLUSION: T1ρ mapping is superior to T2 mapping for the evaluation of denatured articular cartilage with osteoarthritis of the knee.

Synovial sarcoma arising in the vulva cytogenetically confirmed by SYT break-apart rearrangement fluorescence in situ hybridization: A case report and discussion of diagnostic methods.

Synovial sarcoma (SS) is a soft tissue sarcoma of unknown histogenesis that rarely occurs in the female genital tract. We report a case of SS occurring in the right vulva of a young Japanese female. The tumor was composed of poorly differentiated rounded cell areas, surrounded by fibroblastic spindle-shaped cell areas. Immunohistochemically, the tumor cells were focally positive for cytokeratin, vimentin, CD99, Bcl-2 and neuron-specific enolase. The tumor was suspected, but was difficult to confirm as it was an SS based solely on light-microscopic and immunohistochemical findings. Although reverse transcription polymerase chain reaction (RT-PCR) failed to detect SS-specific SYT-SSX fusion gene transcripts using an RNA sample extracted from the formalin-fixed paraffin-embedded tumor tissue, SYT break-apart rearrangement fluorescence in situ hybridization (SYT bar-FISH) successfully confirmed our diagnosis of SS for the tumor. Thus, SYT bar-FISH may be more suitable for the purpose of the molecular diagnosis of SS than conventional RT-PCR when using archival formalin-fixed paraffin-embedded tissue specimens.

Acute cardiac impairment associated with concurrent chemoradiotherapy for esophageal cancer: magnetic resonance evaluation.

PURPOSE: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. METHODS AND MATERIALS: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean ± SE. RESULTS: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% ± 2.98% vs. 59.8% ± 2.56% vs. 60.6% ± 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 ± 2.93 vs. 57.0 ± 3.23 mL/m(2)), LV stroke volume index (38.6 ± 1.56 vs. 29.9 ± 1.60 mL/m(2)), and LV ejection fraction (56.9% ± 1.79% vs. 52.8% ± 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 ± 3.05 vs. 72.4 ± 4.04 vs. 85.4 ± 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 ± 0.54 vs. 4.78 ± 0.43 vs. 4.79 ± 0.50 mm), 9 (6.88 ± 0.45 vs. 5.04 ± 0.38 vs. 5.27 ± 0.47 mm), and 10 (9.22 ± 0.48 vs. 8.08 ± 0.34 vs. 8.19 ± 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference (p < 0.05) after CCRT between the groups. CONCLUSIONS: Concurrent chemoradiotherapy for esophageal cancer impairs LVF from an early treatment stage. This impairment is prominent in patients with high LV dose.

Human proprioceptive adaptations during states of height-induced fear and anxiety.

Clinical and experimental research has demonstrated that the emotional experience of fear and anxiety impairs postural stability in humans. The current study investigated whether changes in fear and anxiety can also modulate spinal stretch reflexes and the gain of afferent inputs to the primary somatosensory cortex. To do so, two separate experiments were performed on two separate groups of participants while they stood under conditions of low and high postural threat. In experiment 1, the proprioceptive system was probed using phasic mechanical stimulation of the Achilles tendon while simultaneously recording the ensuing tendon reflexes in the soleus muscle and cortical-evoked potentials over the somatosensory cortex during low and high threat conditions. In experiment 2, phasic electrical stimulation of the tibial nerve was used to examine the effect of postural threat on somatosensory evoked potentials. Results from experiment 1 demonstrated that soleus tendon reflex excitability was facilitated during states of height-induced fear and anxiety while the magnitude of the tendon-tap-evoked cortical potential was not significantly different between threat conditions. Results from experiment 2 demonstrated that the amplitudes of somatosensory-evoked potentials were also unchanged between threat conditions. The results support the hypothesis that muscle spindle sensitivity in the triceps surae muscles may be facilitated when humans stand under conditions of elevated postural threat, although the presumed increase in spindle sensitivity does not result in higher afferent feedback gain at the level of the somatosensory cortex.

Pretreatment apparent diffusion coefficient of the primary lesion correlates with local failure in head-and-neck cancer treated with chemoradiotherapy or radiotherapy.

PURPOSE: This study was performed to evaluate whether the apparent diffusion coefficient (ADC) of a primary lesion correlates with local failure in primary head-and-neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy or radiotherapy. METHODS AND MATERIALS: We retrospectively studied 38 patients with primary HNSCC (12 oropharynx, 20 hypopharynx, 4 larynx, 2 oral cavity) treated with chemoradiotherapy or radiotherapy with radiation dose to gross tumor volume equal to or over 60 Gy and who underwent pretreatment magnetic resonance imaging, including diffusion-weighted imaging. Ten patients developed local failure during follow-up periods of 2.0 to 9.3 months, and the remaining 28 showed local control during follow-up periods of 10.5 to 31.7 months. The variables that could affect local failure (age, tumor volume, ADC, T stage, N stage, dose, treatment method, tumor location, and overall treatment time) were analyzed using logistic regression analyses for all 38 patients and for 17 patients with Stage T3 or T4 disease. RESULTS: In univariate logistic analysis for all 38 cases, tumor volume, ADC, T stage, and treatment method showed significant (p < 0.05) associations with local failure. In multivariate analysis, ADC and T stage revealed significance (p < 0.01). In univariate logistic analysis for the 17 patients with Stage T3 or T4 disease, ADC and dose showed significant (p < 0.01) associations with local failure. In multivariate analysis, ADC alone showed significance (p < 0.05). CONCLUSIONS: The results suggest that pretreatment ADC, along with T stage, is a potential indicator of local failure in HNSCC treated with chemoradiotherapy or radiotherapy.

A simplified method of T(1)ρ mapping in clinical assessment of knee joint.

PURPOSE: we assessed the clinical utility of our proposed simplified method for T(1)ρ mapping calculations. MATERIALS AND METHODS: ten healthy subjects underwent scanning on a 3-tesla magnetic resonance system using an 8-channel phased-array coil. For each subject, we obtained sagittal T(1)ρ-prepared images using 5 different time of spin-lock pulses (TSL=1, 20, 40, 60, and 80 ms), produced conventional T(1)ρ maps (cT(1)ρ maps) using all TSLs, and recomputed our proposed simplified T(1)ρ maps (sT(1)ρ maps) using a decreasing number of TSLs (from 4 to 2). We then investigated the differences and correlations in T(1)ρ values of the tissues obtained using different numbers of spin-lock times. RESULTS: there was a strong positive correlation (single measure intraclass correlation coefficient=0.948; 95% confidence interval=0.911 to 0.970) in T(1)ρ values of tissues between the cT(1)ρ and sT(1)ρ [1, 80] maps. The 2 maps were comparable, though there was a small difference in T(1)ρ value between the two. The total scan time to acquire the data from 5 spin-lock times was 16 min 15 s. Similarity of the T(1)ρ [1, 80] map with the conventional approach reduced scan time by 60%, to 6 min 30 s. CONCLUSION: the clinical relevance of our proposed simplified method is potentially similar to that of the conventional method, and our method requires a shorter examination time and generally preserves the reliability of the T(1)ρ relaxation time of the tissues.

Joint position affects muscle proton diffusion: Evaluation with a 3-T MR system.

OBJECTIVE: To determine whether joint position affects muscle proton diffusion, fractional anisotropy and primary (lambda(1)), secondary (lambda(2)), and tertiary (lambda(3)) eigenvalues of calf muscles were compared among ankle positions of plantar flexion, intermediate, and dorsiflexion. CONCLUSION: In tibialis anterior, fractional anisotropy and lambda(1) decreased, but lambda(2) and lambda(3) increased (p < 0.01) as the joint angle increased. Opposite results were obtained for the gastrocnemius and soleus (p < 0.05). These results indicate that joint position affects muscle proton diffusion.

Early induction of hypothermia during cardiac arrest improves neurological outcomes in patients with out-of-hospital cardiac arrest who undergo emergency cardiopulmonary bypass and percutaneous coronary intervention.

BACKGROUND: Therapeutic hypothermia for comatose survivors of out-of-hospital cardiac arrest has demonstrated neurological benefits. Although early cooling during cardiac arrest enhances efficacy in animal studies, few clinical studies are available. METHODS AND RESULTS: The 171 patients who failed to respond to conventional cardiopulmonary resuscitation were studied prospectively. Patients underwent emergency cardiopulmonary bypass (CPB) plus intra-aortic balloon pumping, with subsequent percutaneous coronary intervention (PCI) if needed. Mild hypothermia (34 degrees C for 3 days) was induced during cardiac arrest or after return of spontaneous circulation. Of the 171 patients, 21 (12.3%) had a favorable neurological outcome at hospital discharge. An unadjusted rate of favorable outcome decreased in a stepwise fashion for increasing quartiles of collapse-to-34 degrees C interval (P=0.016). An adjusted odds ratio for favorable outcome after collapse-to-CPB interval was 0.89 (95% confidence interval (CI) 0.82-0.97) and after CPB-to-34 degrees C interval, 0.99 (95%CI 0.98-0.99) when collapse-to-34 degrees C interval was divided into 2 components. Favorable neurological accuracy of a collapse-to-CPB interval at a cutoff of 55.5 min and CPB-to-34 degrees C interval at a cutoff of 21.5 min was 85.4% and 89.5%, respectively. CONCLUSIONS: Early attainment of a core temperature had neurological benefits for patients with out-of-hospital cardiac arrest who underwent CPB and PCI. (Circ J 2010; 74: 77 - 85).

Cysteine-rich protein 61 suppresses cell invasion via down-regulation of matrix metalloproteinase-7 expression in the human gastric carcinoma cell line MKN-45.

Cysteine-rich protein 61 (CYR61) is a member of the CCN (CYR61/CTGF/NOV) family, which is associated with progression in a variety of human cancers. Our previous study confirmed that the expression levels of CYR61 protein were decreased in gastric carcinoma compared to non-tumoral mucosa as determined by proteome analysis. Histological research also showed that the reduction in CYR61 expression was significantly correlated with cellular invasiveness and inversely correlated with matrix metalloproteinase-7 (MMP-7/matrilysin) expression in human gastric carcinoma. We examined the cause of CYR61 down-regulation in a human gastric carcinoma cell line, MKN-45. Lower expression of CYR61, but no genetic or epigenetic alterations of the gene, were observed. We then examined the correlation between CYR61 protein and MMP-7 expression and cellular invasiveness in MKN-45 cells. CYR61 was secreted from CYR61 expression-vector-transfected 293T cells, and the supernatant was added to MKN-45 cells. The expression level of MMP-7 was reduced by treatment of the supernatant, including CYR61, in a dose-dependent manner. An invasion assay showed that the cellular invasiveness of MKN-45 was significantly suppressed by the transfection of CYR61 expression vector compared to transfection with a control vector. Taken together, these results raise the possibility that CYR61 suppresses cell invasion at least partly via the down-regulation of MMP-7 expression in human gastric carcinoma cells.