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Background: It remains unclear whether P2Y 12 monotherapy, especially clopidogrel, following short-duration dual antiplatelet therapy (DAPT) is associated with favorable outcomes in patients undergoing complex percutaneous coronary intervention (PCI). Therefore, this study analyzed the efficacy and safety of P2Y 12 inhibitor monotherapy, mostly clopidogrel (78%), in complex PCI following short-term DAPT. Methods: The post-hoc analysis of the SMART-CHOICE trial involving 2,993 patients included 498 cases of complex PCIs, defined by at least one of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with ≥ 2 stents implanted, and a total stent length of ≥ 60 mm. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, and stroke. The primary safety endpoint included bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2 to 5. Results: Complex PCI group had a higher risk of MACCE (4.0% vs. 2.3%, hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.05–2.89, p = 0.033) and a similar risk of BARC types 2–5 bleeding (2.6% vs. 2.6%, HR = 1.02, 95% CI: 0.56–1.86, p = 0.939) compared with those without complex PCIs. Patients undergoing complex PCIs, followed by P2Y 12 inhibitor monotherapy and 12 months of DAPT exhibited similar rates of MACCE (3.8% vs. 4.2%, HR = 0.92, 95% CI: 0.38–2.21, p = 0.853). Conclusions: P2Y 12 inhibitor monotherapy, mostly clopidogrel, following 3 months of DAPT did not increase ischemic events in patients with complex PCIs.

Clinical implications of systemic atherosclerosis in patients with cardiogenic shock (CS) remain unclear. This study investigated the association between polyvascular disease (PVD) and clinical outcome in CS patients.A total of 1247 CS patients was enrolled from the RESCUE registry, a multicenter, observational cohort between January 2014 and December 2018. They were divided into two groups according to presence of PVD, defined as ≥2 coexistence of coronary artery disease, peripheral arterial disease, or cerebrovascular disease. Primary outcome was all-cause death during 12 months of follow-up.136 (10.9%) patients were diagnosed with PVD. The risk of 12-month all-cause death was significantly higher in the PVD group than in the non-PVD group (54.4% versus 40.4%, adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.02-1.69, p = 0.034). There was a significant interaction between PVD and vasoactive inotropic score (VIS) (p for interaction = 0.014). Among the 945 patients with VIS84, PVD was associated with a higher risk of 12-month all-cause death (unadjusted HR 1.77, 95% CI 1.30-2.41, p = 0.030); among the 302 patients with VIS ≥84, the incidence of 12-month all-cause death was similar between the PVD and non-PVD groups (unadjusted HR 1.03, 95% CI 0.68-1.56, p = 0.301).Presence of PVD was associated with 12-month all-cause mortality in patients with CS, especially for less severe forms of CS patients with VIS84. Clinicaltrials.govnumber:NCT02985008.

Controversy remains regarding the optimal antiplatelet regimen in patients with acute coronary syndrome (ACS). This study sought to investigate the efficacy and safety of P2Y12 inhibitor monotherapy compared with conventional dual antiplatelet therapy (DAPT) and aspirin monotherapy in patients with ACS undergoing percutaneous coronary intervention. Data on 4,453 patients were pooled from SMART-DATE and SMART-CHOICE randomized trials. Antiplatelet therapy regimens were categorized as P2Y12 inhibitor monotherapy (P2Y12 inhibitor monotherapy after 3-month DAPT), conventional DAPT (12-month or longer DAPT), and aspirin monotherapy (aspirin monotherapy after 6-month DAPT). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE, a composite of all-cause death, myocardial infarction, and stroke). Inverse-probability of treatment-weighted (IPTW) analysis was performed. At 1 year, patients in the P2Y12 inhibitor monotherapy had a comparable risk of MACCE compared with those in the conventional DAPT (IPTW-adjusted hazard ratio [HR], 0.655; 95% confidence interval [CI] 0.393 to 1.094; p = 0.106), and tended to have a lower risk of MACCE than those in the aspirin monotherapy (IPTW-adjusted HR, 0.606; 95% CI, 0.347 to 1.058; p = 0.078). The adjusted hazard for the Bleeding Academic Research Consortium (BARC) type 2 to 5 bleeding was significantly lower in P2Y12 inhibitor monotherapy than in conventional DAPT (IPTW-adjusted HR, 0.341; 95% CI, 0.190 to 0.614; p0.001) and in aspirin monotherapy (IPTW-adjusted HR, 0.359; 95% CI, 0.182 to 0.708; p = 0.003). In conclusion, among patients with ACS undergoing PCI, P2Y12 inhibitor monotherapy after 3-month DAPT reduced risk of bleeding compared with conventional DAPT and aspirin monotherapy after 6-month DAPT without increasing MACCE.

ObjectiveTo compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI).MethodsThe Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure.ResultsAmong 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2– 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03).ConclusionsCompared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI.Trial registration numberNCT02079194.

In developed countries, global-scale training centers are installed to reflect various regional factors, provide practical education and training, and present comprehensive homeland security management plans. Each local firefighting school, including the central firefighting school in Korea, has various training grounds where firefighters receive education and training. However, the recording and storing of information regarding the air respirator used by the crew during this training is not maintained, nor is information on the remaining air respiratory system at the command post checked. In this study, we developed a wireless communication system for respirators that provides user information and conducted an experiment to measure response time by distance according to spatial characteristics. As a result of the experiment, the response was approximately 5.09 s on average in open space, approximately 5.19 s in the location blocked by one sandwich panel, and approximately 5.79 s in the location blocked by two sandwich panels. Therefore, it was determined that the response speed was affected when the sandwich panel was 100 mm or more.

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by homozygous or compound heterozygous gain-of-function mutations in MEFV, which encodes pyrin, an inflammasome protein. Heterozygous carrier frequencies for multiple MEFV mutations are high in several Mediterranean populations, suggesting that they confer selective advantage. Among 2,313 Turkish people, we found extended haplotype homozygosity flanking FMF-associated mutations, indicating evolutionarily recent positive selection of FMF-associated mutations. Two pathogenic pyrin variants independently arose >1,800 years ago. Mutant pyrin interacts less avidly with Yersinia pestis virulence factor YopM than with wild-type human pyrin, thereby attenuating YopM-induced interleukin (IL)-1β suppression. Relative to healthy controls, leukocytes from patients with FMF harboring homozygous or compound heterozygous mutations and from asymptomatic heterozygous carriers released heightened IL-1β specifically in response to Y. pestis. Y. pestis-infected MefvM680I/M680I FMF knock-in mice exhibited IL-1-dependent increased survival relative to wild-type knock-in mice. Thus, FMF mutations that were positively selected in Mediterranean populations confer heightened resistance to Y. pestis. Familial Mediterranean fever is an autoinflammatory disease caused by gain-of-function mutations in the pyrin inflammasome. Kastner and colleagues show that mutant pyrin better resists suppression by the plague bacterium Yersinia pestis and may have been positively selected in human Middle Eastern populations.

An ideal cancer therapeutic strategy involves the selective killing of cancer cells without affecting the surrounding normal cells. However, researchers have failed to develop such methods for achieving selective cancer cell death because of shared features between cancerous and normal cells. In this study, we have developed a therapeutic strategy called the cancer-specific insertions-deletions (InDels) attacker (CINDELA) to selectively induce cancer cell death using the CRISPR-Cas system. CINDELA utilizes a previously unexplored idea of introducing CRISPR-mediated DNA double-strand breaks (DSBs) in a cancer-specific fashion to facilitate specific cell death. In particular, CINDELA targets multiple InDels with CRISPR-Cas9 to produce many DNA DSBs that result in cancer-specific cell death. As a proof of concept, we demonstrate here that CINDELA selectively kills human cancer cell lines, xenograft human tumors in mice, patient-derived glioblastoma, and lung patient-driven xenograft tumors without affecting healthy human cells or altering mouse growth.

ImportanceAlthough P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable.ObjectiveTo identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI.Design, Setting, and ParticipantsThe Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020.InterventionsPatients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer.Main Outcomes and MeasuresThe primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5).ResultsIn total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.Conclusions and RelevanceAmong patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size.Trial RegistrationClinicalTrials.gov Identifier: NCT02079194

Compared with Caucasian patients, East Asian patients have the unique risk–benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age Registration URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.

Haematopoietic stem and progenitor cells (HSPCs) have been the focus of developmental and regenerative studies, yet our understanding of the signalling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the Facilitates chromatin transcription (FACT) complex, is required for HSPC formation. Zebrafish supt16h mutants express reduced levels of Notch-signalling components, genes essential for HSPC development, due to abrogated transcription. Whereas global chromatin accessibility in supt16h mutants is not substantially altered, we observe a specific increase in p53 accessibility, causing an accumulation of p53. We further demonstrate that p53 influences expression of the Polycomb-group protein PHC1, which functions as a transcriptional repressor of Notch genes. Suppression of phc1 or its upstream regulator, p53, rescues the loss of both Notch and HSPC phenotypes in supt16h mutants. Our results highlight a relationship between supt16h, p53 and phc1 to specify HSPCs via modulation of Notch signalling.

Limited data are available on the association between low-flow time and survival in patients with in-hospital cardiac arrest (IHCA) who undergo extracorporeal cardiopulmonary resuscitation (ECPR). We evaluated data from 183 IHCA patients who underwent ECPR as a rescue procedure. Patients were divided into two groups: patients undergoing extracorporeal membrane oxygenation as an adjunct to standard cardiopulmonary resuscitation for less than 38 min (n = 110) or for longer than 38 min (n = 73). The ECPR ≤ 38 min group had a significantly greater incidence of survival to discharge compared to the ECPR &gt, 38 min group (40.0% versus 24.7%, p = 0.032). The incidence of good neurologic outcomes at discharge tended to be greater in the ECPR ≤ 38 min group than in the ECPR &gt, 38 min group (35.5% versus 24.7%, p = 0.102). The incidences of limb ischemia (p = 0.354) and stroke (p = 0.805) were similar between the two groups, but major bleeding occurred less frequently in the ECPR ≤ 38 min group compared to the ECPR &gt, 38 min group (p = 0.002). Low-flow time ≤ 38 min may reduce the risk of mortality and fatal neurologic damage and could be a measure of optimal management in patients with IHCA.

BACKGROUND Little is known about the causality and pathological mechanism underlying the association between old age and myocardial injury in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated the association between old age and myocardial injury in STEMI patients undergoing primary percutaneous coronary intervention (PCI) using cardiovascular magnetic resonance imaging (CMR). METHODS A total of 279 patients with STEMI who underwent primary PCI and CMR were enrolled. Of these, 52 patients were over the age of 70 years (18.6%, Age ≥70 group) and 227 patients were under the age of 70 years (81.4%, Age

Objectives The aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans. Background Animal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction. Methods In this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro–B-type natriuretic peptide level at 6 months. Results Among initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro–B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m2; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m2; p = 0.056) (difference −2.3 ml/m2; 95% confidence interval: −4.8 to 0.2 ml/m2; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m2; p Conclusions Ticagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534 )

Objective: To identify a genetic cause of early-onset systemic lupus erythematosus (SLE) in a large consanguineous family from Turkey and to study the mechanisms of disease. Methods: We performed whole exome sequencing (WES) and SNP array genotyping in affected and unaffected family members. Protein studies, gene expression, cytokine profiling, neutrophil extracellular trap formation, and presence of low-density granulocytes were evaluated in patient primary cells and serum samples. Results: We identified a novel homozygous loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. Sanger sequencing of 14 family members confirmed the homozygous mutation in four affected patients, and in an asymptomatic 9-year old female. Sera from patients with truncated C1r protein had low complement levels. Two affected siblings available for detailed evaluation exibited strong type I interferon inflammatory signatures despite being clinically inactive at the time of sampling. The type-I IFN transcriptional signature in patients' blood correlated with disease expressivity, whereas the neutrophil signature in patients' PBMCs was likely associated with disease severity. The affected female with the most severe phenotype, showed a stronger neutrophil signature, defined by enhanced neutrophil extracellular trap formation and the presence of low-density granulocytes. Analysis of exome data for modifying alleles suggested enrichment of common SLE-associated variants in the more severely affected patients. Lupus-associated HLA alleles or HLA haplotypes were not shared among the 4 affected subjects. Conclusion: We report a novel high-penetrance mutation in C1R as the cause of monogenic SLE. Disease expressivity in this family appears to be influenced by additional common and rare genetic variants. This article is protected by copyright. All rights reserved.

Background Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure–lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension. Methods This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome. Discussion Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients. Trial registration ClinicalTrials.gov Identifier: NCT03246555, registered on July 25, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3466-5) contains supplementary material, which is available to authorized users.

Indication of side branch (SB) intervention after main vessel (MV) stenting is not established for coronary bifurcation lesions.We evaluated 2017 patients who were treated with 1-stent technique or MV stenting as a first strategy. Patients undergoing SB intervention after MV stenting (SB intervention group, n=929) were compared to those treated with MV stenting only (no-SB intervention group, n=1088).During a median follow-up of 37months, cardiac death or myocardial infarction (MI) tended to occur less frequently in the SB intervention group than in the no-SB intervention group (1.8% versus 2.9%; adjusted hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.25-1.11; P=0.09). There was a significant interaction between SB intervention and SB stenosis after MV stenting (P for interaction0.01). Among 1077 patients with diameter stenosis of SB ≥50% after MV stenting, SB intervention was associated with a lower risk of cardiac death or MI (1.2% versus 4.2%; adjusted HR 0.22; 95% CI 0.09-0.52; P0.01). However, among 940 patients with diameter stenosis of SB50%, there was no significant difference in cardiac death or MI between the SB intervention group and the no-SB intervention group (3.5% versus 2.2%; adjusted HR 1.36; 95% CI 0.58-3.20; P=0.48).The effect of SB intervention differed according to SB stenosis after MV stenting. SB intervention may reduce cardiac death or MI in bifurcation lesions with diameter stenosis of SB ≥50% after MV stenting.

Pathogenic Yersinia, including Y. pestis, the agent of plague in humans, and Y. pseudotuberculosis, the related enteric pathogen, deliver virulence effectors into host cells via a prototypical type III secretion system to promote pathogenesis. These effectors, termed Yersinia outer proteins (Yops), modulate multiple host signaling responses. Studies in Y. pestis and Y. pseudotuberculosis have shown that YopM suppresses infection-induced inflammasome activation, however the underlying molecular mechanism is largely unknown. Here we show that YopM specifically restricts the pyrin inflammasome, which is triggered by the RhoA-inactivating enzymatic activities of YopE and YopT, in Y. pseudotuberculosis-infected macrophages. The attenuation of a yopM mutant is fully reversed in pyrin knock-out mice, demonstrating that YopM inhibits pyrin to promote virulence. Mechanistically, YopM recruits and activates the host kinases PRK1 and PRK2 to negatively regulate pyrin by phosphorylation. These results show how a virulence factor can hijack host kinases to inhibit effector-triggered pyrin inflammasome activation.

Mutations in the genes encoding pyrin and mevalonate kinase (MVK) cause distinct interleukin-1β (IL-1β)-mediated autoinflammatory diseases: familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS). Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome. The binding of 14-3-3 and PKN proteins to FMF-associated mutant pyrin was substantially decreased, and the constitutive IL-1β release from peripheral blood mononuclear cells of patients with FMF or HIDS was attenuated by activation of PKN1 and PKN2. Defects in prenylation, seen in HIDS, led to RhoA inactivation and consequent pyrin inflammasome activation. These data suggest a previously unsuspected fundamental molecular connection between two seemingly distinct autoinflammatory disorders.

최근 우리나라의 인구구조가 표주박형태의 고령화 사회로 변화함에 따라 급사의 원인이 되는 심장질환의 발생이 고령이 될수록 증가하고 있다. 심정지나 호흡이 정지된 환자에게 사용되는 인공호흡기중 전 세계적으로 보급되고 있는 공급되는 산소의 압력만으로 자동으로 작동되는 휴대용 인공호흡기의 필요성이 증가하고 있다. 이러한 휴대용 인공호흡기의구성품 및 인공호흡기에 중요시되는 성능요구사항에 따른 시험방법을 제시하고 그에 따른 인공호흡기 내부감압셋팅 변화조건에 따른 최적 성능요구조건에 적합한 내부 감압조건을 찾고자 한다.ABSTRACTRecently, it has been increasing an incidence of heart diseases which is a causative factor in sudden death as Korean pop-ulation structure has been changing to an aging society. There is growing needs for A portable ventilator which automati-cally be operated by the pressure of the supplied oxygen and has been spread worldwide. So, we would like to present testmethods in accordance with the performance requirements which are important for components of a respirator and a porta-ble ventilator itself. And also would like to find the most suitable condition of internal pressure reduction for the perfor-mance requirements according to the changing conditions of internal pressure reduction setting of a portable ventilator.Keywords : Portable resuscitator, Testing technique, Components, Automatically, Oxygen

This study examined the effects of the wind conditions, such as wind velocity and wind directions, on the performance of the mechanical smoke exhaust systems for high-rise building fires. A scaled model design and CFD simulations were used to verify the effects both quantitatively and qualitatively. The results showed that the smoke exhaust velocity of the mechanical exhaust system can be reduced by up to 17% at a wind velocity of 5 m/s (equivalent to an outdoor wind speed of 16 m/s) and a wind direction of ${\theta}

Cases of cardiac arrests due to cardiovascular ailments have increased recently., portable Current portable resuscitators which can be automatically supply oxygen operated by the pressure of supplied oxygen without manual or electronic actuators are now widely used in emergency worldwide. However, reductions in Pressure drop characteristics through the extended use of this type of resuscitator, however, is are not well-known described. This paper describes the reduction in pressure loss drop performance of the various holes in within the flow control disc of with various hole size of the portable resuscitators using on breathing resistance through the CFD simulation, and suggests the an optimum optimal design of the hole shapes for the minimization of alteration in order to minimize this pressure drops.

Ecological character displacement predicts that interspecific resource competition results in greater trait divergence between species in sympatry than in allopatry. However, other processes, such as ecological sorting, result in the same pattern of trait variation. In this study, we characterize character displacement in eight species of snail-feeding Acoptolabrus ground beetles in the Far East. Acoptolabrus exhibit divergent feeding phenotypes, including species with a slender forebody that is able to intrude into large shells and species with stout heads and mandibles for crushing small shells. The pattern of character displacement in feeding phenotypes was confirmed by multivariate analysis of body dimensions. Molecular phylogenetic analysis, divergence time estimation and biogeographical analysis revealed that sympatry and phenotypic divergence occurred repeatedly during the Pleistocene and almost simultaneously within each geographical area. Comparative analysis revealed that the evolution of feeding phenotypes best fitted a selective model with three adaptive optima, corresponding to the three cases of sympatry with a congener. Repeated coincidences of sympatry and adaptive differentiation in feeding phenotypes suggested causal relationships, although the precise order of events was difficult to discriminate. This study provides insight into the spatiotemporal dynamics of interspecific interactions and adaptive phenotypic diversification.

Purpose: Non-adherence to medications can be classified as unintentional and intentional. The aim of this study was to establish the major determinants of each non-adherence in myocardial infarction (MI). We also evaluated the effects of non-adherences on healthy behaviors. Materials and Methods: We enrolled 510 patients &gt, 1 year after MI. Nonadherences classified as unintentional or intentional were measured by a self-reported questionnaire. Polynomial and multiple regression analysis were performed to evaluate the determinant of each type of nonadherences. Results: Among patients with nonadherence, 263 (70.7%) patients were unintentionally non-adherent while 109 (29.3%) patients were intentionally non-adherent. Psychological belief and attitude were important in unintentional non-adherence (Exp(&beta, ) = 0.917, p = 0.050 for anxiety, Exp(&beta, ) = 1.191, p = 0.001 for concerns). Beliefs about medications were the strongest determinant of intentional non-adherence (Exp(&beta, ) = 0.812, p &lt, 0.001 for necessity, ) = 1.421, p &lt, 0.001 for concerns). Anxiety was important determinant of intentional non-adherence (Exp(&beta, ) = 0.889, p = 0.015). Conclusion: Psychological factors and beliefs about medication were important determinants of both types of non-adherence. Combined approaches targeting the beliefs about medications and psychological distress are needed to improve drug adherence in patients with MI.

Kim et al. identify an autoinflammatory disease in mice that is driven by IL-18, resulting from an inactivating mutation in the actin-depolymerizing cofactor Wdr1. This alteration in actin dynamics is recognized by the pyrin inflammasome and results in exaggerated monocyte IL-18 production, whereas inflammasome activation in mature macrophages is unaltered., Gain-of-function mutations that activate the innate immune system can cause systemic autoinflammatory diseases associated with increased IL-1β production. This cytokine is activated identically to IL-18 by an intracellular protein complex known as the inflammasome; however, IL-18 has not yet been specifically implicated in the pathogenesis of hereditary autoinflammatory disorders. We have now identified an autoinflammatory disease in mice driven by IL-18, but not IL-1β, resulting from an inactivating mutation of the actin-depolymerizing cofactor Wdr1. This perturbation of actin polymerization leads to systemic autoinflammation that is reduced when IL-18 is deleted but not when IL-1 signaling is removed. Remarkably, inflammasome activation in mature macrophages is unaltered, but IL-18 production from monocytes is greatly exaggerated, and depletion of monocytes in vivo prevents the disease. Small-molecule inhibition of actin polymerization can remove potential danger signals from the system and prevents monocyte IL-18 production. Finally, we show that the inflammasome sensor of actin dynamics in this system requires caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, and the innate immune receptor pyrin. Previously, perturbation of actin polymerization by pathogens was shown to activate the pyrin inflammasome, so our data now extend this guard hypothesis to host-regulated actin-dependent processes and autoinflammatory disease.

Globally, c. 0.8–1.2 million species of insects exist, with Coleoptera making up about 40% of this total. Pitfall traps for collecting ground beetles were installed at 11 study plots in Baekdudaegan mountain of Gangwon-do. Individual trapped species were counted and analyzed at each study area. This study has been carried out to provide basic data for analyzing forest health and investigating the competitive distribution among biological species in the forest environment through a field investigation on the species composition, diversity, and dominance rate of Coleoptera. Carabidae were collected using pitfall traps at the study area in Backdudaegan Mountain of Gangwon-do, and the individual number of collected species was counted. Collected ground beetles in the study area comprised 837 individuals, 14 genus, and 32 species. In this study, 217, 303, 144, and 209 individuals were found in Jinburyung, Mt. Odaesan, Mt. Taebaeksan, and Mt. Dutasan area, respectively. The abundance of ground beetles was relat...