Relationship between time of emergency department admission and adherence to the Surviving Sepsis Campaign bundle in patients with septic shock.

BACKGROUND: Nighttime hospital admission is often associated with increased mortality risk in various diseases. This study investigated compliance rates with the Surviving Sepsis Campaign (SSC) 3-h bundle for daytime and nighttime emergency department (ED) admissions and the clinical impact of compliance on mortality in patients with septic shock. METHODS: We conducted an observational study using data from a prospective, multicenter registry for septic shock provided by the Korean Shock Society from 11 institutions from November 2015 to December 2017. The outcome was the compliance rate with the SSC 3-h bundle according to the time of arrival in the ED. RESULTS: A total of 2049 patients were enrolled. Compared with daytime admission, nighttime admission was associated with higher compliance with the administration of antibiotics within 3 h (adjusted odds ratio (adjOR), 1.326; 95% confidence interval (95% CI), 1.088-1.617, p = 0.005) and with the complete SSC bundle (adjOR, 1.368; 95% CI, 1.115-1.678; p = 0.003), likely to result from the increased volume of all patients and sepsis patients admitted during daytime hours. The hazard ratios of the completion of SSC bundle for 28-day mortality and in-hospital mortality were 0.750 (95% CI 0.590-0.952, p = 0.018) and 0.714 (95% CI 0.564-0.904, p = 0.005), respectively. CONCLUSION: Septic shock patients admitted to the ED during the daytime exhibited lower sepsis bundle compliance than those admitted at night. Both the higher number of admitted patients and the higher patients to medical staff ratio during daytime may be factors that are responsible for lowering the compliance.

Pex7 selectively imports PTS2 target proteins to peroxisomes and is required for anthracnose disease development in Colletotrichum scovillei.

Pex7 is a shuttling receptor that imports matrix proteins with a type 2 peroxisomal targeting signal (PTS2) to peroxisomes. The Pex7-mediated PTS2 protein import contributes to crucial metabolic processes such as the fatty acid ß-oxidation and glucose metabolism in a number of fungi, but cellular roles of Pex7 between the import of PTS2 target proteins and metabolic processes have not been fully understood. In this study, we investigated the functional roles of CsPex7, a homolog of the yeast Pex7, by targeted gene deletion in the pepper anthracnose fungus Colletotrichum scovillei. CsPex7 was required for carbon source utilization, scavenging of reactive oxygen species, conidial production, and disease development in C. scovillei. The expression of fluorescently tagged PTS2 signal of hexokinases and 3-ketoacyl-CoA thiolases showed that peroxisomal localization of the hexokinase CsGlk1 PTS2 is dependent on CsPex7, but those of the 3-ketoacyl-CoA thiolases are independent on CsPex7. In addition, GFP-tagged CsPex7 proteins were intensely localized to the peroxisomes on glucose-containing media, indicating a role of CsPex7 in glucose utilization. Collectively, these findings indicate that CsPex7 selectively recognizes specific PTS2 signal for import of PTS2-containing proteins to peroxisomes, thereby mediating peroxisomal targeting efficiency of PTS2-containing proteins in C. scovillei. On pepper fruits, the ΔCspex7 mutant exhibited significantly reduced virulence, in which excessive accumulation of hydrogen peroxide was observed in the pepper cells. We think the reduced virulence results from the abnormality in hydrogen peroxide metabolism of the ΔCspex7 mutant. Our findings provide insight into the cellular roles of CsPex7 in PTS2 protein import system.

Classification of Mucin-Type O-Glycopeptides Using Higher-Energy Collisional Dissociation in Mass Spectrometry.

Changes in mucin-type O-glycosylation of human proteins affect protein function, immune response, and cancer progression. Since O-glycoproteins are characterized by the microheterogeneity of diverse O-glycans with no conserved sequence and the macroheterogeneity of multiple glycosylation sites on serine and/or threonine in human proteins, the assessment of different mucin types, such as Tn-antigen, core 1, and core 2, and their extended core types in O-glycopeptides, is extremely challenging. Here, we present an O-GlycoProteome Analyzer (O-GPA) that automatically classifies mucin-type O-glycosylation using higher-energy collisional dissociation (HCD) in mass spectrometry. First, we estimated the number of GlcNAc residues using the intensity ratio of GlcNAc-specific fragment ions (HexNAc-CH6O3 and HexNAc-2H2O) over GalNAc-specific fragment ions (HexNAc-C2H6O3 and HexNAc-C2H4O2) in the HCD spectrum. Furthermore, we classified the different mucin types of O-glycopeptides from characteristic B2 (HexNAc2) or Y2α (PEP + HexNAc2), and Y2ß (PEP + HexNAcHex) fragment ions, along with the number of GlcNAc. Furthermore, O-GPA automatically determined single or multiple O-glycosylation, regardless of the mucin types. The mucin type of O-glycopeptides from human urine and plasma was confirmed with an overall accuracy of 96%. We found 97 core 1, 56 core 2, 13 extended core 1, and 12 extended core 2 glycopeptides from urine; and 22 core 1, 13 core 2, 7 extended core 1, 1 extended core 2, and 1 Tn-antigen from plasma. Our strategy can be used to successfully characterize specific mucin types of O-glycoproteins in human biological samples.

Selective Identification of α-Galactosyl Epitopes in N-Glycoproteins Using Characteristic Fragment Ions from Higher-Energy Collisional Dissociation.

The α-galactosyl epitope is a terminal N-glycan moiety of glycoproteins found in mammals except in humans, and thus, it is recognized as an antigen that provokes an immunogenic response in humans. Accordingly, it is necessary to analyze the α-galactosyl structure in biopharmaceuticals or organ transplants. Due to an identical glycan composition and molecular mass between α-galactosyl N-glycans and hybrid/high-mannose-type N-glycans, it is challenging to characterize α-galactosyl epitopes in N-glycoproteins using mass spectrometry. Here, we describe a method to identify α-galactosyl N-glycopeptides in mice glycoproteins using liquid chromatography with tandem mass spectrometry with higher-energy collisional dissociation (HCD). The first measure was an absence of [YHM] ion peaks in the HCD spectra, which was exclusively observed in hybrid and/or high-mannose-type N-glycopeptides. The second complementary criterion was the ratio of an m/z 528.19 (Hex2HexNAc1) ion to m/z 366.14 (Hex1HexNAc1) ion (Im/z528/Im/z366). The measure of [Im/z528/Im/z366 > 0.3] enabled a clear-cut determination of α-galactosyl N-glycopeptides with high accuracy. In Ggta1 knockout mice, we could not find any α-galactosyl N-glycoproteins identified in WT mice plasma. Using this method, we could screen for α-galactosyl N-glycoproteins from mice spleen, lungs, and plasma samples in a highly sensitive and specific manner. Conclusively, we suggest that this method will provide a robust analytical tool for determination of α-galactosyl epitopes in pharmaceuticals and complex biological samples.

Postmortem proteomics to discover biomarkers for forensic PMI estimation.

The assessment of postmortem degradation of skeletal muscle proteins has emerged as a novel approach to estimate the time since death in the early to mid-postmortem phase (approximately 24 h postmortem (hpm) to 120 hpm). Current protein-based methods are limited to a small number of skeletal muscle proteins, shown to undergo proteolysis after death. In this study, we investigated the usability of a target-based and unbiased system-wide protein analysis to gain further insights into systemic postmortem protein alterations and to identify additional markers for postmortem interval (PMI) delimitation. We performed proteomic profiling to globally analyze postmortem alterations of the rat and mouse skeletal muscle proteome at defined time points (0, 24, 48, 72, and 96 hpm), harnessing a mass spectrometry-based quantitative proteomics approach. Hierarchical clustering analysis for a total of 579 (rat) and 896 (mouse) quantified proteins revealed differentially expressed proteins during the investigated postmortem period. We further focused on two selected proteins (eEF1A2 and GAPDH), which were shown to consistently degrade postmortem in both rat and mouse, suggesting conserved intra- and interspecies degradation behavior, and thus preserved association with the PMI and possible transferability to humans. In turn, we validated the usefulness of these new markers by classical Western blot experiments in a rat model and in human autopsy cases. Our results demonstrate the feasibility of mass spectrometry-based analysis to discover novel protein markers for PMI estimation and show that the proteins eEF1A2 and GAPDH appear to be valuable markers for PMI estimation in humans.

Prolonged MEK inhibition leads to acquired resistance and increased invasiveness in KRAS mutant gastric cancer.

Gastric cancer (GC) is one of the most common causes of cancer-associated death. However, traditional therapeutic strategies have failed to significantly improve the survival of patient with advanced GC. While KRAS mutations have been found in some patients with gastric cancer, an effective therapy to treat KRAS-driven gastric cancer has not been established yet. To provide a rationale for clinical application of kinase inhibitors targeting RAS pathways, we first determined the sensitivity of GC cell lines harboring KRAS mutations or amplification to RAS pathway inhibitors. We found that MAPK pathway inhibitors (MEKi and ERKi) were more effective than AKT inhibitor, suggesting that KRAS-driven gastric cancer cells are dependent on MAPK pathway for survival. Further, we established a KRAS mutant GC cell line with acquired resistance to MEK inhibitors in order to mimic clinical situation of kinase inhibitor resistance. A comprehensive analysis of tyrosine phosphorylation in receptor tyrosine kinases in combination with small molecule chemical library screening revealed upregulated c-MET phosphorylation in this resistance cell line with elevated sensitivity to c-MET TKI (crizotinib) and PI3K/mTOR dual inhibitor (BEZ235). We also showed that migration and invasion of resistant cells were promoted, and crizotinib and BEZ235 could inhibit this malignant phenotype. Overall, our results indicate that prolonged MAPK pathway inhibition could result in acquired resistance which is associated with increased malignant phenotype in KRAS mutant GC and pharmacological targeting c-MET and PI3K/mTOR could overcome this problem.

Role of the MoYAK1 protein kinase gene in Magnaporthe oryzae development and pathogenicity.

Conidiation and appressorium differentiation are key processes for polycyclic dissemination and infection in many pathogens. Our previous study using DNA microarray led to the discovery of the MoYAK1 gene in Magnaporthe oryzae that is orthologous to YAK1 in Saccharomyces cerevisiae. Although the mechanistic roles of YAK1 in S. cerevisiae have been described, roles of MoYAK1 in M. oryzae, a phytopathogenic fungus responsible for rice blast, remain uncharacterized. Targeted disruption of MoYAK1 results in pleiotropic defects in M. oryzae development and pathogenicity. The ΔMoyak1 mutant exhibits a severe reduction in aerial hyphal formation and conidiation. Conidia in the ΔMoyak1 are delayed in germination and demonstrate decreased glycogen content in a conidial age-dependent manner. The expression of hydrophobin-coding genes is dramatically changed in the ΔMoyak1 mutant, leading to a loss of surface hydrophobicity. Unlike the complete inability of the ΔMoyak1 mutant to develop appressoria on an inductive surface, the mutant forms appressoria of abnormal morphology in response to exogenous cyclic adenosine-5'-monophosphate and host-driven signals, which are all defective in penetrating host tissues due to abnormalities in glycogen and lipid metabolism, turgor generation and cell wall integrity. These data indicate that MoYAK1 is a protein kinase important for the development and pathogenicity of M. oryzae.

Adverse events associated with poor neurological outcome during targeted temperature management and advanced critical care after out-of-hospital cardiac arrest.

INTRODUCTION: The aim of this study was to investigate the association of adverse events (AEs) during targeted temperature management (TTM) and other AEs and concomitant treatments during the advanced critical care period with poor neurological outcome at hospital discharge in adult out-of-hospital cardiac arrest (OHCA) patients. METHODS: This was a retrospective study using Korean Hypothermia Network registry data of adult OHCA patients treated with TTM in 24 teaching hospitals throughout South Korea from 2007 to 2012. Demographic characteristics, resuscitation and post-resuscitation variables, AEs, and concomitant treatments during TTM and the advanced critical care were collected. The primary outcome was poor neurological outcome, defined as a cerebral performance category (CPC) score of 3-5 at hospital discharge. The AEs and concomitant treatments were individually entered into the best multivariable predictive model of poor neurological outcome to evaluate the associations between each variable and outcome. RESULTS: A total of 930 patients, including 704 for whom a complete dataset of AEs and covariates was available for multivariable modeling, were included in the analysis; 476 of these patients exhibited poor neurological outcome [CPC 3 = 50 (7.1%), CPC 4 = 214 (30.4%), and CPC 5 = 212 (30.1%)]. Common AEs included hyperglycemia (45.6%), hypokalemia (31.3%), arrhythmia (21.3%) and hypotension (29%) during cooling, and hypotension (21.6%) during rewarming. Bleeding (5%) during TTM was a rare AE. Common AEs during the advanced critical care included pneumonia (39.6%), myoclonus (21.9%), seizures (21.7%) and hypoglycemia within 72 hours (23%). After adjusting for independent predictors of outcome, cooling- and rewarming-related AEs were not significantly associated with poor neurological outcome. However, sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care were associated with poor neurological outcome [adjusted odds ratios (95% confidence intervals) of 3.12 (1.40-6.97), 3.72 (1.93-7.16), 4.02 (2.04-7.91), 2.03 (1.09-3.78), and 1.69 (1.03-2.77), respectively]. Alternatively, neuromuscular blocker use was inversely associated with poor neurological outcome (0.48 [0.28-0.84]). CONCLUSIONS: Cooling- and rewarming-related AEs were not associated with poor neurological outcome at hospital discharge. Sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care period were associated with poor neurological outcome at hospital discharge in our study.

Biological Control of Fusarium oxysporum, the Causal Agent of Fusarium Basal Rot in Onion by Bacillus spp.

Fusarium oxysporum is the main pathogen causing Fusarium basal rot in onion (Allium cepa L.), which incurs significant yield losses before and after harvest. Among management strategies, biological control is an environmentally safe and sustainable alternative to chemical control. In this study, we isolated and screened bacteria for antifungal activity against the basal rot pathogen F. oxysporum. Isolates 23-045, 23-046, 23-052, 23-055, and 23-056 significantly inhibited F. oxysporum mycelial growth and conidial germination. Isolates 23-045, 23-046, 23-052, and 23-056 suppressed the development of Fusarium basal rot in both onion seedlings and bulbs in pot and spray inoculation assays. Isolate 23-055 was effective in onion seedlings but exhibited weak inhibitory effect on onion bulbs. Based on analyses of the 16S rRNA and rpoB gene sequences together with morphological analysis, isolates 23-045, 23-046, 23-052, and 23-055 were identified as Bacillus thuringiensis, and isolate 23-056 as Bacillus toyonensis. All five bacterial isolates exhibited cellulolytic, proteolytic, and phosphate-solubilizing activity, which may contribute to their antagonistic activity against onion basal rot disease. Taken together B. thuringiensis 23-045, 23-046, 23-052, and 23-055 and B. toyonensis 23-056 have potential for the biological control of Fusarium basal rot in onion.

Factors Affecting the Length of Stay in the Emergency Department in Psychiatric Emergency Patients in the COVID-19 Pandemic Context.

To reduce overcrowding in emergency departments (ED), which is a serious international problem, it is important to reduce the length of ED stay (ED LOS) of emergency patients. In particular, due to the COVID 19 pandemic, psychiatric emergency patients spent much longer in ED. This study was conducted to identify the characteristics of psychiatric emergency patients who visited the ED during the COVID-19 pandemic and to identify factors affecting ED LOS. This retrospective study was conducted on adult patients aged 19 years or older who visited a psychiatric emergency center operated by an ED from 1 May 2020 to 31 April 2021 because of the COVID-19 pandemic. In this study, the average ED LOS of psychiatric emergency patients was 7.8 h. Factors affecting ED LOS for over 12 h were isolation (OR = 2.39, CI = 1.409-4.052), unaccompanied police officers (OR = 2.106, CI = 1.338-3.316), night-time visits (OR = 2.127, CI = 1.357-3.332), use of sedatives (OR = 1.671, CI = 1.030-2.713), and restraints (OR = 1.968, CI = 1.172-4.895). The ED LOS of psychiatric emergency patients is longer than that of general emergency patients, and a long ED LOS causes ED overcrowding. To reduce the ED LOS of psychiatric emergency patients, they must be accompanied by a police officer when visiting the ED, and the treatment process should be reorganized so that a psychiatrist can promptly intervene. Furthermore, it is necessary to reorganize the isolation guidelines and admission criteria for mental emergency patients.

Identification of Fusarium Basal Rot Pathogens of Onion and Evaluation of Fungicides against the Pathogens.

Onion (Allium cepa L.) is an economically important vegetable crop worldwide. However, various fungal diseases, including Fusarium basal rot (FBR), neck rot, and white rot, reduce onion production or bulb storage life. FBR caused by Fusarium species is among the most destructive onion diseases. In this study, we identified Fusarium species associated with FBR in Jeolla and Gyeongsang Provinces in South Korea and evaluated fungicides against the pathogens. Our morphological and molecular analyses showed that FBR in onions is associated with Fusarium commune, Fusarium oxysporum, and Fusarium proliferatum. We selected seven fungicides (fludioxonil, hexaconazole, mandestrobin, penthiopyrad, prochloraz-manganese, pydiflumetofen, and tebuconazole) and evaluated their inhibitory effects on mycelial growth of the pathogens at three different concentrations (0.01, 0.1, and 1 mg/mL). We found that prochloraz-manganese was highly effective, inhibiting 100% of the mycelial growth of the pathogens at all concentrations, followed by tebuconazole. Fludioxonil showed < 50% inhibition at 1 mg/mL for the tested isolates.

Quantitative proteomic analysis of human serum using tandem mass tags to predict cardiovascular risks in patients with psoriasis.

Although biomarker candidates associated with psoriasis have been suggested, those for predicting the risk of cardiovascular disease (CVD) early in patients with psoriasis are lacking. We aimed to identify candidate biomarkers that can predict the occurrence of CVD in psoriasis patients. We pursued quantitative proteomic analysis of serum samples composed of three groups: psoriasis patients with and those without CVD risk factors, and healthy controls. Age/Sex-matched serum samples were selected and labeled with 16-plex tandem mass tag (TMT) and analyzed using liquid chromatography-mass spectrometry and subsequent verification with ELISA. Of the 184 proteins that showed statistical significance (P-value < 0.05) among the three groups according to TMT-based quantitative analysis, 98 proteins showed significant differences (> 2.0-fold) between the psoriasis groups with and without CVD risk factors. Verification by ELISA revealed that caldesmon (CALD1), myeloid cell nuclear differentiation antigen (MNDA), and zyxin (ZYX) levels were significantly increased in the psoriasis group with CVD risk factors. Further network analysis identified pathways including integrin signaling, which could be related to platelet aggregation, and actin cytoskeleton signaling. Three novel candidates (MNDA, ZYX, and CALD1) could be potential biomarkers for predicting CVD risks in psoriasis patients. We expect these biomarker candidates can be used to predict CVD risk in psoriasis patients in clinical settings although further studies including large validation are needed.

The CsSTE50 Adaptor Protein in Mitogen-Activated Protein Kinase Cascades Is Essential for Pepper Anthracnose Disease of Colletotrichum scovillei.

Anthracnose, caused by the ascomycete fungus Colletotrichum scovillei, is a destructive disease in pepper. The fungus germinates and develops an infection structure called an appressorium on the plant surface. Several signaling cascades, including cAMP-mediated signaling and mitogen-activated protein kinase (MAPK) cascades, are involved in fungal development and pathogenicity in plant pathogenic fungi, but this has not been well studied in the fruit-infecting fungus C. scovillei. Ste50 is an adaptor protein interacting with multiple upstream components to activate the MAPK cascades. Here, we characterized the CsSTE50 gene of C. scovillei, a homolog of Magnaporthe oryzae MST50 that functions in MAPK cascades, by gene knockout. The knockout mutant ΔCsste50 had pleiotropic phenotypes in development and pathogenicity. Compared with the wild-type, the mutants grew faster and produced more conidia on regular agar but were more sensitive to osmotic stress. On artificial and plant surfaces, the conidia of the mutant showed significantly reduced germination and failed to form appressoria. The mutant was completely non-pathogenic on pepper fruits with or without wounds, indicating that pre-penetration and invasive growth were both defective in the mutant. Our results show that the adaptor protein CsSTE50 plays a role in vegetative growth, conidiation, germination, appressorium formation, and pathogenicity in C. scovillei.

NADPH Oxidases Are Required for Appressorium-Mediated Penetration in Colletotrichum scovillei-Pepper Fruit Pathosystem.

NADPH oxidase (Nox) complexes are known to play essential roles in differentiation and proliferation of many filamentous fungi. However, the functions of Noxs have not been elucidated in Colletotrichum species. Therefore, we set out to characterize the roles of Nox enzymes and their regulators in Colletotrichum scovillei, which causes serious anthracnose disease on pepper fruits in temperate and subtropical and temperate region. In this study, we generated targeted deletion mutants for CsNox1, CsNox2, CsNoxR, and CsNoxD via homologous recombination. All deletion mutants were normal in mycelial growth, conidiation, conidial germination, and appressorium formation, suggesting that CsNox1, CsNox2, CsNoxR, and CsNoxD are not involved in those developmental processes. Notably, conidia of ΔCsnox2 and ΔCsnoxr, other than ΔCsnox1 and ΔCsnoxd, failed to cause anthracnose on intact pepper fruits. However, they still caused normal disease on wounded pepper fruits, suggesting that Csnox2 and CsnoxR are essential for penetration-related morphogenesis in C. scovillei. Further observation proved that ΔCsnox2 and ΔCsnoxr were unable to form penetration peg, while they fully developed appressoria, revealing that defect of anthracnose development by ΔCsnox2 and ΔCsnoxr resulted from failure in penetration peg formation. Our results suggest that CsNox2 and CsNoxR are critical for appressorium- mediated penetration in C. scovillei-pepper fruit pathosystem, which provides insight into understanding roles of Nox genes in anthracnose disease development.

CsPOM1, a DYRK Family Kinase, Plays Diverse Roles in Fungal Development, Virulence, and Stress Tolerance in the Anthracnose Pathogen Colletotrichum scovillei.

Colletotrichum scovillei is the major anthracnose fungus of sweet pepper and chili pepper (Capsicum annuum L.), causing significant losses in the yield and quality of the pepper fruits. Molecular mechanisms governing development and pathogenicity have been widely studied in many foliar fungal pathogens, but the information on fruit diseases is still limited. In this study, we determined the functional roles of the dual-specificity tyrosine phosphorylation-regulated kinase CsPOM1 in C. scovillei. Knockout mutant for CsPOM1 gene was obtained via homology-dependent gene replacement. The ΔCspom1 mutant exhibited a reduction in vegetative growth on osmotic stress, surface hydrophobicity, and conidiation compared with wild-type. Conidia of the ΔCspom1 mutant were already two-celled before inoculation on an induction surface, indicating that CsPOM1 negatively regulates conidial cell division. The ΔCspom1 mutant, similar to wild-type, formed appressoria on the plant surface, but was significantly reduced on hydrophobic coverslips, probably due to a defect in the recognition of surface hydrophobicity. Treatment of conidia with cutin monomers restored appressorium formation on hydrophobic coverslips in the ΔCspom1 mutant. On pepper fruits, the ΔCspom1 mutant exhibited delayed penetration and invasive growth, leading to significantly reduced virulence. Collectively, the results showed that CsPOM1 is important for stress tolerance, conidiation, surface hydrophobicity, appressorium formation, and virulence in C. scovillei.

Mitogen-Activated Protein Kinase CsPMK1 Is Essential for Pepper Fruit Anthracnose by Colletotrichum scovillei.

The phytopathogenic fungus Colletotrichum scovillei, belonging to the Colletotrichum acutatum species complex, causes severe anthracnose disease on several fruits, including chili pepper (Capsicum annuum). However, the molecular mechanisms underlying the development and pathogenicity of Colletotrichum scovillei are unclear. The conserved Fus3/Kss1-related MAPK regulates fungal development and pathogenicity. Here, the role of CsPMK1, orthologous to Fus3/Kss1, was characterized by phenotypic comparison of a target deletion mutant (ΔCspmk1). The mycelial growth and conidiation of ΔCspmk1 were normal compared to that of the wild type. ΔCspmk1 produced morphologically abnormal conidia, which were delayed in conidial germination. Germinated conidia of ΔCspmk1 failed to develop appressoria on inductive surfaces of hydrophobic coverslips and host plants. ΔCspmk1 was completely defective in infectious growth, which may result from failure to suppress host immunity. Furthermore, ΔCspmk1 was impaired in nuclear division and lipid mobilization during appressorium formation, in response to a hydrophobic surface. CsPMK1 was found to interact with CsHOX7, a homeobox transcription factor essential for appressorium formation, via a yeast two-hybridization analysis. Taken together, these findings suggest that CsPMK1 is required for fungal development, stress adaptation, and pathogenicity of C. scovillei.

Impact of COVID-19 Pandemic on Management and Outcomes in Patients with Septic Shock in the Emergency Department.

This study aimed to determine the impact of modifications in emergency department (ED) practices caused by the coronavirus disease 2019 (COVID-19) pandemic on the clinical outcomes and management of patients with septic shock. We performed a retrospective study. Patients with septic shock who presented to the ED between 1 January 2018 and 19 January 2020 were allocated to the pre-COVID-19 group, whereas those who presented between 20 January 2020 and 31 December 2020 were assigned to the post-COVID-19 group. We used propensity score matching to compare the sepsis-related interventions and clinical outcomes. The primary outcome measure was in-hospital mortality. Of the 3697 patients included, 2254 were classified as pre-COVID-19 and 1143 as post-COVID-19. A total of 1140 propensity score-matched pairings were created. Overall, the in-hospital mortality rate was 25.5%, with no statistical difference between the pre- and post-COVID-19 groups (p = 0.92). In a matched cohort, the post-COVID-19 group had delayed lactate measurement, blood culture test, and infection source control (all p < 0.05). There was no significant difference in time to antibiotics (p = 0.19) or vasopressor administration (p = 0.09) between the groups. Although sepsis-related interventions were delayed during the COVID-19 pandemic, there was no significant difference in the in-hospital mortality between the pre- and post-COVID-19 groups.

Hormonal responses upon return of spontaneous circulation after cardiac arrest: a retrospective cohort study.

INTRODUCTION: Cardiac arrest is often fatal and can be extremely stressful to patients, even if spontaneous rhythm is returned. The purpose of this study was to analyze the hormonal response after return of spontaneous circulation (ROSC). METHODS: This is a retrospective review of the chart and laboratory findings in a single medical facility. The patients admitted to the intensive care unit after successful resuscitation after out-of-hospital cardiac arrest were retrospectively identified and evaluated. Patients with hormonal diseases, patients who received cortisol treatment, those experiencing trauma, and pregnant women were excluded. Serum cortisol, adrenocorticotropic hormone (ACTH), and anti-diuretic hormone (ADH (vasopressin)) were analyzed and a corticotropin-stimulation test was performed. Mortality at one week and one month after admission, and neurologic outcome (cerebral performance category (CPC)) one month after admission were evaluated. RESULTS: A total of 117 patients, including 84 males (71.8%), were evaluated in this study. One week and one month after admission, 87 (74.4%) and 65 patients (55.6%) survived, respectively. Relative adrenal insufficiency, and higher plasma ACTH and ADH levels were associated with shock-related mortality (P = 0.046, 0.005, and 0.037, respectively), and ACTH and ADH levels were also associated with late mortality (P = 0.002 and 0.004, respectively). Patients with relative adrenal insufficiency, ACTH ≧5 pg/mL, and ADH ≧30 pg/mL, had a two-fold increased risk of a poor outcome (shock-related mortality): (odds ratio (OR), 2.601 and 95% confidence interval (CI), 1.015 to 6.664; OR, 2.759 and 95% CI, 1.060 to 7.185; OR, 2.576 and 95% CI, 1.051 to 6.313, respectively). Thirty-five patients (29.9%) had a good CPC (1 to 2), and 82 patients (70.1%) had a bad CPC (3 to 5). Age ≧50 years and an ADH ≧30 pg/mL were associated with a bad CPC (OR, 4.564 and 95% CI, 1.794 to 11.612; OR, 6.568 and 95% CI, 1.918 to 22.483, respectively). CONCLUSIONS: The patients with relative adrenal insufficiency and higher blood levels of ACTH and ADH upon ROSC after cardiac arrest had a poor outcome. The effectiveness of administration of cortisol and ADH to patients upon ROSC after cardiac arrest is uncertain and additional studies are needed.

Effectiveness of each target body temperature during therapeutic hypothermia after cardiac arrest.

PURPOSE: According to the 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation, unconscious adult patients with a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest should be cooled to 32°C to 34°C for 12 to 24 hours. However, it is unclear which target temperature is more adequate. In this study, we prospectively evaluated the outcome and adverse effects following 3 target temperatures (32°C, 33°C, and 34°C) during therapeutic hypothermia with ROSC after out-of-hospital cardiac arrest. METHODS: This is a prospective study of patients with ROSC (>24 hours) after out-of-hospital cardiac arrest who were admitted to the intensive care unit in a tertiary hospital and underwent therapeutic hypothermia during a 22-month period between March 2007 and December 2008. RESULTS: Sixty-two patients were included. The number of male patients was 44. The mean (SD) ages of the patients was 54.61 (2.002) years. There were 13, 22, and 28 patients who were enrolled in the target temperatures (32°C, 33°C, and 34°C, respectively). There were no significant differences after each target temperature with respect to mortality and neurologic outcomes. Regarding adverse effects, hypotension during the maintenance of therapeutic hypothermia significantly increased when the target temperature was 32°C (P = .023). Based on multivariate analysis, hypotension during the maintenance of therapeutic hypothermia was increased more than 6 times at 32°C compared with 33°C (odds ratio, 6.800; 95% confidence interval, 1.428-32.373). CONCLUSION: When performing therapeutic hypothermia in patients with ROSC after an out-of-hospital cardiac arrest, the target temperature would be set to 33°C or 34°C, rather than 32°C. Further multicenter randomized controlled studies may be needed in the future.

Antagonistic and Plant Growth-Promoting Effects of Bacillus velezensis BS1 Isolated from Rhizosphere Soil in a Pepper Field.

Pepper (Capsicum annuum L.) is an important agricultural crop worldwide. Recently, Colletotrichum scovillei, a member of the C. acutatum species complex, was reported to be the dominant pathogen causing pepper anthracnose disease in South Korea. In the present study, we isolated bacterial strains from rhizosphere soil in a pepper field in Gangwon Province, Korea, and assessed their antifungal ability against C. scovillei strain KC05. Among these strains, a strain named BS1 significantly inhibited mycelial growth, appressorium formation, and disease development of C. scovillei. By combined sequence analysis using 16S rRNA and partial gyrA sequences, strain BS1 was identified as Bacillus velezensis, a member of the B. subtilis species complex. BS1 produced hydrolytic enzymes (cellulase and protease) and iron-chelating siderophores. It also promoted chili pepper (cv. Nockwang) seedling growth compared with untreated plants. The study concluded that B. velezensis BS1 has good potential as a biocontrol agent of anthracnose disease in chili pepper caused by C. scovillei.