FTO negatively regulates the cytotoxic activity of natural killer cells.

N6 -Methyladenosine (m6 A) is the most abundant epitranscriptomic mark and plays a fundamental role in almost every aspect of mRNA metabolism. Although m6 A writers and readers have been widely studied, the roles of m6 A erasers are not well-understood. Here, we investigate the role of FTO, one of the m6 A erasers, in natural killer (NK) cell immunity. We observe that FTO-deficient NK cells are hyperactivated. Fto knockout (Fto-/- ) mouse NK cells prevent melanoma metastasis in vivo, and FTO-deficient human NK cells enhance the antitumor response against leukemia in vitro. We find that FTO negatively regulates IL-2/15-driven JAK/STAT signaling by increasing the mRNA stability of suppressor of cytokine signaling protein (SOCS) family genes. Our results suggest that FTO is an essential modulator of NK cell immunity, providing a new immunotherapeutic strategy for allogeneic NK cell therapies.

Δ133p53 coordinates ECM-driven morphogenesis and gene expression in three-dimensional mammary epithelial acini.

Growing evidence indicates that p53 (encoded by TP53) has a crucial role in normal tissue development. The role of the canonical p53 (p53α) and its 12 isoforms in development and homeostasis of healthy tissue remains poorly understood. Here, we demonstrate that the Δ133p53 isoforms, the three short isoforms of p53, respond specifically to laminin-111 and play an important regulatory role in formation of mammary organoids in concert with p53α. We demonstrate that down-modulation of Δ133p53 isoforms leads to changes in gene expression of the extracellular matrix molecules fibronectin (FN), EDA+-FN, laminin α5 and laminin α3 in human breast epithelial cells. These changes resulted in increased actin stress fibers and enhanced migratory behavior of cells in two-dimensional culture. We found that α5ß1-integrin coupled with the extracellularly deposited EDA+-FN activates the Akt signaling pathway in three-dimensional (3D) culture when Δ133p53 is dysregulated. Cells that do not express detectable Δ133p53 isoforms or express low levels of these isoforms failed to form polarized structures in 3D. These results uncover that Δ133p53 isoforms coordinate expression and deposition of organ-specific ECM molecules that are critical for maintenance of tissue architecture and function.

Mass spectrometry imaging of untreated wet cell membranes in solution using single-layer graphene.

We report a means by which atomic and molecular secondary ions, including cholesterol and fatty acids, can be sputtered through single-layer graphene to enable secondary ion mass spectrometry (SIMS) imaging of untreated wet cell membranes in solution at subcellular spatial resolution. We can observe the intrinsic molecular distribution of lipids, such as cholesterol, phosphoethanolamine and various fatty acids, in untreated wet cell membranes without any labeling. We show that graphene-covered cells prepared on a wet substrate with a cell culture medium reservoir are alive and that their cellular membranes do not disintegrate during SIMS imaging in an ultra-high-vacuum environment. Ab initio molecular dynamics calculations and ion dose-dependence studies suggest that sputtering through single-layer graphene occurs through a transient hole generated in the graphene layer. Cholesterol imaging shows that methyl-ß-cyclodextrin preferentially extracts cholesterol molecules from the cholesterol-enriched regions in cell membranes.

Scaling up polarized RPE cell supernatant production on parylene membrane.

Age-related macular degeneration (AMD), a leading cause of vision loss, primarily arises from the degeneration of retinal pigment epithelium (RPE) and photoreceptors. Current therapeutic options for dry AMD are limited. Encouragingly, cultured RPE cells on parylene-based biomimetic Bruch's membrane demonstrate characteristics akin to the native RPE layer. In this study, we cultivated human embryonic stem cell-derived polarized RPE (hESC-PRPE) cells on parylene membranes at both small- and large-scale settings, collecting conditioned supernatant, denoted as PRPE-SF. We conducted a comprehensive analysis of the morphology of the cultured hESC-RPE cells and the secreted growth factors in PRPE-SF. To evaluate the in vivo efficacy of these products, the product was administered via intravitreal injections of PRPE-SF in immunodeficient Royal College of Surgeons (iRCS) rats, a model for retinal degeneration. Our study not only demonstrated the scalability of PRPE-SF production while maintaining RPE cell phenotype but also showed consistent protein concentrations between small- and large-scale batches. We consistently identified 10 key factors in PRPE-SF, including BMP-7, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6, MANF, PEDF, PDGF-AA, TGFß1, and VEGF. Following intravitreal administration of PRPE-SF, we observed a significant increase in the thickness of the outer nuclear layer (ONL) and photoreceptor preservation in iRCS rats. Furthermore, correlation analysis revealed that IGFBP-3, IGFBP-4, MANF, PEDF, and TGFß1 displayed positive associations with in vivo bioactivity, while GDF-15 exhibited a negative correlation. Overall, this study highlights the feasibility of scaling up PRPE-SF production on parylene membranes without compromising its essential constituents. The outcomes of PRPE-SF administration in an animal model of retinal degeneration present substantial potential for photoreceptor preservation. Moreover, the identification of candidate surrogate potency markers, showing strong positive associations with in vivo bioactivity, lays a solid foundation for the development of a promising therapeutic intervention for retinal degenerative diseases.

Burden and preparedness of care partners of people living with amyotrophic lateral sclerosis at home in Korea: A care partner survey.

INTRODUCTION/AIMS: The care burden of people living with amyotrophic lateral sclerosis (pALS) increases with disease progression. This study aimed to investigate the home care status and preparedness of care partners of pALS (cALS) in Korea. METHODS: An online survey was conducted with family care partners of patients diagnosed with ALS for over 1 year in 2022. The data collected included care time, depression evaluated using the patient health questionnaire-9 (PHQ-9), preparedness for caregiving scale (PCS), and caregiver competence scale (CCS). Results were compared based on whether the pALS underwent a tracheostomy or not. RESULTS: Ninety-eight cALS of 98 pALS participated in the study, of whom 59 pALS had undergone tracheostomy. Among the cALS, 60.2% were spouses, and 34.7% were children. The cALS took care of the patients for 13 (8-20) hours/day (median, interquartile range [IQR]) on weekdays and 15 (10-24) h/day on weekends. Among the cALS, 91.8% were depressed, and 28.6% had severe depression. The median (IQR) PCS and CCS scores were low (11/32 (8-15) and 8/20 (8-11), respectively), and both were lower in those caring for patients without than with tracheostomy (p < .001 and p < .02, respectively). Most cALS (77.6%) wished to continue caring for their pALS at home. DISCUSSION: Family care partners of pALS spend more than half of each day caring for patients and are often depressed. Most cALS preferred providing care at home, but felt ill-prepared. Designing home-based medical care is necessary for pALS to thrive at home.

Comparison between the GastroPanel test and the serum pepsinogen assay interpreted with the ABC method-A prospective study.

BACKGROUND AND AIMS: This study aimed to validate Helicobacter pylori serological and pepsinogen (PG) assays for detecting infection and gastric neoplasm. METHODS: Individuals who underwent serum Chorus H. pylori and HBI PG assays were included from May to September 2023. The GastroPanel test was performed using the same blood sample. HBI assay findings were interpreted with the ABC method using the criteria of corpus atrophy (PG I ≤ 70 ng/mL & I/II ≤3) and advanced corpus atrophy (PG I ≤ 30 ng/mL & I/II ≤2). RESULTS: A total of 144 H. pylori-infected and 184 non-infected Koreans were analyzed. The Chorus test (sensitivity 97.2%, specificity 89.1%) showed higher area under the curve (0.993 vs. 0.972, p = 0.003) than the GastroPanel test (sensitivity 95.8%, specificity 86.4%). Using the GastroSoft application, the incidence of gastric neoplasms was highest in the corpus atrophy group (50%), followed by the low acid-output (25.8%), H. pylori infection (11.6%), and antral atrophy (9.1%) groups. There were no gastric neoplasms in the normal and high acid output groups. Using the ABC method, the incidence of gastric neoplasms was highest in the corpus atrophy groups (23.8% in Groups C and D), followed by Group B (12.3%) and Group A (2.4%). Corpus atrophy interpreted with the GastroSoft showed poor agreement (k = 0.225) with corpus atrophy interpreted with the ABC method, whereas it showed excellent agreement (k = 0.854) with advanced corpus atrophy. CONCLUSIONS: Although the Chorus test was more accurate than the GastroPanel test, both assays discriminated high-risk individuals by detecting atrophy or infection. There were no gastric neoplasms in the normal or high acid-output groups (GastroSoft application), and gastric neoplasm incidence was lowest in Group A (ABC method). Corpus atrophy determined by GastroSoft application is more consistent with advanced corpus atrophy determined by the ABC method than is corpus atrophy.

Current Status of Diagnosis and Treatment of Colorectal Cancer in Asian Countries: A Questionnaire Survey.

INTRODUCTION: Diagnostic and therapeutic methods for colorectal cancer (CRC) have advanced; however, they may be inaccessible worldwide, and their widespread use is challenging. This questionnaire survey investigates the current status of diagnosis and treatment of early-stage CRC in Asian countries. METHODS: Responses to the questionnaire were obtained from 213 doctors at different institutions in 8 countries and regions. The questionnaire consisted of 39 questions on the following four topics: noninvasive diagnosis other than endoscopy (6 questions), diagnosis by magnification and image-enhanced endoscopy (IEE) including artificial intelligence (AI) (10 questions), endoscopic submucosal dissection (ESD), proper use among other therapeutic methods (11 questions), and pathologic diagnosis and surveillance (12 questions). RESULTS: Although 101 of 213 respondents were affiliated with academic hospitals, there were disparities among countries and regions in the dissemination of advanced technologies, such as IEE, AI, and ESD. The NICE classification is widely used for the diagnosis of colorectal tumors using IEE, while the JNET classification with magnification was used in countries such as Japan (65/70, 92.9%) and China (16/22, 72.7%). Of the 211 respondents, 208 (98.6%) assumed that en bloc resection should be achieved for carcinomas, and 180 of 212 (84.9%) believed that ESD was the most suitable in cases with a diameter larger than 2 cm. However, colorectal ESD is not widespread in countries such as Thailand, the Philippines, and Indonesia. CONCLUSION: The promotion of advanced technologies and education should be continual to enable more people to benefit from them.

Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights.

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development.

MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid ß plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aß deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aß burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.

Epidemiology and characteristics of emergency department utilization by patients with amyotrophic lateral sclerosis in Korea from 2016 to 2020: A nationwide study.

INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) inevitably visit the emergency department (ED) due to their increased risk of respiratory failure and mobility limitations. However, nationwide data on ED visits by patients with ALS are limited. This study investigated the characteristics of patients with ALS-related ED visits. METHODS: We conducted a cross-sectional study from 2016 to 2020, utilizing a nationwide ED database. The total number of patients with ALS who visited the ED and their primary reasons for visiting/diagnoses were analyzed. RESULTS: In total, 6036 visits to the ED were made by patients with ALS. Of these, 41.8% arrived by ambulance and 27.7% spent >9 h in the ED. Following ED treatment, 57.4% were hospitalized, including 19.3% admitted to the intensive care unit (ICU) and 5.4% who died in the hospital. The primary reasons for ALS-related ED visits were dyspnea (35.2%), feeding tube problems (10.1%), fever (7.8%), and mental status changes (3.6%). The most common diagnoses were pneumonia (14.5%), respiratory failure (5.7%), dyspnea (5.5%), aspiration pneumonia (4.3%), and tracheostomy complications (3.4%). DISCUSSION: Reasons for ED visits for patients with ALS include acute respiratory distress, as well as concerns related to tube feeding and tracheostomy. To reduce the risk of patients with ALS requiring ED visits, it is essential to ensure the provision of timely respiratory support and high-quality home-based medical care teams that can support and address patients before their condition deteriorates.

Sphingomonas oryzagri sp. nov., isolated from a rice field.

A Gram-stain-negative, aerobic, short rod-shaped and motile novel bacterial strain, designated MAHUQ-71T, was isolated from the soil of a rice field. The colonies were observed to be milky yellow-coloured, smooth, spherical and 0.1-0.4 mm in diameter when grown on Reasoner's 2A agar medium for 2 days. Strain MAHUQ-71T was found to be able to grow at 15-37 °C, pH 5.0-10.0 and with 0-3.0 % NaCl (w/v). The strain was found to be positive for the catalase test, but negative for the oxidase test. The strain was positive for hydrolysis of aesculin and Tween 20. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Sphingomonas and to be closely related to Sphingomonas chungangi MAH-6T (98.5 % sequence similarity), Sphingomonas polyaromaticivorans B2-7T (98.4 %) and Sphingomonas oligoaromativorans SY-6T (96.6 %). Strain MAHUQ-71T has a draft genome size of 4 255 278 bp (10 contigs), annotated with 4098 protein-coding genes, 47 tRNA and three rRNA genes. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain MAHUQ-71T and the closest type strain S. chungangi MAH-6T were in the range of 85.6 and 30.6 %, respectively. The genomic DNA G+C content was determined to be 66.7 mol%. The predominant isoprenoid quinone was ubiquinone 10. The major fatty acids were identified as summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C16 : 0 and C14 : 0 2OH. The main polar lipids were phosphatidylcholine, phosphatidylethanolamine, diphosphatidylglycerol and sphingoglycolipid. On the basis of dDDH and ANI values, as well as the results of genotypic, chemotaxonomic and physiological analyses, strain MAHUQ-71T represents a novel species within the genus Sphingomonas, for which the name Sphingomonas oryzagri sp. nov. is proposed, with MAHUQ-71T (=KACC 22252T=CGMCC 1.19065T) as the type strain.

Solitalea agri sp. nov., a new member of the genus Solitalea isolated from rhizospheric soil of a jujube tree.

A Gram-stain negative, aerobic, rod-shaped and creamy pink-coloured bacterium, designated MAHUQ-68T, was isolated from rhizospheric soil of a jujube tree. Colonies grew at 10-40 °C (optimum, 28 °C), pH 6.0-9.0 (optimum pH, 7.0) and in the presence of 0-1.5 % NaCl (optimum 0-0.5 %). Positive for both catalase and oxidase activity. Strain MAHUQ-68T hydrolysed casein, starch, aesculin and l-tyrosine. Based on the results of phylogenetic analysis using 16S rRNA gene and genome sequences, strain MAHUQ-68T clustered together within the genus Solitalea. The closest members were Solitalea longa HR-AVT (98.8 % sequence similarity), Solitalea canadensis DSM 3403T (96.9 %) and Solitalea koreensis R2A36-4T (94.0 %). The genome of strain MAHUQ-68 T was 4 250 173 bp long with 68 scaffolds and 3 570 protein-coding genes. The genomic DNA G+C content of the type strain was 38.0 mol%. The average nucleotide identity and in silico DNA-DNA hybridization values between strain MAHUQ-68T and its closest relatives were 72.0-81.4% and 19.8-24.3 %, respectively. The major cellular fatty acids were iso-C15 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). The main respiratory quinone was menaquinone-7. The polar lipids comprised phosphatidylethanolamine, an unidentified aminolipid and four unidentified lipids. Based on these data, strain MAHUQ-68T represents a novel species in the genus Solitalea, for which the name Solitalea agri sp. nov. is proposed. The type strain is MAHUQ-68T (=KACC 22249T=CGMCC 1.19062T).

Sphingobium agri sp. nov., isolated from rhizospheric soil of eggplant.

A Gram-stain-negative, aerobic, short rod-shaped and motile bacterial strain, designated MAH-33T, was isolated from rhizospheric soil of eggplant. The colonies were observed to be yellow-coloured, smooth, spherical and 0.1-0.3 mm in diameter when grown on TSA agar medium for 2 days. Strain MAH-33T was found to be able to grow at 10-40 °C, at pH 5.0-10.0 and at 0-3.0 % NaCl (w/v). The strain was found to be positive for both oxidase and catalase tests. The strain was positive for hydrolysis of tyrosine and aesculin. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Sphingobium and to be closely related to Sphingobium quisquiliarum P25T (98.4 % similarity), Sphingobium mellinum WI4T (97.8 %), Sphingobium fuliginis TKPT (97.3 %) and Sphingobium herbicidovorans NBRC 16415T (96.9 %). The novel strain MAH-33T has a draft genome size of 3 908 768 bp (28 contigs), annotated with 3689 protein-coding genes, 45 tRNA and three rRNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strain MAH-33T and closely related type strains were in the range of 79.8-81.6 % and 23.2-24.5 %, respectively. The genomic DNA G+C content was determined to be 62.2 %. The predominant isoprenoid quinone was ubiquinone 10. The major fatty acids were identified as C16 : 0 and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipids identified in strain MAH-33T were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, sphingoglycolipid, phosphatidylcholine; one unknown phospholipid and one unknown lipid. On the basis of digital DNA-DNA hybridization, ANI value, genotypic analysis, chemotaxonomic and physiological data, strain MAH-33T represents a novel species within the genus Sphingobium, for which the name Sphingobium agri sp. nov. is proposed, with MAH-33T (=KACC 19973T = CGMCC 1.16609T) as the type strain.

Twice-daily intake of bismuth-based quadruple therapy for first-line Helicobacter pylori eradication: A retrospective study on 10-day, 14-day, and half-dose antibiotic therapy.

BACKGROUND/AIMS: In areas with >15% clarithromycin resistance, bismuth-based quadruple therapy is recommended for first-line Helicobacter pylori eradication. This study aimed to determine the efficacy of the twice-daily intake of bismuth-based quadruple therapy among 10-day, 14-day, and half-dose antibiotic regimens. METHODS: From May 2021 to March 2023, H. pylori-infected Korean adults were administered tetracycline (1 g), metronidazole (750 mg), bismuth potassium citrate (300 mg), and lansoprazole (30 mg) twice daily, after breakfast and dinner, for 10 days. The regimen was administered for 14 days if the body weight was ≥70 kg or if the patient had reinfection. Half doses of antibiotics were administered for 14 days if there was a risk of drug interactions or if the patient was aged ≥75 years. The 13 C-urea breath test was performed after 6 weeks. RESULTS: Among the 1258 infected Koreans, 85.1% (412/484) in the 10-day, 84.3% (498/591) in the 14-day, and 86.3% (158/183) in the half-dose antibiotic groups followed the instructions. In the per-protocol (PP) analysis, eradication rates were higher in the 10-day (90.5%, p = 0.019) and 14-day (90.2%, p = 0.023) groups than in the half-dose group (83.5%). In the intention-to-treat (ITT) analysis, eradication rates were higher in the 10-day group (80.6%) than in the half-dose group (73.2%, p = 0.039). In the half-dose group, the eradication rate was lower in patients aged ≥75 years (PP: 74.6%, ITT: 66.2%) than in those with a risk of drug interactions (PP: 89.7% [p = 0.017], ITT: 82.4% [p = 0.019]). CONCLUSIONS: Twice-daily intake of bismuth-based quadruple therapy for 10-14 days showed an eradication rate of >90% in the PP analysis. A 10-day regimen could be administered to eradication-naive patients with a body weight below 70 kg. A half-dose antibiotic regimen might be recommended to patients with a risk of drug interactions but not to those aged ≥75 years simply due to old age.

Effects of a Designated Ambulance Team Response on Prehospital Return of Spontaneous Circulation and Advanced Cardiac Life Support of Out-of-Hospital Cardiac Arrest: A Nationwide Natural Experimental Study.

OBJECTIVES: This study aimed to investigate the effects of adding advanced cardiac life support (ACLS) training to an existing basic life support program and the operation of a designated team response for patients with out-of-hospital cardiac arrest (OHCA) on prehospital return of spontaneous circulation (ROSC) and ACLS management. METHODS: A natural experimental study was conducted for emergency medical service (EMS)-treated adult patients with OHCA in 2020. In 2019, a quarter of the EMS clinicians were trained in a 3-day ACLS courses, and they were designated to be dispatched first in suspected OHCA. Some were dispatched only to major emergencies, such as OHCA and myocardial infarction (dedicated team), while others were dispatched to all emergencies with priority to major ones (non-dedicated team). The exposure was the ambulance response type: dedicated, non-dedicated, and basic teams (others). The primary outcome was prehospital ROSC. The secondary outcomes were prehospital ACLS (advanced airway management and intravenous access). A multivariable logistic regression analysis was conducted to investigate the effect of ambulance response type on study outcomes. RESULTS: Among 23,512 eligible patients with OHCA, 54.8% (12,874) were treated by the basic team, 36.5% (8,580) by the non-dedicated ACLS team, and 8.8% (2,058) were treated by the dedicated ACLS team. Prehospital ROSC was greater for the designated team than for the basic team (dedicated ACLS team 13.8%, non-dedicated ACLS team 11.3%, and basic team 6.7%) (p < 0.01). In the final logistic regression analysis, compared with the basic team, the designated ACLS team was associated with a higher probability of prehospital ROSC (AOR (95% CIs), 1.88 (1.68-2.09) compared to the non-dedicated ACLS team, and 2.46 (2.09-2.90) compared to the dedicated ACLS team), prehospital advanced airway management (1.72 (1.57-1.87) and 1.73 (1.48-2.03), respectively), and intravenous access (2.29 (2.16-2.43) and 2.76 (2.50-3.04), respectively). CONCLUSION: Additional ACLS training and operation of a designated OHCA team response were associated with higher rates of prehospital ROSC and prehospital ACLS provision. However, further research is needed to find the optimal operation for EMS to improve survival outcomes.

Extracorporeal cardiopulmonary resuscitation location, coronary angiography and survival in out-of-hospital cardiac arrest.

INTRODUCTION: The best location for safe and timely implementation of extracorporeal cardiopulmonary resuscitation (ECPR) is currently uncertain. We aimed to evaluate the association between the location of ECPR and survival outcomes in out-of-hospital cardiac arrest (OHCA) patients. We also evaluated whether the effects of ECPR location on survival differed between patients who underwent coronary angiography (CAG) and those who did not. METHODS: We used data collected between 2013 and 2020 from a nationwide OHCA database. Adult OHCA patients with presumed cardiac etiology who underwent ECPR were included in the study. The primary outcome was survival to discharge. The main exposure was the ECPR location (emergency department [ED] or cardiac catheterization laboratory [Cath lab]). We compared primary outcomes of ECPR between the ED and Cath lab using multivariable logistic regression. The interaction between ECPR location and CAG was also evaluated. RESULTS: Of 564 ECPR patients, 448 (79.4%) and 116 (20.6%) underwent ECPR in the ED and Cath lab, respectively. CAG was observed in 52.5% and 72.4% of the patients in the ED and Cath lab groups, respectively. There were no significant differences in survival to discharge between the ED and Cath lab groups (14.1% vs. 12.9%, p = 0.75, adjusted odds ratio [AOR] [95% confidence interval] 1.87 [0.85-4.11]). AOR of interaction analysis (95% CI) for survival to discharge of the ED group was 2.34 (1.02-5.40) in patients with CAG and 0.28 (0.04-1.84) in patients without CAG (p for interaction was 0.04). CONCLUSION: In adult OHCA patients who underwent ECPR and CAG, ECPR in the ED shortened time to ECMO pump-on time and increased survival to discharge compared to ECPR in the Cath lab.

Efficacy of distance training program for cardiopulmonary resuscitation utilizing smartphone application and home delivery system.

AIM OF THE STUDY: Community cardiopulmonary resuscitation (CPR) education is important for laypersons. However, during the COVID-19 pandemic, with social distancing, conventional face-to-face CPR training was unavailable. We developed a distance learning CPR training course (HEROS-Remote) using a smartphone application that monitors real-time chest compression quality and a home delivery collection system for mannikins. This study aimed to evaluate the efficacy of the HEROS-Remote course by comparing chest compression quality with that of conventional CPR training. METHODS: We applied layperson CPR education with HEROS-Remote and conventional education in Seoul during the COVID-19 pandemic. Both groups underwent a 2-min post-training chest compression test, and we tested non-inferiority. Chest compression depth, rate, complete recoil, and composite chest compression score was measured. Trainees completed a satisfaction survey on CPR education and delivery. The primary outcome was the mean chest compression depth. RESULTS: A total of 180 trainees were enrolled, with 90 assigned to each training group. Chest compression depth of HEROS-Remote training showed non-inferiority to that of conventional training (67.4 vs. 67.8, p = 0.78), as well as composite chest compression score (92.7 vs. 95.5, p = 0.16). The proportions of adequate chest compression depth, chest compression rate, and chest compressions with complete chest recoil were similar in both training sessions. In the HEROS-Remote training, 90% of the trainees were satisfied with CPR training, and 96% were satisfied with the delivery and found it convenient. CONCLUSION: HEROS-Remote training was non-inferior to conventional CPR training in terms of chest compression quality. Distance learning CPR training using a smartphone application and mannikin delivery had high user satisfaction and was logistically feasible.

Thermal resistance of Escherichia coli O157:H7 in laboratory media, milk, and beef extracts during non-isothermal processing at various heating rates.

This study investigated the effect of non-isothermal treatments with different heating rates (HRs) on inactivating Escherichia coli O157:H7 in various heating media. E. coli O157:H7 in phosphate-buffered saline (pH 7; PBS), Luria-Bertani broth with (LBS) or without (LB) 1% NaCl, milk, 3% beef extract (beef3%), and 30% beef extract (beef30%) were inactivated under non-isothermal conditions (up to 50 - 60 °C) using various HRs between 1.32 and 10.78 °C/min. After treatment with an HR of 1.32 °C/min to a target temperature of 60 °C, the reduction level of E. coli O157:H7 were 6.49, 2.28, 1.20, 1.30, 5.55 and 5.02 log CFU/mL in PBS, LB, LBS, milk, beef3%, and beef30%, respectively. Contrastingly, E. coli O157:H7 treated in PBS, LB, milk, beef3%, and beef30% with an HR of 10.78 °C/min to the same target temperature were completely inactivated to not-detectable level. Moreover, E. coli O157:H7 treated at 10.63 °C/min exhibited more severe morphological injuries than those at 2.23 °C/min. Interestingly, inactivation through non-isothermal treatment is potentially involved in either ribonucleic acid or lipid synthesis, as E. coli O157:H7 treated at 10.63 °C/min for 3.5 min less recovered on TSA with rifampicin and streptomycin. These observations highlight the ability of the E. coli O157:H7 to survive for long periods at a potentially sub-lethal temperature, which may be enhanced concomitantly with a decrease in the HR of the non-isothermal treatment.

Risk Factors for the Prescription of Ineffective Antiviral Candidates for COVID-19 During the Early Pandemic Period in Korea.

BACKGROUND: Although the evidence of treatment for coronavirus disease 2019 (COVID-19) changed rapidly, little is known about the patterns of potential pharmacological treatment during the early period of the COVID-19 pandemic in Korea and the risk factors for ineffective prescription. METHODS: Using claims data from the Korean National Health Insurance System, this retrospective cohort study included admission episodes for COVID-19 from February to December 2020. Ineffective antiviral prescriptions for COVID-19 were defined as lopinavir/ritonavir (LPN/r) and hydroxychloroquine (HCQ) prescribed after July 2020, according to the revised National Institute of Health COVID-19 treatment guidelines. Factors associated with ineffective prescriptions, including patient and hospital factors, were identified by multivariate logistic regression analysis. RESULTS: Of the 15,723 COVID-19 admission episodes from February to June 2020, 4,183 (26.6%) included prescriptions of LPN/r, and 3,312 (21.1%) included prescriptions of HCQ. Of the 48,843 admission episodes from July to December 2020, after the guidelines were revised, 2,258 (4.6%) and 182 (0.4%) included prescriptions of ineffective LPN/r and HCQ, respectively. Patient factors independently associated with ineffective antiviral prescription were older age (adjusted odds ratio [aOR] per 10-year increase, 1.17; 95% confidence interval [CI], 1.14-1.20) and severe condition with an oxygen requirement (aOR, 2.49; 95% CI, 2.24-2.77). The prescription of ineffective antiviral drugs was highly prevalent in primary and nursing hospitals (aOR, 40.58; 95% CI, 31.97-51.50), public sector hospitals (aOR, 15.61; 95% CI, 12.76-19.09), and regions in which these drugs were highly prescribed before July 2020 (aOR, 10.65; 95% CI, 8.26-13.74). CONCLUSION: Ineffective antiviral agents were prescribed to a substantial number of patients during the first year of the COVID-19 pandemic in Korea. Treatment with these ineffective drugs tended to be prolonged in severely ill patients and in primary and public hospitals.

Neutralization Method of Ransomware Detection Technology Using Format Preserving Encryption.

Ransomware is one type of malware that involves restricting access to files by encrypting files stored on the victim's system and demanding money in return for file recovery. Although various ransomware detection technologies have been introduced, existing ransomware detection technologies have certain limitations and problems that affect their detection ability. Therefore, there is a need for new detection technologies that can overcome the problems of existing detection methods and minimize the damage from ransomware. A technology that can be used to detect files infected by ransomware and by measuring the entropy of files has been proposed. However, from an attacker's point of view, neutralization technology can bypass detection through neutralization using entropy. A representative neutralization method is one that involves decreasing the entropy of encrypted files by using an encoding technology such as base64. This technology also makes it possible to detect files that are infected by ransomware by measuring entropy after decoding the encoded files, which, in turn, means the failure of the ransomware detection-neutralization technology. Therefore, this paper derives three requirements for a more sophisticated ransomware detection-neutralization method from the perspective of an attacker for it to have novelty. These requirements are (1) it must not be decoded; (2) it must support encryption using secret information; and (3) the entropy of the generated ciphertext must be similar to that of plaintext. The proposed neutralization method satisfies these requirements, supports encryption without decoding, and applies format-preserving encryption that can adjust the input and output lengths. To overcome the limitations of neutralization technology using the encoding algorithm, we utilized format-preserving encryption, which could allow the attacker to manipulate the entropy of the ciphertext as desired by changing the expression range of numbers and controlling the input and output lengths in a very free manner. To apply format-preserving encryption, Byte Split, BinaryToASCII, and Radix Conversion methods were evaluated, and an optimal neutralization method was derived based on the experimental results of these three methods. As a result of the comparative analysis of the neutralization performance with existing studies, when the entropy threshold value was 0.5 in the Radix Conversion method, which was the optimal neutralization method derived from the proposed study, the neutralization accuracy was improved by 96% based on the PPTX file format. The results of this study provide clues for future studies to derive a plan to counter the technology that can neutralize ransomware detection technology.