Concurrent Infection with Clade 2.3.4.4b Highly Pathogenic Avian Influenza H5N6 and H5N1 Viruses, South Korea, 2023.

Highly pathogenic avian influenza H5N6 and H5N1 viruses of clade 2.3.4.4b were simultaneously introduced into South Korea at the end of 2023. An outbreak at a broiler duck farm consisted of concurrent infection by both viruses. Sharing genetic information and international surveillance of such viruses in wild birds and poultry is critical.

Pathogenicity of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Cats in Mice and Ferrets, South Korea, 2023.

The prevalence of highly pathogenic avian influenza (HPAI) A(H5N1) viruses has increased in wild birds and poultry worldwide, and concomitant outbreaks in mammals have occurred. During 2023, outbreaks of HPAI H5N1 virus infections were reported in cats in South Korea. The H5N1 clade 2.3.4.4b viruses isolated from 2 cats harbored mutations in the polymerase basic protein 2 gene encoding single amino acid substitutions E627K or D701N, which are associated with virus adaptation in mammals. Hence, we analyzed the pathogenicity and transmission of the cat-derived H5N1 viruses in other mammals. Both isolates caused fatal infections in mice and ferrets. We observed contact infections between ferrets, confirming the viruses had high pathogenicity and transmission in mammals. Most HPAI H5N1 virus infections in humans have occurred through direct contact with poultry or a contaminated environment. Therefore, One Health surveillance of mammals, wild birds, and poultry is needed to prevent potential zoonotic threats.

Hyperkalemia Detection in Emergency Departments Using Initial ECGs: A Smartphone AI ECG Analyzer vs. Board-Certified Physicians.

BACKGROUND: Hyperkalemia is a potentially fatal condition that mandates rapid identification in emergency departments (EDs). Although a 12-lead electrocardiogram (ECG) can indicate hyperkalemia, subtle changes in the ECG often pose detection challenges. An artificial intelligence application that accurately assesses hyperkalemia risk from ECGs could revolutionize patient screening and treatment. We aimed to evaluate the efficacy and reliability of a smartphone application, which utilizes camera-captured ECG images, in quantifying hyperkalemia risk compared to human experts. METHODS: We performed a retrospective analysis of ED hyperkalemic patients (serum potassium ≥ 6 mmol/L) and their age- and sex-matched non-hyperkalemic controls. The application was tested by five users and its performance was compared to five board-certified emergency physicians (EPs). RESULTS: Our study included 125 patients. The area under the curve (AUC)-receiver operating characteristic of the application's output was nearly identical among the users, ranging from 0.898 to 0.904 (median: 0.902), indicating almost perfect interrater agreement (Fleiss' kappa 0.948). The application demonstrated high sensitivity (0.797), specificity (0.934), negative predictive value (NPV) (0.815), and positive predictive value (PPV) (0.927). In contrast, the EPs showed moderate interrater agreement (Fleiss' kappa 0.551), and their consensus score had a significantly lower AUC of 0.662. The physicians' consensus demonstrated a sensitivity of 0.203, specificity of 0.934, NPV of 0.527, and PPV of 0.765. Notably, this performance difference remained significant regardless of patients' sex and age (P < 0.001 for both). CONCLUSION: Our findings suggest that a smartphone application can accurately and reliably quantify hyperkalemia risk using initial ECGs in the ED.

Ionic stress enhances ER-PM connectivity via phosphoinositide-associated SYT1 contact site expansion in Arabidopsis.

The interorganelle communication mediated by membrane contact sites (MCSs) is an evolutionary hallmark of eukaryotic cells. MCS connections enable the nonvesicular exchange of information between organelles and allow them to coordinate responses to changing cellular environments. In plants, the importance of MCS components in the responses to environmental stress has been widely established, but the molecular mechanisms regulating interorganelle connectivity during stress still remain opaque. In this report, we use the model plant Arabidopsis thaliana to show that ionic stress increases endoplasmic reticulum (ER)-plasma membrane (PM) connectivity by promoting the cortical expansion of synaptotagmin 1 (SYT1)-enriched ER-PM contact sites (S-EPCSs). We define differential roles for the cortical cytoskeleton in the regulation of S-EPCS dynamics and ER-PM connectivity, and we identify the accumulation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the PM as a molecular signal associated with the ER-PM connectivity changes. Our study highlights the functional conservation of EPCS components and PM phosphoinositides as modulators of ER-PM connectivity in eukaryotes, and uncovers unique aspects of the spatiotemporal regulation of ER-PM connectivity in plants.

A Retrospective Clinical Evaluation of an Artificial Intelligence Screening Method for Early Detection of STEMI in the Emergency Department.

BACKGROUND: Rapid revascularization is the key to better patient outcomes in ST-elevation myocardial infarction (STEMI). Direct activation of cardiac catheterization laboratory (CCL) using artificial intelligence (AI) interpretation of initial electrocardiography (ECG) might help reduce door-to-balloon (D2B) time. To prove that this approach is feasible and beneficial, we assessed the non-inferiority of such a process over conventional evaluation and estimated its clinical benefits, including a reduction in D2B time, medical cost, and 1-year mortality. METHODS: This is a single-center retrospective study of emergency department (ED) patients suspected of having STEMI from January 2021 to June 2021. Quantitative ECG (QCG™), a comprehensive cardiovascular evaluation system, was used for screening. The non-inferiority of the AI-driven CCL activation over joint clinical evaluation by emergency physicians and cardiologists was tested using a 5% non-inferiority margin. RESULTS: Eighty patients (STEMI, 54 patients [67.5%]) were analyzed. The area under the curve of QCG score was 0.947. Binned at 50 (binary QCG), the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 98.1% (95% confidence interval [CI], 94.6%, 100.0%), 76.9% (95% CI, 60.7%, 93.1%), 89.8% (95% CI, 82.1%, 97.5%) and 95.2% (95% CI, 86.1%, 100.0%), respectively. The difference in sensitivity and specificity between binary QCG and the joint clinical decision was 3.7% (95% CI, -3.5%, 10.9%) and 19.2% (95% CI, -4.7%, 43.1%), respectively, confirming the non-inferiority. The estimated median reduction in D2B time, evaluation cost, and the relative risk of 1-year mortality were 11.0 minutes (interquartile range [IQR], 7.3-20.0 minutes), 26,902.2 KRW (22.78 USD) per STEMI patient, and 12.39% (IQR, 7.51-22.54%), respectively. CONCLUSION: AI-assisted CCL activation using initial ECG is feasible. If such a policy is implemented, it would be reasonable to expect some reduction in D2B time, medical cost, and 1-year mortality.

Rare earth elements induce cytoskeleton-dependent and PI4P-associated rearrangement of SYT1/SYT5 endoplasmic reticulum-plasma membrane contact site complexes in Arabidopsis.

In plant cells, environmental stressors promote changes in connectivity between the cortical endoplasmic reticulum (ER) and the plasma membrane (PM). Although this process is tightly regulated in space and time, the molecular signals and structural components mediating these changes in interorganelle communication are only starting to be characterized. In this report, we confirm the presence of a putative tethering complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+- and lipid-binding protein 1 (CLB1/SYT7). This complex is enriched at ER-PM contact sites (EPCSs), has slow responses to changes in extracellular Ca2+, and displays severe cytoskeleton-dependent rearrangements in response to the trivalent lanthanum (La3+) and gadolinium (Gd3+) rare earth elements (REEs). Although REEs are generally used as non-selective cation channel blockers at the PM, here we show that the slow internalization of REEs into the cytosol underlies the activation of the Ca2+/calmodulin intracellular signaling, the accumulation of phosphatidylinositol-4-phosphate (PI4P) at the PM, and the cytoskeleton-dependent rearrangement of the SYT1/SYT5 EPCS complexes. We propose that the observed EPCS rearrangements act as a slow adaptive response to sustained stress conditions, and that this process involves the accumulation of stress-specific phosphoinositide species at the PM.

Nursing stress factors affecting turnover intention among hospital nurses.

AIMS: This study aimed to identify the nursing stress factors, which affect turnover intention in hospital nurses. BACKGROUND: Nursing stress is known to be an important predictor of turnover intention in nurses. Although nurses experience various sources of stress across work environments, cultures, and generations, little is known about the stress factors affecting turnover intention in nurses. DESIGN: A descriptive cross-sectional design was employed. METHODS: A total of 329 nurses were recruited through convenience sampling from 27 hospitals in South Korea. Data were collected from May to November 2018 using a questionnaire. RESULTS: Among the stress factors, stress from patients and their families, workload stress, stress from conflicts with supervisors, and stress from conflicts with peers were associated with turnover intention in hospital nurses. These variables explained 40.0% of the variance in turnover intention among hospital nurses. CONCLUSIONS: Stress from interpersonal relationships with patients and their families, supervisors, and peers may have a considerable impact on turnover intention. To reduce nursing turnover intention, coping strategies to reduce stress from patients and their families should be established. It is necessary to provide programmes that foster interpersonal relationship skills in the workplace. Nurse managers may encourage communication among nurses to establish positive relationships.

The relationship between spinal pain and temporomandibular joint disorders in Korea: a nationwide propensity score-matched study.

BACKGROUND: Patients with temporomandibular joint disorder (TMD) often complain of pain in other areas. Several studies have been conducted on spinal pain in TMD patients, but have contained only limited information. Therefore, this study analyzed the relationship between TMD and spinal pain in greater detail by using nationwide data. METHODS: A total of 12,375 TMD patients from the Korean National Health Insurance Review and Assessment database were analyzed. Controls were selected using propensity score-matching. The McNemar test, chi-square test, and paired t-test were used to compare the prevalence and severity of spinal pain between cases and matched controls. Logistic regression and linear regression models were used to analyze factors affecting the prevalence and severity of spinal pain in patients with TMD. RESULTS: The annual period prevalence of TMD was 1.1%. The prevalence was higher in younger individuals than in individuals of other ages and was higher in women than in men. The medical expenditure for TMD per person was $86. Among TMD patients, 2.5% underwent surgical procedures and 0.3% were hospitalized. The prevalence of spinal pain in patients with TMD was 48%, whereas that in the control group was 34%. Increased severity of TMD was associated with an increased probability of spinal pain. The medical expenditure, mean number of visits, and lengths of treatment for spinal pain were greater for patients with TMD than for controls ($136 vs. $81, 4.8 days vs. 2.7 days, 5.5 days vs. 3.3 days). Higher TMD grade was associated with greater differences in average medical expenditure, number of visits, and lengths of treatment for spinal pain between cases and controls. Additionally, for women, living in a rural area and having an older age and more severe TMD were associated with a greater probability of spinal pain and higher medical expenditure related to spinal pain. CONCLUSION: A strong association was observed between the presence of TMD and the presence of spinal pain. The association became stronger as the severity of TMD increased, indicating a positive correlation between the severity of TMD and spinal pain.

Highly Pathogenic Avian Influenza A(H5N6) in Domestic Cats, South Korea.

In December 2016, highly pathogenic avian influenza (HPAI) infection with systemic pathologic lesions was found in cats in South Korea. Genetic analyses indicated that the feline isolates were similar to HPAI H5N6 viruses isolated in chicken farms nearby. This finding highlights the need for monitoring of domestic mammals during HPAI outbreaks.

Surveillance of avian influenza viruses in South Korea between 2012 and 2014.

BACKGROUND: National surveillance of avian influenza virus (AIV) in South Korea has been annually conducted for the early detection of AIV and responses to the introduction of highly pathogenic avian influenza (HPAI) virus. In this study, we report on a nationwide surveillance study of AIV in domestic poultry and wild birds in South Korea between 2012 and 2014. METHODS: During the surveillance programs between 2012 and 2014, 141,560 samples were collected. Of these, 102,199 were from poultry farms, 8215 were from LBMs, and 31,146 were from wild bird habitats. The virus isolation was performed by inoculation of embryonated chicken eggs and AIV isolates were detected using hemagglutination assay. For subtying of AIV, the hemagglutinin and neuraminidase genes were confirmed by sequencing. Phylogenetic analysis of the H5 subtypes was performed using 28 H5 AIV isolates. RESULTS: Between 2012 and 2014, a total of 819 AIV were isolated from 141,560 samples. Virus isolation rates for AIV were 0.6, 0.4, 0.1, and 2.7% in wild birds (n = 202), domestic ducks (n = 387), minor poultry (n = 11), and the live bird market (LBM) (n = 219), respectively. In wild birds, various subtypes were found including H1-H7 and H9-H13. The major subtypes were H5 (n = 48, 23.9%: N3 (n = 4) and N8 (n = 44)), H4 (n = 39, 19.4%), and H1 (n = 29, 14.4%). In domestic poultry, mainly ducks, the H5N8 (n = 275, 59.3%), H3 (n = 30, 17.2%), and H6 (n = 53, 11.4%) subtypes were predominantly found. The most frequently detected subtypes in LBM, primarily Korean native chicken, were H9 (n = 169, 77.2%). H3 (n = 10, 4%) and H6 (n = 30, 13.7%) were also isolated in LBM. Overall, the prevalence of AIV was found to be higher between winter and spring and in western parts of South Korea. The unusual high prevalence of the H5 subtype of AIV was due to the large scale outbreak of H5N8 HPAI in wild birds and domestic poultry in 2014. CONCLUSIONS: Enhanced surveillance and application of effective control measures in wild birds and domestic poultry, including LBM, should be implemented to control AI and eradicate HPAI.

The Arabidopsis synaptotagmin1 is enriched in endoplasmic reticulum-plasma membrane contact sites and confers cellular resistance to mechanical stresses.

Eukaryotic endoplasmic reticulum (ER)-plasma membrane (PM) contact sites are evolutionarily conserved microdomains that have important roles in specialized metabolic functions such as ER-PM communication, lipid homeostasis, and Ca(2+) influx. Despite recent advances in knowledge about ER-PM contact site components and functions in yeast (Saccharomyces cerevisiae) and mammals, relatively little is known about the functional significance of these structures in plants. In this report, we characterize the Arabidopsis (Arabidopsis thaliana) phospholipid binding Synaptotagmin1 (SYT1) as a plant ortholog of the mammal extended synaptotagmins and yeast tricalbins families of ER-PM anchors. We propose that SYT1 functions at ER-PM contact sites because it displays a dual ER-PM localization, it is enriched in microtubule-depleted regions at the cell cortex, and it colocalizes with Vesicle-Associated Protein27-1, a known ER-PM marker. Furthermore, biochemical and physiological analyses indicate that SYT1 might function as an electrostatic phospholipid anchor conferring mechanical stability in plant cells. Together, the subcellular localization and functional characterization of SYT1 highlights a putative role of plant ER-PM contact site components in the cellular adaptation to environmental stresses.

Smoking cessation programmes using traditional medicine in Korea.

BACKGROUND: There are growing interests in using various methods including traditional and complementary medicines (T&CM) for tobacco control. The study aimed to introduce how traditional Korean medicine (TKM) applied to smoking cessation programmes in Korea and to show the detail information of each programme for designing other smoke cessation programmes. METHODS: Reports of the smoke cessation programmes in Korea were searched on March 10th, 2016, from the webpages of the related agencies and the databases: the Ministry of Health and Welfare, the Korea Health Foundation, the Association of Korean Medicine, PubMed, Google scholar, the RISS, the KISS, the NDSL, and the OASIS. Smoking cessation programmes, projects, or services using traditional Korean medicine (TKM) were included with no language, implementation site, and year restrictions. RESULTS: The three smoking cessation programmes using TKM in South Korea were the public health centre smoking cessation programme (PHC-SCP), the Ministry of Gender Equality & Family smoking cessation programme (MOGEF-SCP), and the National Health Insurance Service smoking cessation treatment project (NHIS-SCP). All programmes included ear acupuncture and counselling. Manual acupuncture was only used in the NHIS-SCP. The MOGEF-SCP and the NHIS-SCP used herbal medicines selectively. The PHC-SCP and MOGEF-SCP provided education programme and other tools such as non-smoking doll, self-writing handbook. They were run at no cost for participants. Treatment period were different for each programmes, 3 weeks, 4 weeks, 8 to 12 weeks, respectively. Treatment frequency was twice a week for PHC-SCP and MOGEF-SCP, and dependent on each clinic for NHIS-SCP. CONCLUSIONS: This study showed the summaries of the smoking cessation programme that used TKM. The three programmes and the detail information will be a reference for other countries that are going to apply T&CM to their smoking cessation programme. Though TKM integrated smoking cessation programmes had been contributed to stop smoking, persistent efforts are needed to develop more effective and various treatments. In addition, this study suggests that consistent support and systematic reporting system are needed to be successful in non-smoking strategy.

Experimental infection of SPF and Korean native chickens with highly pathogenic avian influenza virus (H5N8).

In 2014, an H5N8 outbreak of highly pathogenic avian influenza (HPAI) occurred in South Korea. The H5N8 strain produced mild to moderate clinical signs and mortality rates in commercial chicken farms, especially Korean native chicken farms. To understand the differences between their pathogenicity in SPF chicken and Korean native chicken., we evaluated the mean bird lethal doses (BLD50) of the Korean representative H5N8 virus (A/broiler duck/Korea/Buan2/2014) The BLD50values of the H5N8 virus were 10(5.3)EID50 and 10(6.7)EID50 in SPF and Korean native chickens, respectively. In addition, the mean death time was much longer, and the viral titers in tissues of H5N8-infected chickens were significantly lower, in the Korean group than in the SPF group. These features of the H5N8 virus likely account for its mild-to-moderate pathogenicity in commercial chicken farms, especially Korean native chicken flocks, despite the fact that it is a highly pathogenic virus according to the OIE criteria. To improve current understanding and management of HPAI, pathogenic characterization of novel emerging viruses should be performed by natural route in major poultry species in each country.

Arabidopsis guard cell integrity involves the epigenetic stabilization of the FLP and FAMA transcription factor genes.

Arabidopsis guard cell (GC) fate is conferred via a transient pulse of expression of FAMA that encodes a bHLH transcription factor. Stomata often function for years, suggesting that the FAMA expression window stabilizes long-term GC identity or that additional factors operate. Transgenic lines harboring a copy of a FAMA transgene were found to induce the fate resetting of mature GCs to that of lineage-specific stem cells causing new stomata to arise within shells of the old, a Stoma-in-Stoma (SIS) phenotype. These lines disrupt the normal trimethylation on lysine 27 of histone3 (H3K27me3) on stomatal stem cell genes, a phenotype rescued by constitutive expression of the Polycomb Group (PcG) gene CURLY LEAF. Thus the stability of stomatal fate is enforced by a PcG-mediated reduction in the transcriptional accessibility of stem cell genes and by the endogenous FAMA gene itself. Moreover, a transgenic FOUR LIPS gene, which encodes a MYB protein that is not required for GC fate, also induces a SIS phenotype and disrupts H3K27 trimethylation. Thus FLP might indirectly enforce GC fate as well.

Deep functional redundancy between FAMA and FOUR LIPS in stomatal development.

Functional redundancy arises between gene paralogs as well as non-homologous genes that play a common role at a shared node. The bHLH transcription factor FAMA, along with the paralogous MYB genes, FOUR LIPS (FLP) and MYB88 all ensure that Arabidopsis stomata contain just two guard cells (GCs) by enforcing a single symmetric precursor cell division before stomatal maturity. Consistent with this function, FLP and FAMA exhibit the same expression pattern in which both translational GFP fusions emit fluorescence just before and after symmetric division; however, FAMA but not FLP is required to confer GC fate. Strikingly, swapping the genes and promoters of the FLP and FAMA genes results in the reciprocal complementation of respective loss-of-function mutants. Thus, an FLP transgene can restore GC fate to a fama mutant background. FAMA, FLP and the FLP paralog MYB88 were previously shown to influence higher order functions in stomatal development, including maintaining and stabilizing stomatal fate. Here we show that these overlapping functions are likely to also involve interactions between FLP and FAMA with the RETINOBLASTOMA-RELATED (RBR) protein.

Novel reassortant influenza A(H5N8) viruses among inoculated domestic and wild ducks, South Korea, 2014.

An outbreak of highly pathogenic avian influenza, caused by a novel reassortant influenza A (H5N8) virus, occurred among poultry and wild birds in South Korea in 2014. The aim of this study was to evaluate the pathogenesis in and mode of transmission of this virus among domestic and wild ducks. Three of the viruses had similar pathogenicity among infected domestic ducks: the H5N8 viruses were moderately pathogenic (0%-20% mortality rate); in wild mallard ducks, the H5N8 and H5N1 viruses did not cause severe illness or death; viral replication and shedding were greater in H5N8-infected mallards than in H5N1-infected mallards. Identification of H5N8 viruses in birds exposed to infected domestic ducks and mallards indicated that the viruses could spread by contact. We propose active surveillance to support prevention of the spread of this virus among wild birds and poultry, especially domestic ducks.

Pathologic Changes in Wild Birds Infected with Highly Pathogenic Avian Influenza A(H5N8) Viruses, South Korea, 2014.

In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus.

Developmental regulation of CYCA2s contributes to tissue-specific proliferation in Arabidopsis.

In multicellular organisms, morphogenesis relies on a strict coordination in time and space of cell proliferation and differentiation. In contrast to animals, plant development displays continuous organ formation and adaptive growth responses during their lifespan relying on a tight coordination of cell proliferation. How developmental signals interact with the plant cell-cycle machinery is largely unknown. Here, we characterize plant A2-type cyclins, a small gene family of mitotic cyclins, and show how they contribute to the fine-tuning of local proliferation during plant development. Moreover, the timely repression of CYCA2;3 expression in newly formed guard cells is shown to require the stomatal transcription factors FOUR LIPS/MYB124 and MYB88, providing a direct link between developmental programming and cell-cycle exit in plants. Thus, transcriptional downregulation of CYCA2s represents a critical mechanism to coordinate proliferation during plant development.

The FOUR LIPS and MYB88 transcription factor genes are widely expressed in Arabidopsis thaliana during development.

PREMISE OF THE STUDY: The FOUR LIPS (FLP) and MYB88 transcription factors, which are closely related in structure and function, control the development of stomata, as well as entry into megasporogenesis in Arabidopsis thaliana. However, other locations where these transcription factors are expressed are poorly described. Documenting additional locations where these genes are expressed might define new functions for these genes. METHODS: Expression patterns were examined throughout vegetative and reproductive development. The expression from two transcriptional-reporter fusions were visualized with either ß-glucuronidase (GUS) or green fluorescence protein (GFP). KEY RESULTS: Both flp and myb88 genes were expressed in many, previously unreported locations, consistent with the possibility of additional functions for FLP and MYB88. Moreover, expression domains especially of FLP display sharp cutoffs or boundaries. CONCLUSIONS: In addition to stomatal and reproductive development, FLP and MYB88, which are R2R3 MYB transcription factor genes, are expressed in many locations in cells, tissues, and organs.