Genetic organization of an M protein trans-acting positive regulator (Mga) orthologue and its adjacent M-like protein (SCM) alleles in Streptococcus canis.

OBJECTIVE: The purpose of this study was to identify the M protein trans-acting positive regulator (Mga) orthologue and its adjacent M-like protein (SCM) alleles in Streptococcus canis. RESULTS: Using the 39 SCM allele isolates and polymerase chain reaction-based amplification and sequencing, we obtained the deduced Mga amino acid (AA) sequences. The 22 Mga sequences in whole-genome sequences were obtained by searching the National Collection of Type Cultures 12,191(T) Mga sequence into the database. The percentage identity to the type-strain Mga sequence was examined along with its size. The presence of the Mga-specific motifs was confirmed. Of the 62 strains, we identified 59 Mga sequences with an AA size of 509 (except for four different sizes). Percentage identity ranged from 96.66 to 100% with the confirmed Mga-specific motifs and diverse SCM allele populations. Our findings support the presence of an Mga orthologue and diverse SCM allele populations.

Trends in the detection of viruses causing gastroenteritis over a 10-year period and impact of nonpharmaceutical interventions.

BACKGROUND: Viral gastroenteritis continues to be a leading cause of death in low-income countries. The impact of nonpharmaceutical interventions (NPIs) on the transmission of gastroenteritis-causing viruses during the COVID-19 pandemic is understudied. OBJECTIVES: To investigate the 10-year trends of enteric viruses and estimate the impact of implementing and mitigating NPIs. STUDY DESIGN: Data regarding norovirus, rotavirus, adenovirus, astrovirus, and sapovirus detection were collected from five Korean hospitals between January 2013 and April 2023. We compared positivity between the pre-pandemic, pandemic, and post-pandemic periods. The causal effects of implementing and mitigating NPIs were quantified using the Bayesian Structural Time Series (BSTS) model. RESULTS: Norovirus was most frequently detected (9.9 %), followed by rotavirus (6.7 %), adenovirus (3.3 %), astrovirus (1.4 %), and sapovirus (0.6 %). During the pandemic, the positivity of all five viruses decreased, ranging from -1.0 % to -8.1 %, with rotavirus showing the greatest decrease. In the post-pandemic period, positivity rebounded for all viruses except for rotavirus. The BSTS model revealed that NPI implementation negatively affected the detection of all five viruses, resulting in reductions ranging from -73.0 % to -91.0 % compared to the prediction, with rotavirus being the least affected. Conversely, NPI mitigation positively affected the detection of all viruses, ranging from 79.0 % to 200.0 %, except for rotavirus. CONCLUSIONS: Trends observed over 10 years show that NPIs have had a major impact on changes in enteric virus detection. The effect of vaccines, in addition to NPIs, on rotavirus detection requires further investigation. Our findings emphasize the importance of NPIs in infection control and prevention.

Anticoagulation in patients with end-stage kidney disease and atrial fibrillation: a national population-based study.

Background: The prevalence of atrial fibrillation (AF) in patients with end-stage kidney disease (ESKD) is high and increasing. However, evidence regarding oral anticoagulant (OAC) use in these patients is insufficient and conflicting. Methods: This retrospective cohort study included patients in the Korea National Health Insurance System diagnosed with AF after ESKD onset from January 2007 to December 2017. The primary outcome was all-cause death. Secondary outcomes were ischaemic stroke, hospitalization for major bleeding and major adverse cardiovascular events (MACE). Outcomes were compared between OAC users and non-users using 6-month landmark analysis and 1:3 propensity score matching (PSM). Results: Among patients with ESKD and AF, the number of prescribed OACs increased 2.3-fold from 2012 (n = 3579) to 2018 (n = 8341) and the proportion of direct OACs prescribed increased steadily from 0% in 2012 to 51.4% in 2018. After PSM, OAC users had a lower risk of all-cause death {hazard ratio [HR] 0.67 [95% confidence interval (CI) 0.55-0.81]}, ischaemic stroke [HR 0.61 (95% CI 0.41-0.89)] and MACE [HR 0.70 (95% CI 0.55-0.90)] and no increased risk of hospitalization for major bleeding [HR 0.99 (95% CI 0.72-1.35)] compared with non-users. Unlike warfarin, direct OACs were associated with a reduced risk of all-cause death and hospitalization for major bleeding. Conclusions: In patients with ESKD and AF, OACs were associated with reduced all-cause death, ischaemic stroke and MACE.

The mediating role of the left ventricular mass index on the relationship between the fluid balance and left ventricular diastolic function in patients with chronic kidney disease.

BACKGROUND: The pathophysiological mechanism of cardiovascular disease in patients with chronic kidney disease (CKD) is complicated. Mediation analysis is an important statistical tool for gaining insight into the complex mechanisms of exposure-outcome effects. We investigated the potential mediating role of the left ventricular mass index (LVMI) on the association between fluid balance (overhydration/extracellular water, OH/ECW) and left ventricular diastolic function (E/e´ ratio) in patients with CKD not yet on dialysis. METHODS: Bioimpedance spectroscopy, echocardiography, and laboratory evaluations were performed on 425 consecutive patients on the same day. The patients were classified into two groups according to the estimated glomerular filtration rate corresponding to CKD stages 3 and 5. Mediation analysis was performed using the PROCESS macro and bootstrapping methods. RESULTS: OH/ECW and LVMI were positively correlated with the E/e´ ratio in both the CKD stages 3 and five groups. In CKD stage 5, there was a statistically significant association between OH/ECW and LVMI, whereas no correlation was observed in CKD stage 3. In the mediation analysis, LVMI positively mediated the relationship between OH/ECW and E/e´ ratio when controlling for confounders in patients with CKD stage 5 (B = 2.602; Boot 95% confidence interval, 1.313-4.076). CONCLUSION: In our analysis, the indirect effect of mediators was significant in patients with advanced CKD. Therefore, our study suggests that further research on several other risk factors may be needed to determine the underlying mechanisms of association between the associated factors in all CKD stages.

The moderating effect of fluid overload on the relationship between the augmentation index and left ventricular diastolic function in patients with CKD.

Increased vascular stiffness, fluid overload, and left ventricular diastolic dysfunction (LVDD) are common in patients with chronic kidney disease (CKD). We investigated the potential moderating effect of volume status in the relationship between arterial stiffness and left ventricular (LV) diastolic function in non-dialysis patients with stage 5 CKD. The radial augmentation index at a heart rate of 75 beats/min (rAIx75), overhydration/extracellular water (OH/ECW), and E/e´ ratio were concurrently measured in 152 consecutive patients. Each of these parameters reflects the status of vascular stiffness, fluid balance, and LV diastolic function, respectively. Hierarchical regression analysis demonstrated a significant interaction effect of OH/ECW for all patients (P = 0.015), even after controlling for confounders. In separate analyses, this interaction effect was particularly significant in women (P = 0.010), whereas its significance in patients with diabetes was marginally significant (P = 0.062). Our study suggested that fluid overload could be one of the more aggravating factors of LVDD in patients with CKD who have increased arterial stiffness. Therefore, it is advisable to conduct simultaneous assessments of vascular stiffness, fluid balance, and LV function, particularly in the specific groups mentioned earlier. Our results may serve as evidence applicable to patients with chronic heart failure.

Development of fluorescence-linked immunosorbent assay for rapid detection of Staphylococcus aureus.

Staphylococcus aureus is a major pathogen that causes infections and life-threatening diseases. Although antibiotics, such as methicillin, have been used, methicillin-resistant S. aureus (MRSA) causes high morbidity and mortality rates, and conventional detection methods are difficult to be used because of time-consuming process. To control the spread of S. aureus, a development of a rapid and simple detection method is required. In this study, we generated a fluorescent anti-S. aureus antibody, and established a novel fluorescence-linked immunosorbent assay (FLISA)-based S. aureus detection method. The method showed high sensitivity and low limit of detection toward MRSA detection. The assay time for FLISA was 5 h, which was faster than that of conventional enzyme-linked immunosorbent assay (ELISA) or rapid ELISA. Moreover, the FLISA-based detection method was applied to diagnose clinically isolated MRSA samples that required only 5.3 h of preincubation. The FLISA method developed in this study can be widely applied as a useful tool for convenient S. aureus detection. KEY POINTS: • A fluorescence-linked immunosorbent assay-based S. aureus detection method • Simultaneous quantification of a maximum of 96 samples within 5 h • Application of the novel system to diagnosis clinical isolates.

A Methylazanediyl Bisacetamide Derivative Sensitizes Staphylococcus aureus Persisters to a Combination of Gentamicin And Daptomycin.

Infections caused by Staphylococcus aureus, notably methicillin-resistant S. aureus (MRSA), pose treatment challenges due to its ability to tolerate antibiotics and develop antibiotic resistance. The former, a mechanism independent of genetic changes, allows bacteria to withstand antibiotics by altering metabolic processes. Here, a potent methylazanediyl bisacetamide derivative, MB6, is described, which selectively targets MRSA membranes over mammalian membranes without observable resistance development. Although MB6 is effective against growing MRSA cells, its antimicrobial activity against MRSA persisters is limited. Nevertheless, MB6 significantly potentiates the bactericidal activity of gentamicin against MRSA persisters by facilitating gentamicin uptake. In addition, MB6 in combination with daptomycin exhibits enhanced anti-persister activity through mutual reinforcement of their membrane-disrupting activities. Crucially, the "triple" combination of MB6, gentamicin, and daptomycin exhibits a marked enhancement in the killing of MRSA persisters compared to individual components or any double combinations. These findings underscore the potential of MB6 to function as a potent and selective membrane-active antimicrobial adjuvant to enhance the efficacy of existing antibiotics against persister cells. The molecular mechanisms of MB6 elucidated in this study provide valuable insights for designing anti-persister adjuvants and for developing new antimicrobial combination strategies to overcome the current limitations of antibiotic treatments.

Performance Evaluation of the Roche Cobas 5800 HBV and HCV Tests: Comparison of the 200 and 500 µL Protocols.

Background: Clinical management of patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) relies on the viral load (VL). The Cobas 5800 system (Roche Diagnostics) can determine VLs in 200 and 500 µL samples, but the performance of each protocol has not been compared. We evaluated the performance of both protocols for the HBV and HCV tests. Methods: Precision and linearity were verified using commercial panels. Probit analyses were used to determine limits of detection (LoDs). The results obtained with 336 samples were compared using the 200 and 500 µL protocols. Data from 6,737 retrospective HBV and 768 HCV samples were compared to estimate the effects of the different LoDs on the diagnostic results of the protocols. Correlations between protocols were tested with Spearman's rank correlation coefficients (rho). Results: The precision and linearity of both protocols were verified. The LoDs for the 200 and 500 µL protocols were 6.5 and 2.7 IU/mL for HBV and 29.7 and 8.2 IU/mL for HCV, respectively. The agreement between the protocols ranged from 0.8 to 1.0. The results obtained with the HBV and HCV tests showed a strong correlation (rho=0.994). Only 0.4% of HBV and 0.4% of HCV test results were affected by the LoDs of the 200 µL protocol. Conclusions: The Cobas 5800 200 and 500 µL protocols for the HBV DNA and HCV RNA tests demonstrated excellent performance. These findings establish the 200 µL protocol as a new option for low-volume samples, especially for pediatric and difficult-to-bleed patients.

Bypassing Heaven's Gate Technique Using Black-Box Testing.

In recent years, the number and sophistication of malware attacks on computer systems have increased significantly. One technique employed by malware authors to evade detection and analysis, known as Heaven's Gate, enables 64-bit code to run within a 32-bit process. Heaven's Gate exploits a feature in the operating system that allows the transition from a 32-bit mode to a 64-bit mode during execution, enabling the malware to evade detection by security software designed to monitor only 32-bit processes. Heaven's Gate poses significant challenges for existing security tools, including dynamic binary instrumentation (DBI) tools, widely used for program analysis, unpacking, and de-virtualization. In this paper, we provide a comprehensive analysis of the Heaven's Gate technique. We also propose a novel approach to bypass the Heaven's Gate technique using black-box testing. Our experimental results show that the proposed approach effectively bypasses and prevents the Heaven's Gate technique and strengthens the capabilities of DBI tools in combating advanced malware threats.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Effective methods for monitoring internal contamination among workers handling radioactive materials in various fields.

This study aimed to develop effective methods for monitoring internal contamination among workers handling radioactive materials in various fields. A total of 160 workers from nuclear power plants, medical institutions, military units, and educational/research institutions were included in the study. The monitoring methods included urinalysis and whole-body counting (WBC) using a mobile radio bioassay laboratory (MRL). Gamma-emitting radionuclides were monitored using the MRL WBC system, and a separate pretreatment procedure was used for tritium measurement in urine samples. Gross beta-screening was performed using a liquid scintillation counting system. The results were evaluated on the basis of the established screening criteria and compared with the dose limits. Additionally, tritium concentrations in the bodies of workers in the vicinity of a heavy-water reactor was analysed to assess the association between tritium concentration and occupation. The results showed a wide distribution of tritium concentrations. Workers involved in fuel and maintenance tasks demonstrated the maximum exposure. Workers in medical facilities showed low levels of internal contamination, which was primarily related to tasks involving radioactive isotopes. Military personnel involved in equipment repair showed significant tritium contamination due to damage during repairs. Workers in educational and research institutions in general had low levels of internal contamination.

A strategy to promote the convenient storage and direct use of polyhydroxybutyrate-degrading Bacillus sp. JY14 by lyophilization with protective reagents.

BACKGROUND: Bioplastics are attracting considerable attention, owing to the increase in non-degradable waste. Using microorganisms to degrade bioplastics is a promising strategy for reducing non-degradable plastic waste. However, maintaining bacterial viability and activity during culture and storage remains challenging. With the use of conventional methods, cell viability and activity was lost; therefore, these conditions need to be optimized for the practical application of microorganisms in bioplastic degradation. Therefore, we aimed to optimize the feasibility of the lyophilization method for convenient storage and direct use. In addition, we incoporated protective reagents to increase the viability and activity of lyophilized microorganisms. By selecting and applying the best protective reagents for the lyophilization process and the effects of additives on the growth and PHB-degrading activity of strains were analyzed after lyophilization. For developing the lyophilization method for protecting degradation activity, it may promote practical applications of bioplastic-degrading bacteria. RESULTS: In this study, the polyhydroxybutyrate (PHB)-degrading strain, Bacillus sp. JY14 was lyophilized with the use of various sugars as protective reagents. Among the carbon sources tested, raffinose was associated with the highest cell survival rate (12.1%). Moreover, 7% of raffionose showed the highest PHB degradation yield (92.1%). Therefore, raffinose was selected as the most effective protective reagent. Also, bacterial activity was successfully maintained, with raffinose, under different storage temperatures and period. CONCLUSIONS: This study highlights lyophilization as an efficient microorganism storage method to enhance the applicability of bioplastic-degrading bacterial strains. The approach developed herein can be further studied and used to promote the application of microorganisms in bioplastic degradation.

Molecular Determinants of ß-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus (MRSA): An Updated Review.

The development of antibiotic resistance in Staphylococcus aureus, particularly in methicillin-resistant S. aureus (MRSA), has become a significant health concern worldwide. The acquired mecA gene encodes penicillin-binding protein 2a (PBP2a), which takes over the activities of endogenous PBPs and, due to its low affinity for ß-lactam antibiotics, is the main determinant of MRSA. In addition to PBP2a, other genetic factors that regulate cell wall synthesis, cell signaling pathways, and metabolism are required to develop high-level ß-lactam resistance in MRSA. Although several genetic factors that modulate ß-lactam resistance have been identified, it remains unclear how they alter PBP2a expression and affect antibiotic resistance. This review describes the molecular determinants of ß-lactam resistance in MRSA, with a focus on recent developments in our understanding of the role of mecA-encoded PBP2a and on other genetic factors that modulate the level of ß-lactam resistance. Understanding the molecular determinants of ß-lactam resistance can aid in developing novel strategies to combat MRSA.

Variant Analysis of the Thymidine Kinase and DNA Polymerase Genes of Herpes Simplex Virus in Korea: Frequency of Acyclovir Resistance Mutations.

The thymidine kinase (TK) and DNA polymerase (pol) genes of the herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are two important genes involved in antiviral resistance. We investigated the genetic polymorphisms of the HSV-TK and pol genes in clinical isolates from Korean HSV-infected patients using next-generation sequencing (NGS) for the first time in Korea. A total of 81 HSV-1 and 47 HSV-2 isolates were examined. NGS was used to amplify and sequence the TK and pol genes. Among the 81 HSV-1 isolates, 12 and 17 natural polymorphisms and 9 and 23 polymorphisms of unknown significance in TK and pol were found, respectively. Two HSV-1 isolates (2.5%) exhibited the E257K amino acid substitution in TK, associated with antiviral resistance. Out of 47 HSV-2 isolates, 8 natural polymorphisms were identified in TK, and 9 in pol, with 13 polymorphisms of unknown significance in TK and 10 in pol. No known resistance-related mutations were observed in HSV-2. These findings contribute to our understanding of the genetic variants associated with antiviral resistance in HSV-1 and HSV-2 in Korea, with frequencies of known antiviral resistance-related mutations of 2.5% and 0% in HSV-1 and HSV-2, respectively.

Comparing Left Ventricular Diastolic Function between Peritoneal Dialysis and Non-Dialysis Patients with Stage 5 Chronic Kidney Disease: A Propensity Score-Matched Analysis.

Patients with chronic kidney disease (CKD) have a high incidence of left ventricular diastolic dysfunction (LVDD), which increases the risk of heart failure and mortality. We assessed fluid overload as an independent risk factor for LVDD in patients with decreased kidney function and compared its impact on the E/e' ratio as a parameter for assessing left ventricular diastolic functions between patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and those with non-dialysis CKD stage 5 (CKD5) using propensity score matching (PSM). After PSM, 222 patients (CAPD, n = 111; CKD5, n = 111) were included. Fluid balance was assessed using bio-impedance spectroscopy and LVDD was determined by echocardiography based on an E/e' ratio of >15. The CKD5 group had a significantly higher E/e' ratio (p = 0.002), while fluid overload (OH/ECW) did not differ significantly between the groups. In the CAPD group, there were no significant differences in OH/ECW between patients with and without LVDD (p = 0.517). However, in the CKD5 group, patients with LVDD showed a significantly higher OH/ECW (p = 0.001). In a regression analysis investigating factors associated with the E/e' ratio, OH/ECW was not significantly associated with the E/e' ratio in the CAPD group (p = 0.087), but in the CKD5 group, it was independently correlated (p = 0.047). The factors closely associated with LVDD varied depending on dialysis dependence. While fluid overload independently influenced LVDD in non-dialysis patients, it was not statistically significant in patients with CAPD. Early assessment and management of volume status are crucial in addressing LVDD in patients with advanced-stage CKD.

Evaluation of the BD Phoenix CPO Detect Panel for Detection and Classification of Carbapenemase Producing Enterobacterales.

Carbapenem-resistant Enterobacterales (CRE) pose a serious public health threat due to their resistance to most antibiotics. Rapid and correct detection of carbapenemase producing organisms (CPOs) can help inform clinician decision making on antibiotic therapy. The BD Phoenix™ CPO detect panel, as part of antimicrobial susceptibility testing (AST), detects carbapenemase activity (P/N) and categorizes CPOs according to Ambler classes. We evaluated a CPO detect panel against 109 carbapenemase producing Enterobacterales (CPE) clinical isolates from Korea. The panel correctly detected carbapenemases production in 98.2% (n = 107/109) isolates and identified 78.8% (n = 26/33) class A, 65.9% (n = 29/44) class B, and 56.3% (n = 18/32) class D carbapenemase producers as harboring their corresponding Ambler classes. Specifically, the panel correctly classified 81.3% (n = 13/16) of K. pneumoniae KPC isolates to class A. However, the panel failed to classify 40.0% (n = 4/10) IMP and 63.6% (n = 7/11) VIM isolates to class B. Despite 27.5% (n = 30/109) CPE not being assigned Ambler classes, all of them tested carbapenemase positive. Our results demonstrate that the CPO detect panel is a sensitive test for detecting CPE and classifying KPC as class A, helping with antibiotics selection, but one-third of CPE remained unclassified for Ambler classes.

Exploration of Potential Breath Biomarkers of Chronic Kidney Disease through Thermal Desorption-Gas Chromatography/Mass Spectrometry.

Breath volatile organic compound (VOC) analysis is a non-invasive tool for assessing health status; the compositional profile of these compounds in the breath of patients with chronic kidney disease is believed to change with decreasing renal function. We aimed to identify breath VOCs for recognizing patients with chronic kidney disease. Using thermal desorption-gas chromatography/mass spectrometry, untargeted analysis of breath markers was performed using breath samples of healthy controls (n = 18) versus non-dialysis (n = 21) and hemodialysis (n = 12) patients with chronic kidney disease in this cross-sectional study. A total of 303 VOCs alongside 12 clinical variables were used to determine the breath VOC profile. Metabolomic analysis revealed that age, systolic blood pressure, and fifty-eight breath VOCs differed significantly between the chronic kidney disease group (non-dialysis + hemodialysis) and healthy controls. Thirty-six VOCs and two clinical variables that showed significant associations with chronic kidney disease in the univariate analysis were further analyzed. Different spectra of breath volatile organic compounds between the control and chronic kidney disease groups were obtained. A multivariate model incorporating age, 2-methyl-pentane, and cyclohexanone showed high performance (accuracy, 86%) in identifying patients with chronic kidney disease with odds ratios of 0.18 (95% CI, 0.07-2.49, p = 0.013); 2.10 (0.94-2.24, p = 0.025); and 2.31 (0.88-2.64, p = 0.008), respectively. Hence, this study showed that renal dysfunction induces a characteristic profile of breath VOCs that can be used as non-invasive potential biomarkers in screening tests for CKD.

Biotypic and genotypic diversity in Pasteurella canis isolated from host animals and humans: differences in trehalose fermentation and nucleotide sequences encoding trehalose-6-phosphate hydrolase (treC).

The biotypic and genotypic features of Pasteurella canis isolated from dogs, cats, and humans were clarified by repetitive sequence-based fingerprinting and nucleotide sequences encoding trehalose-6-phosphate hydrolase (treC). Thirty P. canis and 48 P. multocida isolates were collected from dogs, cats, and humans to perform biotyping. The genotyping of P. canis by fingerprinting was followed by dendrogram construction. The whole-genome sequences (WGSs) were searched for the enzyme-coding nucleotide sequences around the main and adjacent loci constituting the operon. Full-length nucleotide sequences encoding the enzyme were determined using polymerase chain reaction and direct sequencing. Biotypic results were compared to the dendrogram and nucleotide sequence data. We observed a difference in trehalose fermentation with a positivity rate of 46.7%. Two (A-1/A-2) and three (B-1/B-2/B-3) clades were located on the dendrograms generated based on two repetitive sequence-based fingerprinting techniques, showing no association between trehalose fermentation and the clades. Based on the WGSs, two variants of the gene, namely, a 1,641 bp gene treC and a pseudogene (1,335 bp) of treC with its first 306 nucleotides deleted, were observed. Trehalose-positive isolates harbored treC, whereas trehalose-negative isolates lacked treC with or without the pseudogene. Our observations suggest biotypic and genotypic diversity among the P. canis isolates from animal and human hosts, with respect to trehalose fermentation and treC nucleotide sequences. This is the first report on the diversity of treC nucleotide sequences among these isolates.

Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Melatonin and Prostate Cancer: Anti-tumor Roles and Therapeutic Application.

Melatonin is an endogenous indoleamine that has been shown to inhibit tumor growth in laboratory models of prostate cancer. Prostate cancer risk has additionally been associated with exogenous factors that interfere with normal pineal secretory activity, including aging, poor sleep, and artificial light at night. Therefore, we aim to expand on the important epidemiological evidence, and to review how melatonin can impede prostate cancer. More specifically, we describe the currently known mechanisms of melatonin-mediated oncostasis in prostate cancer, including those that relate to the indolamine's ability to modulate metabolic activity, cell cycle progression and proliferation, androgen signaling, angiogenesis, metastasis, immunity and oxidative cell status, apoptosis, genomic stability, neuroendocrine differentiation, and the circadian rhythm. The outlined evidence underscores the need for clinical trials to determine the efficacy of supplemental, adjunct, and adjuvant melatonin therapy for the prevention and treatment of prostate cancer.